medalphabetМедицинский алфавитMedical alphabet2078-56312949-2807ООО «Альфмед»10.33667/2078-5631-2024-19-9-15medalphabet-3886Research ArticleСтатьиМолекулярные механизмы действия ДИМ и его клиническое применениеMolecular mechanisms of action of DIM and its clinical applicationhttps://orcid.org/0000-0003-3220-0333НикитинаЕ. А.NikitinaE. A.

Никитина Елена Александровна, к. м. н., доцент кафедры диетологии и клинической нутрициологии; научный сотрудник; эксперт Методического аккредитационно-симуляционного центра

Москва

Nikitina Elena A., PhD Med, associate professor at Dept of Dietetics and ClinicalNutrition; Research Fellow; Expert of the Methodological Accreditation andSimulation Center

Moscow

nikitina-ea1@rudn.ruhttps://orcid.org/0000-0002-4689-3591ОрловаС. В.OrlovaS. V.

Орлова Светлана Владимировна, д. м. н., проф., зав. кафедрой диетологии и клинической нутрициологии; главный научный сотрудник

Москва

Orlova Svetlana V., DM Sci (habil.), professor, head of Dept of Dieteticsand Clinical Nutritiology; Chief Researcher

Moscow

orlova-sv@rudn.ruhttps://orcid.org/0000-0003-0928-2131БатышеваТ. Т.BatyshevaT. T.

Батышева Татьяна Тимофеевна, глав. внештатный детский специалист невролог ДЗМ, глав. внештатный детский специалист по медицинской реабилитации Минздрава России, зав. кафедрой неврологии, физической, реабилитационной медицины и психологии детского возраста; д. м. н., проф., заслуженный врач РФ, директор

Москва

Batysheva Tatyana T., chief pediatric neurologist of the Health Dept of the City of Moscow, chief pediatric specialist in medical rehabilitation of the Ministry of Health of the Russian Federation, head of Dept of Neurology, Physical, Rehabilitation Medicine and Psychology of Childhood; DM Sci (habil.), professor, Honored Doctor of the Russian Federation, director

Moscow

https://orcid.org/0000-0002-0548-3414БалашоваН. В.BalashovaN. V.

Балашова Наталья Валерьевна, к. б. н., доцент кафедры диетологии и клинической нутрициологии; доцент кафедры клинической лабораторной диагностики факультета усовершенствования врачей

Author ID: 832745

Москва

Balashova Natalya V., PhD Bio Sci, assistant professor at Dept of Dietetics and Clinical Nutritiology; assistant professor at Dept of Clinical Laboratory Diagnostics of the Faculty of Advanced Training of Doctors

Author ID: 832745

Moscow

BalashovaN77@mail.ruhttps://orcid.org/0000-0001-8448-8493АлексееваМ. В.AlekseevaM. V.

Алексеева Марина Валерьевна, к. м. н., зам. директора по организационно-методической работе

Москва

Alekseeva Marina.V., PhD Med, deputy director for Organizational and Methodological Work

Moscow

https://orcid.org/0000-0002-5203-1082ВодолазкаяА. Н.VodolazkayaA. N.

Водолазкая Ангелина Николаевна, врач-диетолог

Москва

Vodolazkaya Angelina N., dietitian

Moscow

drvodolazkaya@gmail.comhttps://orcid.org/0000-0002-3811-9459ПрокопенкоЕ. В.ProkopenkoE. V.

Прокопенко Елена Валерьевна, врач-эндокринолог, диетолог, руководитель отдела развития и сопровождения медицинских информационных систем и сервисов

Москва

Prokopenko Elena V., endocrinologist, dietitian

Moscow

elvprokopenko@gmail.comhttps://orcid.org/0000-0001-8744-2976МагомедоваХ. А.MagomedovaKh. A.

Магомедова Хадижат Абдулхаликовна, провизор, генеральный директор

Москва

Magomedova Khadizhat A., provizor, general director

Moscow

hadiga28@mail.ruФГАОУ ВО «Российский университет дружбы народов» имени Патриса Лумумбы» (РУДН); ГБУЗ «Научно-практический центр детской психоневрологии Департамента здравоохранения г. Москвы»; ФГБУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава РоссииРоссияPeoples’ Friendship University of Russia named after Patrice Lumumba; Scientific and Practical Center for Pediatric Psychoneurology of the Moscow Department of Health; National Medical Research Center for Therapy and Preventive MedicineRussian FederationФГАОУ ВО «Российский университет дружбы народов» имени Патриса Лумумбы» (РУДН); ГБУЗ «Научно-практический центр детской психоневрологии Департамента здравоохранения г. Москвы»РоссияPeoples’ Friendship University of Russia named after Patrice Lumumba; Scientific and Practical Center for Pediatric Psychoneurology of the Moscow Department of HealthRussian FederationФГАОУ ВО «Российский университет дружбы народов» имени Патриса Лумумбы» (РУДН); ФГБУ «Национальный медицинский исследовательский центр терапии и профилактической медицины» Минздрава РоссииРоссияPeoples’ Friendship University of Russia named after Patrice Lumumba; National Medical Research Center for Therapy and Preventive MedicineRussian FederationАвстрийская клиника микронутриентной терапии BiogenaРоссияAustrian Clinic of Micronutrient Therapy BiogenaRussian FederationООО «ИНВИТРО»РоссияINVITRO LLCRussian FederationООО «Такем энд Ко»РоссияLtd Takem & CoRussian Federation202430102024019Современная гинекология (2)915Copyright © Никитина Е.А., Орлова С.В., Батышева Т.Т., Балашова Н.В., Алексеева М.В., Водолазкая А.Н., Прокопенко Е.В., Магомедова Х.А., 20242024Никитина Е.А., Орлова С.В., Батышева Т.Т., Балашова Н.В., Алексеева М.В., Водолазкая А.Н., Прокопенко Е.В., Магомедова Х.А.Nikitina E.A., Orlova S.V., Batysheva T.T., Balashova N.V., Alekseeva M.V., Vodolazkaya A.N., Prokopenko E.V., Magomedova K.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.med-alphabet.com/jour/article/view/3886

Оптимальное питание предусматривает необходимость и обязательность полного обеспечения потребностей организма не только в энергии, макро- и микронутриентах, но и в минорных биологически активных веществах. Одними из наиболее перспективных хемопротекторов являются глюкозинолаты и их активные производные, такие как 3,3’-дииндолилметан (ДИМ). ДИМ обладает способностью тормозить развитие и прогрессирование неоплазии за счет регуляции множества внутриклеточных сигнальных путей. В настоящее время проводится изучение клинической эффективности ДИМ при раке молочной железы и простаты, а также исследуется возможность применения антиоксидантных и противовоспалительных свойств ДИМ при нейродегенеративных, метаболических и иммунных заболеваниях.

Optimal nutrition requires complete provision of the human needs not only for energy, macro- and micronutrients, but also for minor biologically active substances. Some of the most promising chemoprotectors are glucosinolates and their active derivatives, such as 3,3’-diindolylmethane (DIM). DIM has the ability to inhibit the development and progression of neoplasia by regulating multiple intracellular signaling pathways. Currently, the clinical efficacy of DIM is being studied in breast and prostate cancer, and the possibility of using DIM’s antioxidant and anti-inflammatory properties in neurodegenerative, metabolic and immune diseases is being investigated.

33’-дииндолилметан (ДИМ)рак молочной железырак простатыхемопротекция33’-diindolylmethane (DIM)breast cancerprostate cancerchemoprotectionReferencesNoncommunicable diseases. WHO. https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseasesNoncommunicable diseases. WHO. https://www.who.int/news-room/fact-sheets/detail/noncommunicable-diseasesРак молочной железы. Информационные бюллетени ВОЗ. 13 марта 2024 г. https://www.who.int/ru/news-room/fact-sheets/detail/breast-cancer.Breast cancer. World Health Organization (WHO). 13 March 2024 https://www.who.int/news-room/fact-sheets/detail/breast-cancerЗдравоохранение в России. 2023: Стат. сб. Росстат. М., 2023. 179 с. https://rosstat.gov.ru/storage/mediabank/Zdravoohran-2023.pdf.Healthcare in Russia. 2023: Statistical Collection/Rosstat. M., 2023. 179 p. https://rosstat.gov.ru/storage/mediabank/Zdravoohran-2023.pdfМетодические рекомендации МР 2.3.1.0253–21 «Нормы физиологических потребностей в энергии и пищевых веществах для различных групп населения Российской Федерации», утверждены руководителем Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека – Главным государственным санитарным врачом Российской Федерации 22.07.2021. https://www.rospotrebnadzor.ru/documents/details.phpELEMENT_ID=1897.Methodical recommendations MR 2.3.1.0253–21 “Norms of physiological requirements in energy and nutrients of various groups of the population of the Russian Federation”, approved by the Head of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing Chief State Sanitary Physician of the Russian Federation 22.07.2021. (In Russ.). https://www.rospotrebnadzor.ru/documents/details.php?ELEMENT_ID=18979Kim Y, Je Y. Tea consumption and the risks of all-cause, cardiovascular disease, and cancer mortality: a meta-analysis of 38 prospective cohort data sets. Epidemiol Health. 2024 Jun; 21: e2024056. DOI: 10.4178/epih.e2024056Kim Y, Je Y. Tea consumption and the risks of all-cause, cardiovascular disease, and cancer mortality: a meta-analysis of 38 prospective cohort data sets. Epidemiol Health. 2024 Jun; 21: e2024056. DOI: 10.4178/epih.e2024056Wang K, Li Z, He J. Association of caffeine consumption with all-cause and cause-specific mortality in adult Americans with hypertension. Food Sci Nutr. 2024 Mar 8; 12 (6): 4185–4195. DOI: 10.1002/fsn3.4079Wang K, Li Z, He J. Association of caffeine consumption with all-cause and cause-specific mortality in adult Americans with hypertension. Food Sci Nutr. 2024 Mar 8; 12 (6): 4185–4195. DOI: 10.1002/fsn3.4079Borghi C, Tsioufis K, Agabiti-Rosei E, Burnier M, Cicero AFG, Clement D, Coca A, Desideri G, Grassi G, Lovic D, Lurbe E, Kahan T, Kreutz R, Jelakovic B, Polonia J, Redon J, Van De Borne P, Mancia G. Nutraceuticals and blood pressure control: a European Society of Hypertension position document. J. Hypertens. 2020 May; 38 (5): 799–812. DOI: 10.1097/HJH.0000000000002353Borghi C, Tsioufis K, Agabiti-Rosei E, Burnier M, Cicero AFG, Clement D, Coca A, Desideri G, Grassi G, Lovic D, Lurbe E, Kahan T, Kreutz R, Jelakovic B, Polonia J, Redon J, Van De Borne P, Mancia G. Nutraceuticals and blood pressure control: a European Society of Hypertension position document. J. Hypertens. 2020 May; 38 (5): 799–812. DOI: 10.1097/HJH.0000000000002353Chan KY, Wong MMH, Pang SSH, Lo KKH. Dietary supplementation for gestational diabetes prevention and management: a meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2021 Jun; 303 (6): 1381–1391. DOI: 10.1007/s00404‑021‑06023‑9Chan KY, Wong MMH, Pang SSH, Lo KKH. Dietary supplementation for gestational diabetes prevention and management: a meta-analysis of randomized controlled trials. Arch Gynecol Obstet. 2021 Jun; 303 (6): 1381–1391. DOI: 10.1007/s00404‑021‑06023‑9Guan R, Van Le Q, Yang H, Zhang D, Gu H, Yang Y, Sonne C, Lam SS, Zhong J, Jianguang Z, Liu R, Peng W. A review of dietary phytochemicals and their relation to oxidative stress and human diseases. Chemosphere. 2021 May; 271: 129499. DOI: 10.1016/j.chemosphere.2020.129499Guan R, Van Le Q, Yang H, Zhang D, Gu H, Yang Y, Sonne C, Lam SS, Zhong J, Jianguang Z, Liu R, Peng W. A review of dietary phytochemicals and their relation to oxidative stress and human diseases. Chemosphere. 2021 May; 271: 129499. DOI: 10.1016/j.chemosphere.2020.129499Osadnik T, Goławski M, Lewandowski P, Morze J, Osadnik K, Pawlas N, Lejawa M, Jakubiak GK, Mazur A, Schwingschackl L, Gąsior M, Banach M. A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults. Pharmacol Res. 2022 Sep; 183: 106402. DOI: 10.1016/j.phrs.2022.106402Osadnik T, Goławski M, Lewandowski P, Morze J, Osadnik K, Pawlas N, Lejawa M, Jakubiak GK, Mazur A, Schwingschackl L, Gąsior M, Banach M. A network meta-analysis on the comparative effect of nutraceuticals on lipid profile in adults. Pharmacol Res. 2022 Sep; 183: 106402. DOI: 10.1016/j.phrs.2022.106402Rosell M, Fadnes LT. Vegetables, fruits, and berries – a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res. 2024 Jan 25; 68. DOI: 10.29219/fnr.v68.10455Rosell M, Fadnes LT. Vegetables, fruits, and berries – a scoping review for Nordic Nutrition Recommendations 2023. Food Nutr Res. 2024 Jan 25; 68. DOI: 10.29219/fnr.v68.10455Rodríguez-Negrete EV, Morales-González Á, Madrigal-Santillán EO, Sánchez-Reyes K, Álvarez-González I, Madrigal-Bujaidar E, Valadez-Vega C, Chamorro-Cevallos G, Garcia-Melo LF, Morales-González JA. Phytochemicals and Their Usefulness in the Maintenance of Health. Plants (Basel). 2024 Feb 15; 13 (4): 523. DOI: 10.3390/plants13040523Rodríguez-Negrete EV, Morales-González Á, Madrigal-Santillán EO, Sánchez-Reyes K, Álvarez-González I, Madrigal-Bujaidar E, Valadez-Vega C, Chamorro-Cevallos G, Garcia-Melo LF, Morales-González JA. Phytochemicals and Their Usefulness in the Maintenance of Health. Plants (Basel). 2024 Feb 15; 13 (4): 523. DOI: 10.3390/plants13040523Sazali S, Badrin S, Norhayati MN, Idris NS. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis. BMJ Open. 2021 Jan 5; 11 (1): e039358. DOI: 10.1136/bmjopen‑2020–039358Sazali S, Badrin S, Norhayati MN, Idris NS. Coenzyme Q10 supplementation for prophylaxis in adult patients with migraine-a meta-analysis. BMJ Open. 2021 Jan 5; 11 (1): e039358. DOI: 10.1136/bmjopen‑2020–039358An P, Wan S, Luo Y, Luo J, Zhang X, Zhou S, Xu T, He J, Mechanick JI, Wu WC, Ren F, Liu S. Micronutrient Supplementation to Reduce Cardiovascular Risk. J. Am. Coll. Cardiol. 2022 Dec 13; 80 (24): 2269–2285. DOI: 10.1016/j.jacc.2022.09.048An P, Wan S, Luo Y, Luo J, Zhang X, Zhou S, Xu T, He J, Mechanick JI, Wu WC, Ren F, Liu S. Micronutrient Supplementation to Reduce Cardiovascular Risk. J. Am. Coll. Cardiol. 2022 Dec 13; 80 (24): 2269–2285. DOI: 10.1016/j.jacc.2022.09.048Moretti C, Bonomi M, Dionese P, Federici S, Fulghesu AM, Giannelli J, Giordano R, Guccione L, Maseroli E, Moghetti P, Mioni R, Pivonello R, Sabbadin C, Scaroni C, Tonacchera M, Verde N, Vignozzi L, Gambineri A. Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-Women’s Endocrinology. J. Endocrinol Invest. 2024 Jul 15. DOI: 10.1007/s40618–024–02363-wMoretti C, Bonomi M, Dionese P, Federici S, Fulghesu AM, Giannelli J, Giordano R, Guccione L, Maseroli E, Moghetti P, Mioni R, Pivonello R, Sabbadin C, Scaroni C, Tonacchera M, Verde N, Vignozzi L, Gambineri A. Inositols and female reproduction disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-Women’s Endocrinology. J. Endocrinol Invest. 2024 Jul 15. DOI: 10.1007/s40618–024–02363-wWei P, Liu M, Chen Y, Chen DC. Systematic review of soy isoflavone supplements on osteoporosis in women. Asian Pac J. Trop Med. 2012 Mar; 5 (3): 243–8. DOI: 10.1016/S 1995–7645 (12) 60033‑9Wei P, Liu M, Chen Y, Chen DC. Systematic review of soy isoflavone supplements on osteoporosis in women. Asian Pac J. Trop Med. 2012 Mar; 5 (3): 243–8. DOI: 10.1016/S 1995–7645 (12) 60033‑9Singla RK, Wang X, Gundamaraju R, Joon S, Tsagkaris C, Behzad S, Khan J, Gautam R, Goyal R, Rakmai J, Dubey AK, Simal-Gandara J, Shen B. Natural products derived from medicinal plants and microbes might act as a game-changer in breast cancer: a comprehensive review of preclinical and clinical studies. Crit Rev Food Sci Nutr. 2023 Nov; 63 (33): 11880–11924. DOI: 10.1080/10408398.2022.2097196Singla RK, Wang X, Gundamaraju R, Joon S, Tsagkaris C, Behzad S, Khan J, Gautam R, Goyal R, Rakmai J, Dubey AK, Simal-Gandara J, Shen B. Natural products derived from medicinal plants and microbes might act as a game-changer in breast cancer: a comprehensive review of preclinical and clinical studies. Crit Rev Food Sci Nutr. 2023 Nov; 63 (33): 11880–11924. DOI: 10.1080/10408398.2022.2097196Steinbrecher A, Linseisen J. Dietary intake of individual glucosinolates in participants of the EPIC-Heidelberg cohort study. Ann Nutr Metab. 2009; 54 (2): 87–96. DOI: 10.1159/000209266Steinbrecher A, Linseisen J. Dietary intake of individual glucosinolates in participants of the EPIC-Heidelberg cohort study. Ann Nutr Metab. 2009; 54 (2): 87–96. DOI: 10.1159/000209266Reyes-Hernández OD, Figueroa-González G, Quintas-Granados LI, Gutiérrez-Ruíz SC, Hernández-Parra H, Romero-Montero A, Del Prado-Audelo ML, Bernal-Chavez SA, Cortés H, Peña-Corona SI, Kiyekbayeva L, Ateşşahin DA, Goloshvili T, Leyva-Gómez G, Sharifi-Rad J. 3,3’-Diindolylmethane and indole‑3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways. Cancer Cell Int. 2023 Aug 26; 23 (1): 180. DOI: 10.1186/s12935‑023‑03031‑4Reyes-Hernández OD, Figueroa-González G, Quintas-Granados LI, Gutiérrez-Ruíz SC, Hernández-Parra H, Romero-Montero A, Del Prado-Audelo ML, Bernal-Chavez SA, Cortés H, Peña-Corona SI, Kiyekbayeva L, Ateşşahin DA, Goloshvili T, Leyva-Gómez G, Sharifi-Rad J. 3,3’-Diindolylmethane and indole‑3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways. Cancer Cell Int. 2023 Aug 26; 23 (1): 180. DOI: 10.1186/s12935‑023‑03031‑4Денисова Е. Л., Королев А. А., Никитенко Е. И., Кирпиченкова Е. В., Фетисов Р. Н., Козлов В. В., Онищенко Г. Г. Гигиеническая оценка содержания индолов в рационе студентов медицинского университета. Вопр. питания. 2018. Т. 87, № 6. С. 22–27. DOI: 10.24411/00 42–88 33‑2018‑10063 https://pubmed.ncbi.nlm.nih.gov/30763487Denisova E. L., Korolev A. A., Nikitenko E. I., Kirpichenkova E. V., Fetisov R. N., Kozlov V. V., Onishchenko G. G. Hygienic assessment of indoles in the diet of medical students. Voprosy pitaniia [Problems of Nutrition]. 2018; 87 (6): 22–7. DOI: 10.24411/0042‑8833‑2018‑10063 (in Russ.) Available at: https://pubmed.ncbi.nlm.nih.gov/30763487Ramakrishna K, Jain SK, Krishnamurthy S. Pharmacokinetic and Pharmacodynamic Properties of Indole‑3-carbinol in experimental focal ischemic Injury. Eur. J. Drug Metab Pharmacokinet. 2022 DOI: 10.1007/s13318–022–00771-yRamakrishna K, Jain SK, Krishnamurthy S. Pharmacokinetic and Pharmacodynamic Properties of Indole‑3-carbinol in experimental focal ischemic Injury. Eur. J. Drug Metab Pharmacokinet. 2022 DOI: 10.1007/s13318–022–00771-yWilliams DE. Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole‑3-Carbinol and 3,3’-Diindolylmethane. Front Nutr. 2021 Oct 1; 8: 734334. DOI: 10.3389/fnut.2021.734334Williams DE. Indoles Derived From Glucobrassicin: Cancer Chemoprevention by Indole‑3-Carbinol and 3,3’-Diindolylmethane. Front Nutr. 2021 Oct 1; 8: 734334. DOI: 10.3389/fnut.2021.734334Diindolylmethane (DIM) Information Resource Center. An Initiative of Faculty Members and Research Fellows at the University of California at Berkeley https://www.diindolylmethane-dim.com/references.htmDiindolylmethane (DIM) Information Resource Center. An Initiative of Faculty Members and Research Fellows at the University of California at Berkeley https://www.diindolylmethane-dim.com/references.htmCentofanti F, Buono A, Verboni M, Tomino C, Lucarini S, Duranti A, Pandolfi PP, Novelli G. Synthetic Methodologies and Therapeutic Potential of Indole‑3-Carbinol (I3C) and Its Derivatives. Pharmaceuticals (Basel). 2023 Feb 5; 16 (2): 240. DOI: 10.3390/ph16020240Centofanti F, Buono A, Verboni M, Tomino C, Lucarini S, Duranti A, Pandolfi PP, Novelli G. Synthetic Methodologies and Therapeutic Potential of Indole‑3-Carbinol (I3C) and Its Derivatives. Pharmaceuticals (Basel). 2023 Feb 5; 16 (2): 240. DOI: 10.3390/ph16020240Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016 Jul; 74 (7): 432–43. DOI: 10.1093/nutrit/nuw010Thomson CA, Ho E, Strom MB. Chemopreventive properties of 3,3-diindolylmethane in breast cancer: evidence from experimental and human studies. Nutr Rev. 2016 Jul; 74 (7): 432–43. DOI: 10.1093/nutrit/nuw010Li F, Xu Y, Chen C, Chen SM, Xiao BK, Tao ZZ. Pro-apoptotic and anti-proliferative effects of 3,3’-diindolylmethane in nasopharyngeal carcinoma cells via downregulation of telomerase activity. Mol Med Rep. 2015 Sep; 12 (3): 3815–3820. DOI: 10.3892/mmr.2015.3836Li F, Xu Y, Chen C, Chen SM, Xiao BK, Tao ZZ. Pro-apoptotic and anti-proliferative effects of 3,3’-diindolylmethane in nasopharyngeal carcinoma cells via downregulation of telomerase activity. Mol Med Rep. 2015 Sep; 12 (3): 3815–3820. DOI: 10.3892/mmr.2015.3836Herz C, Tran HTT, Landerer S, Gaus J, Schlotz N, Lehr L, Schäfer WR, Treeck O, Odongo GA, Skatchkov I, Lamy E. Normal human immune cells are sensitive to telomerase inhibition by Brassica-derived 3,3-diindolylmethane, partly mediated via ERα/β-AP1 signaling. Mol Nutr Food Res. 2017 Sep; 61 (9). DOI: 10.1002/mnfr.201600524Herz C, Tran HTT, Landerer S, Gaus J, Schlotz N, Lehr L, Schäfer WR, Treeck O, Odongo GA, Skatchkov I, Lamy E. Normal human immune cells are sensitive to telomerase inhibition by Brassica-derived 3,3-diindolylmethane, partly mediated via ERα/β-AP1 signaling. Mol Nutr Food Res. 2017 Sep; 61 (9). DOI: 10.1002/mnfr.201600524Kong D, Banerjee S, Huang W, Li Y, Wang Z, Kim HR, Sarkar FH. Mammalian target of rapamycin repression by 3,3’-diindolylmethane inhibits invasion and angiogenesis in platelet-derived growth factor-D-overexpressing PC 3 cells. Cancer Res. 2008 Mar 15; 68 (6): 1927–34. DOI: 10.1158/0008–5472.CAN‑07–3241Kong D, Banerjee S, Huang W, Li Y, Wang Z, Kim HR, Sarkar FH. Mammalian target of rapamycin repression by 3,3’-diindolylmethane inhibits invasion and angiogenesis in platelet-derived growth factor-D-overexpressing PC 3 cells. Cancer Res. 2008 Mar 15; 68 (6): 1927–34. DOI: 10.1158/0008–5472.CAN‑07–3241Chang X, Tou JC, Hong C, Kim HA, Riby JE, Firestone GL, Bjeldanes LF. 3,3’-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis. 2005 Apr; 26 (4): 771–8. DOI: 10.1093/carcin/bgi018Chang X, Tou JC, Hong C, Kim HA, Riby JE, Firestone GL, Bjeldanes LF. 3,3’-Diindolylmethane inhibits angiogenesis and the growth of transplantable human breast carcinoma in athymic mice. Carcinogenesis. 2005 Apr; 26 (4): 771–8. DOI: 10.1093/carcin/bgi018Kim EJ, Shin M, Park H, Hong JE, Shin HK, Kim J, Kwon DY, Park JH. Oral administration of 3,3’-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. J. Nutr. 2009 Dec; 139 (12): 2373–9. DOI: 10.3945/jn.109.111864.Kim EJ, Shin M, Park H, Hong JE, Shin HK, Kim J, Kwon DY, Park JH. Oral administration of 3,3’-diindolylmethane inhibits lung metastasis of 4T1 murine mammary carcinoma cells in BALB/c mice. J. Nutr. 2009 Dec; 139 (12): 2373–9. DOI: 10.3945/jn.109.111864.Li WX, Chen LP, Sun MY, Li JT, Liu HZ, Zhu W. 3'3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling. Oncotarget. 2015 Sep 15; 6 (27): 23776–92. DOI: 10.18632/oncotarget.4196Li WX, Chen LP, Sun MY, Li JT, Liu HZ, Zhu W. 3'3-Diindolylmethane inhibits migration, invasion and metastasis of hepatocellular carcinoma by suppressing FAK signaling. Oncotarget. 2015 Sep 15; 6 (27): 23776–92. DOI: 10.18632/oncotarget.4196Munakarmi S, Shrestha J, Shin HB, Lee GH, Jeong YJ. 3,3’-Diindolylmethane Suppresses the Growth of Hepatocellular Carcinoma by Regulating Its Invasion, Migration, and ER Stress-Mediated Mitochondrial Apoptosis. Cells. 2021 May 12; 10 (5): 1178. DOI: 10.3390/cells10051178Munakarmi S, Shrestha J, Shin HB, Lee GH, Jeong YJ. 3,3’-Diindolylmethane Suppresses the Growth of Hepatocellular Carcinoma by Regulating Its Invasion, Migration, and ER Stress-Mediated Mitochondrial Apoptosis. Cells. 2021 May 12; 10 (5): 1178. DOI: 10.3390/cells10051178Tsao CW, Li JS, Lin YW, Wu ST, Cha TL, Liu CY. Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3’-diindolylmethane in an enzalutamide-resistant prostate cancer cell line. Sci Rep. 2021 Jan 13; 11 (1): 1239. DOI: 10.1038/s41598‑020‑80519‑3Tsao CW, Li JS, Lin YW, Wu ST, Cha TL, Liu CY. Regulation of carcinogenesis and mediation through Wnt/β-catenin signaling by 3,3’-diindolylmethane in an enzalutamide-resistant prostate cancer cell line. Sci Rep. 2021 Jan 13; 11 (1): 1239. DOI: 10.1038/s41598‑020‑80519‑3Zhu P, Yu H, Zhou K, Bai Y, Qi R, Zhang S. 3,3’-Diindolylmethane modulates aryl hydrocarbon receptor of esophageal squamous cell carcinoma to reverse epithelial-mesenchymal transition through repressing RhoA/ROCK1-mediated COX2/PGE 2 pathway. J Exp Clin Cancer Res. 2020 Jun 16;39(1):113. DOI: 10.1186/s13046–020–01618–7.)Zhu P, Yu H, Zhou K, Bai Y, Qi R, Zhang S. 3,3’-Diindolylmethane modulates aryl hydrocarbon receptor of esophageal squamous cell carcinoma to reverse epithelial-mesenchymal transition through repressing RhoA/ROCK1-mediated COX2/PGE 2 pathway. J Exp Clin Cancer Res. 2020 Jun 16;39(1):113. DOI: 10.1186/s13046–020–01618–7.)Amarakoon D, Lee WJ, Tamia G, Lee SH. Indole‑3-Carbinol: Occurrence, Health-Beneficial Properties, and Cellular/Molecular Mechanisms. Annu Rev Food Sci Technol. 2023 Mar 27; 14: 347–366. DOI: 10.1146/annurev-food‑060721–025531Amarakoon D, Lee WJ, Tamia G, Lee SH. Indole‑3-Carbinol: Occurrence, Health-Beneficial Properties, and Cellular/Molecular Mechanisms. Annu Rev Food Sci Technol. 2023 Mar 27; 14: 347–366. DOI: 10.1146/annurev-food‑060721–025531Jayakumar P, Pugalendi KV, Sankaran M. Attenuation of hyperglycemia-mediated oxidative stress by indole‑3-carbinol and its metabolite 3, 3’- diindolylmethane in C 57BL/6J mice. J. Physiol Biochem. 2014 Jun; 70 (2): 525–34. DOI: 10.1007/s13105‑014‑0332‑5Jayakumar P, Pugalendi KV, Sankaran M. Attenuation of hyperglycemia-mediated oxidative stress by indole‑3-carbinol and its metabolite 3, 3’- diindolylmethane in C 57BL/6J mice. J. Physiol Biochem. 2014 Jun; 70 (2): 525–34. DOI: 10.1007/s13105‑014‑0332‑5Опыт применения индинола при папилломавирусной инфекции: сб. статей. – М., 2011. – 50 с. https://indinol.ru/assets/files/Sbornik_VPH_A4_out.pdfExperience in the use of indinol in papillomavirus infection: Sat. articles. Мoscow, 2011. 50 pp. (In Russ.). Available at: https://indinol.ru/assets/files/Sbornik_VPH_A4_out.pdfNikitina D, Llacuachaqui M, Sepkovic D, Bradlow HL, Narod SA, Kotsopoulos J. The effect of oral 3,3’-diindolylmethane supplementation on the 2:16α-OHE ratio in BRCA1 mutation carriers. Fam Cancer. 2015 Jun; 14 (2): 281–6. DOI: 10.1007/s10689‑015‑9783‑2Nikitina D, Llacuachaqui M, Sepkovic D, Bradlow HL, Narod SA, Kotsopoulos J. The effect of oral 3,3’-diindolylmethane supplementation on the 2:16α-OHE ratio in BRCA1 mutation carriers. Fam Cancer. 2015 Jun; 14 (2): 281–6. DOI: 10.1007/s10689‑015‑9783‑2Godínez-Martínez E, Santillán R, Sámano R, Chico-Barba G, Tolentino MC, Hernández-Pineda J. Effectiveness of 3,3’-Diindolylmethane Supplements on Favoring the Benign Estrogen Metabolism Pathway and Decreasing Body Fat in Premenopausal Women. Nutr Cancer. 2023; 75 (2): 510–519. DOI: 10.1080/01635581.2022.2123535Godínez-Martínez E, Santillán R, Sámano R, Chico-Barba G, Tolentino MC, Hernández-Pineda J. Effectiveness of 3,3’-Diindolylmethane Supplements on Favoring the Benign Estrogen Metabolism Pathway and Decreasing Body Fat in Premenopausal Women. Nutr Cancer. 2023; 75 (2): 510–519. DOI: 10.1080/01635581.2022.2123535Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004; 50 (2): 161–7. DOI: 10.1207/s15327914nc5002_5Dalessandri KM, Firestone GL, Fitch MD, Bradlow HL, Bjeldanes LF. Pilot study: effect of 3,3’-diindolylmethane supplements on urinary hormone metabolites in postmenopausal women with a history of early-stage breast cancer. Nutr Cancer. 2004; 50 (2): 161–7. DOI: 10.1207/s15327914nc5002_5Green T, See J, Schauch M, Reil J, Glover M, Brix J, Gerry A, Li K, Newman M, Gahler RJ, Wood S. A randomized, double-blind, placebo-controlled, cross-over trial to evaluate the effect of EstroSense® on 2-hydroxyestrone:16α-hydroxyestrone ratio in premenopausal women. J. Complement Integr Med. 2022 Oct 6; 20 (1): 199–206. DOI: 10.1515/jcim‑2022–0301Green T, See J, Schauch M, Reil J, Glover M, Brix J, Gerry A, Li K, Newman M, Gahler RJ, Wood S. A randomized, double-blind, placebo-controlled, cross-over trial to evaluate the effect of EstroSense® on 2-hydroxyestrone:16α-hydroxyestrone ratio in premenopausal women. J. Complement Integr Med. 2022 Oct 6; 20 (1): 199–206. DOI: 10.1515/jcim‑2022–0301Thomson CA, Chow HHS, Wertheim BC, Roe DJ, Stopeck A, Maskarinec G, Altbach M, Chalasani P, Huang C, Strom MB, Galons JP, Thompson PA. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res Treat. 2017 Aug; 165 (1): 97–107. DOI: 10.1007/s10549‑017‑4292‑7Thomson CA, Chow HHS, Wertheim BC, Roe DJ, Stopeck A, Maskarinec G, Altbach M, Chalasani P, Huang C, Strom MB, Galons JP, Thompson PA. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res Treat. 2017 Aug; 165 (1): 97–107. DOI: 10.1007/s10549‑017‑4292‑7Yerushalmi R, Bargil S, Ber Y, Ozlavo R, Sivan T, Rapson Y, Pomerantz A, Tsoref D, Sharon E, Caspi O, Grubsrein A, Margel D. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial. Carcinogenesis. 2020 Oct 15; 41 (10): 1395–1401. DOI: 10.1093/carcin/bgaa050Yerushalmi R, Bargil S, Ber Y, Ozlavo R, Sivan T, Rapson Y, Pomerantz A, Tsoref D, Sharon E, Caspi O, Grubsrein A, Margel D. 3,3-Diindolylmethane (DIM): a nutritional intervention and its impact on breast density in healthy BRCA carriers. A prospective clinical trial. Carcinogenesis. 2020 Oct 15; 41 (10): 1395–1401. DOI: 10.1093/carcin/bgaa050Сайт «Международная ассоциация по патологии шейки матки и кольпоскопии». URL: https://ifcpc.org/ the International Federation of colposcopy and cervical pathology. https://ifcpc.orgСайт «Международная ассоциация по патологии шейки матки и кольпоскопии». URL: https://ifcpc.org/ the International Federation of colposcopy and cervical pathology. https://ifcpc.orgXue L, Pestka JJ, Li M, Firestone GL, Bjeldanes LF. 3,3’-Diindolylmethane stimulates murine immune function in vitro and in vivo. J. Nutr Biochem. 2008 May; 19 (5): 336–44. DOI: 10.1016/j.jnutbio.2007.05.004Xue L, Pestka JJ, Li M, Firestone GL, Bjeldanes LF. 3,3’-Diindolylmethane stimulates murine immune function in vitro and in vivo. J. Nutr Biochem. 2008 May; 19 (5): 336–44. DOI: 10.1016/j.jnutbio.2007.05.004Verma V, Sharma V, Singh V, Sharma S, Bishnoi AK, Chandra V, Maikhuri JP, Dwivedi A, Kumar A, Gupta G. Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells. Toxicol Appl Pharmacol. 2014 Oct 15; 280 (2): 323–34. DOI: 10.1016/j.taap.2014.08.002Verma V, Sharma V, Singh V, Sharma S, Bishnoi AK, Chandra V, Maikhuri JP, Dwivedi A, Kumar A, Gupta G. Designed modulation of sex steroid signaling inhibits telomerase activity and proliferation of human prostate cancer cells. Toxicol Appl Pharmacol. 2014 Oct 15; 280 (2): 323–34. DOI: 10.1016/j.taap.2014.08.002Heath EI, Heilbrun LK, Li J, Vaishampayan U, Harper F, Pemberton P, Sarkar FH. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3’- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am. J. Transl Res. 2010 Jul 23; 2 (4): 402–11. PMID: 20733950; PMCID: PMC 2923864. https://pubmed.ncbi.nlm.nih.gov/20733950Heath EI, Heilbrun LK, Li J, Vaishampayan U, Harper F, Pemberton P, Sarkar FH. A phase I dose-escalation study of oral BR-DIM (BioResponse 3,3’- Diindolylmethane) in castrate-resistant, non-metastatic prostate cancer. Am. J. Transl Res. 2010 Jul 23; 2 (4): 402–11. PMID: 20733950; PMCID: PMC 2923864. https://pubmed.ncbi.nlm.nih.gov/20733950Hwang C, Sethi S, Heilbrun LK, Gupta NS, Chitale DA, Sakr WA, Menon M, Peabody JO, Smith DW, Sarkar FH, Heath EI. Anti-androgenic activity of absorption-enhanced 3, 3’-diindolylmethane in prostatectomy patients. Am. J. Transl Res. 2016 Jan 15; 8 (1): 166–76. PMID: 27069550; PMCID: PMC 4759426. https://pubmed.ncbi.nlm.nih.gov/27069550Hwang C, Sethi S, Heilbrun LK, Gupta NS, Chitale DA, Sakr WA, Menon M, Peabody JO, Smith DW, Sarkar FH, Heath EI. Anti-androgenic activity of absorption-enhanced 3, 3’-diindolylmethane in prostatectomy patients. Am. J. Transl Res. 2016 Jan 15; 8 (1): 166–76. PMID: 27069550; PMCID: PMC 4759426. https://pubmed.ncbi.nlm.nih.gov/27069550Pilla Reddy V, Jo H, Neuhoff S. Food constituent- and herb-drug interactions in oncology: Influence of quantitative modelling on Drug labelling. Br. J. Clin. Pharmacol. 2021 Oct; 87 (10): 3988–4000. DOI: 10.1111/bcp.14822Pilla Reddy V, Jo H, Neuhoff S. Food constituent- and herb-drug interactions in oncology: Influence of quantitative modelling on Drug labelling. Br. J. Clin. Pharmacol. 2021 Oct; 87 (10): 3988–4000. DOI: 10.1111/bcp.14822Chan WJ, Adiwidjaja J, McLachlan AJ, Boddy AV, Harnett JE. Interactions between natural products and cancer treatments: underlying mechanisms and clinical importance. Cancer Chemother Pharmacol. 2023 Feb; 91 (2): 103–119. DOI: 10.1007/s00280-023-04504-zChan WJ, Adiwidjaja J, McLachlan AJ, Boddy AV, Harnett JE. Interactions between natural products and cancer treatments: underlying mechanisms and clinical importance. Cancer Chemother Pharmacol. 2023 Feb; 91 (2): 103–119. DOI: 10.1007/s00280-023-04504-zHussaarts KGAM, Hurkmans DP, Oomen-de Hoop E, van Harten LJ, Berghuis S, van Alphen RJ, Spierings LEA, van Rossum-Schornagel QC, Vastbinder MB, van Schaik RHN, van Gelder T, Jager A, van Leeuwen RWF, Mathijssen RHJ. Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen. Cancers (Basel). 2019 Mar 22; 11 (3): 403. DOI: 10.3390/cancers11030403Hussaarts KGAM, Hurkmans DP, Oomen-de Hoop E, van Harten LJ, Berghuis S, van Alphen RJ, Spierings LEA, van Rossum-Schornagel QC, Vastbinder MB, van Schaik RHN, van Gelder T, Jager A, van Leeuwen RWF, Mathijssen RHJ. Impact of Curcumin (with or without Piperine) on the Pharmacokinetics of Tamoxifen. Cancers (Basel). 2019 Mar 22; 11 (3): 403. DOI: 10.3390/cancers11030403Parkin DR, Malejka-Giganti D. Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3’-diindolylmethane and its parent compound indole‑3-carbinol. Cancer Detect Prev. 2004; 28 (1): 72–9. DOI: 10.1016/j.cdp.2003.11.006Parkin DR, Malejka-Giganti D. Differences in the hepatic P450-dependent metabolism of estrogen and tamoxifen in response to treatment of rats with 3,3’-diindolylmethane and its parent compound indole‑3-carbinol. Cancer Detect Prev. 2004; 28 (1): 72–9. DOI: 10.1016/j.cdp.2003.11.006Kim HW, Kim J, Kim J, Lee S, Choi BR, Han JS, Lee KW, Lee HJ. 3,3’-Diindolylmethane inhibits lipopolysaccharide-induced microglial hyperactivation and attenuates brain inflammation. Toxicol Sci. 2014 Jan; 137 (1): 158–67. DOI: 10.1093/toxsci/kft240Kim HW, Kim J, Kim J, Lee S, Choi BR, Han JS, Lee KW, Lee HJ. 3,3’-Diindolylmethane inhibits lipopolysaccharide-induced microglial hyperactivation and attenuates brain inflammation. Toxicol Sci. 2014 Jan; 137 (1): 158–67. DOI: 10.1093/toxsci/kft240Du H, Zhang X, Zeng Y, Huang X, Chen H, Wang S, Wu J, Li Q, Zhu W, Li H, Liu T, Yu Q, Wu Y, Jie L. A Novel Phytochemical, DIM, Inhibits Proliferation, Migration, Invasion and TNF α Induced Inflammatory Cytokine Production of Synovial Fibroblasts From Rheumatoid Arthritis Patients by Targeting MAPK and AKT/mTOR Signal Pathway. Front Immunol. 2019 Jul 23; 10: 1620. DOI: 10.3389/fimmu.2019.01620Du H, Zhang X, Zeng Y, Huang X, Chen H, Wang S, Wu J, Li Q, Zhu W, Li H, Liu T, Yu Q, Wu Y, Jie L. A Novel Phytochemical, DIM, Inhibits Proliferation, Migration, Invasion and TNF α Induced Inflammatory Cytokine Production of Synovial Fibroblasts From Rheumatoid Arthritis Patients by Targeting MAPK and AKT/mTOR Signal Pathway. Front Immunol. 2019 Jul 23; 10: 1620. DOI: 10.3389/fimmu.2019.01620Ramakrishna K, Singh N, Krishnamurthy S. Diindolylmethane ameliorates platelet aggregation and thrombosis: In silico, in vitro, and in vivo studies. Eur J Pharmacol. 2022 Mar 15; 919: 174812. DOI: 10.1016/j.ejphar.2022.174812Ramakrishna K, Singh N, Krishnamurthy S. Diindolylmethane ameliorates platelet aggregation and thrombosis: In silico, in vitro, and in vivo studies. Eur J Pharmacol. 2022 Mar 15; 919: 174812. DOI: 10.1016/j.ejphar.2022.174812Yang H, Seo SG, Shin SH, Min S, Kang MJ, Yoo R, Kwon JY, Yue S, Kim KH, Cheng JX, Kim JR, Park JS, Kim JH, Park JHY, Lee HJ, Lee KW. 3,3’-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity. Mol Nutr Food Res. 2017 Oct; 61 (10). DOI: 10.1002/mnfr.201700119Yang H, Seo SG, Shin SH, Min S, Kang MJ, Yoo R, Kwon JY, Yue S, Kim KH, Cheng JX, Kim JR, Park JS, Kim JH, Park JHY, Lee HJ, Lee KW. 3,3’-Diindolylmethane suppresses high-fat diet-induced obesity through inhibiting adipogenesis of pre-adipocytes by targeting USP2 activity. Mol Nutr Food Res. 2017 Oct; 61 (10). DOI: 10.1002/mnfr.201700119Poornima J, Mirunalini S. Regulation of carbohydrate metabolism by indole‑3-carbinol and its metabolite 3,3’-diindolylmethane in high-fat diet-induced C 57BL/6J mice. Mol Cell Biochem. 2014 Jan; 385 (1–2): 7–15. DOI: 10.1007/s11010‑013‑1808‑2Poornima J, Mirunalini S. Regulation of carbohydrate metabolism by indole‑3-carbinol and its metabolite 3,3’-diindolylmethane in high-fat diet-induced C 57BL/6J mice. Mol Cell Biochem. 2014 Jan; 385 (1–2): 7–15. DOI: 10.1007/s11010‑013‑1808‑2Choi KM, Yoo HS. Amelioration of Hyperglycemia-Induced Nephropathy by 3,3’-Diindolylmethane in Diabetic Mice. Molecules. 2019 Dec 6; 24 (24): 4474. DOI: 10.3390/molecules24244474Choi KM, Yoo HS. Amelioration of Hyperglycemia-Induced Nephropathy by 3,3’-Diindolylmethane in Diabetic Mice. Molecules. 2019 Dec 6; 24 (24): 4474. DOI: 10.3390/molecules24244474

The authors declare that there are no conflicts of interest present.