Индолкарбинол (Индинол Форто) и доброкачественные заболевания молочных желез в аспекте профилактики онкологических процессов

1. Chen C., Wang Z., Liao Z., Zhang Y., Lei W., Shui X. Aryl hydrocarbon receptor: An emerging player in breast cancer pathogenesis and its potential as a drug target (Review). Mol. Med. Rep. 2024; 29(1): 11. https://dx.doi.org/10.3892/mmr.2023.13134
2. Du H., Zhang X., Zeng Y., Huang X., Chen H., Wang S. et al. 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; 10: 1620. https://dx.doi.org/10.3389/fimmu.2019.01620
3. Banerjee S., Kong D., Wang Z.., Bao B, Hillman G.G., Sarkar F.H. Attenuation of multi-targeted proliferation-linked signaling by 3,3'-diindolylmethane (DIM): from bench to clinic. Mutat. Res. 2011; 728(1-2): 47-66. https://dx.doi.org/10.1016/j.mrrev.2011.06.001
4. Wang M.L., Shih C.K., Chang H.P., Chen Y.H. Antiangiogenic activity of indole-3-carbinol in endothelial cells stimulated with activated macrophages. Food Chem. 2012; 134(2): 811-20. https://dx.doi.org/10.1016/j.foodchem.2012.02.185
5. Chang X., Firestone G.L., Bjeldanes L.F. Inhibition of growth factor-induced Ras signaling in vascular endothelial cells and angiogenesis by 3,3'-diindolylmethane. Carcinogenesis. 2006; 27(3): 541-50. https://dx.doi.org/10.1093/carcin/bgi230
6. Chen D.Z., Qi M., Auborn K.J., Carter T.H. Indole-3-carbinol and diindolylmethane induce apoptosis of human cervical cancer cells and in murine HPV16-transgenic preneoplastic cervical epithelium. J. Nutr. 2001; 131(12): 3294-302. https://dx.doi.org/10.1093/jn/131.12.3294
7. Vezina C.M, Lin T.M., Peterson R.E. AHR signaling in prostate growth, morphogenesis, and disease. Biochem. Pharmacol. 2009; 77(4): 566-76. https://dx.doi.org/10.1016/j.bcp.2008.09.039
8. Safe S., Lee S.O., Jin U.H. Role of the aryl hydrocarbon receptor in carcinogenesis and potential as a drug target. Toxicol. Sci. 2013; 135(1):1-16. https://dx.doi.org/10.1093/toxsci/kft128
9. Qi M., Anderson A.E., Chen D.Z., Sun S., Auborn K.J. Indole-3-carbinol prevents PTEN loss in cervical cancer in vivo. Mol. Med. 2005; 11(1-12): 59-63. https://dx.doi.org/10.2119/2006-00007.Auborn
10. Tamura M., Gu J., Matsumoto K., Aota S., Parsons R., Yamada K.M. Inhibition of cell migration, spreading, and focal adhesions by tumor suppressor PTEN. Science. 1998; 280(5369): 1614-7. https://dx.doi.org/10.1126/science.280.5369.1614
11. Ho J.N., Jun W., Choue R., Lee J. I3C and ICZ inhibit migration by suppressing the EMT process and FAK expression in breast cancer cells. Mol. Med. Rep. 2013; 7(2): 384-8. https://dx.doi.org/10.3892/mmr.2012.1198
12. Pani S., Sahoo A., Patra A., Debata P.R. Phytocompounds curcumin, quercetin, indole-3-carbinol, and resveratrol modulate lactate-pyruvate level along with cytotoxic activity in HeLa cervical cancer cells. Biotechnol. Appl. Biochem. 2021; 68(6): 1396-402. https://dx.doi.org/10.1002/bab.2061
13. Lopez-Vazquez A., Garcia-Banuelos J.J., Gonzalez-Garibay A.S., Urzua-Lozano P.E., Del Toro-Arreola S., Bueno-Topete M.R. et al. IRS-1 pY612 and Akt-1/PKB pT308 phosphorylation and antiinflammatory effect of diindolylmethane in adipocytes cocultured with macrophages. Med. Chem. 2017; 13(8): 727-33. https://dx.doi.org/10.2174/1573406413666170922095011
14. Chichai A.S., Popova T.N., Kryl'skii E.D., Oleinik S.A., Razuvaev G.A. Indole-3-carbinol mitigates oxidative stress and inhibits inflammation in rat cerebral ischemia/reperfusion model. Biochimie. 2023; 213: 1-11. https://dx.doi.org/10.1016/j.biochi.2023.04.018
15. Srikanth Y., Julius T., Gayathri M., Tuyishime H.S., Gelege M.D., Kumar S.S. et al. Indole 3 carbinol attenuated memory impairment, oxidative stress, inflammation, and apoptosis in bilateral common carotid artery occlusion induced brain damage in rats. 3Biotech. 2025; 15(2): 51. https://dx.doi.org/10.1007/s13205-024-04199-w
16. Madison C.A., Hillbrick L., Kuempel J., Albrecht G.L., Landrock K.K., Safe S. et al. Intestinal epithelium aryl hydrocarbon receptor is involved in stress sensitivity and maintaining depressive symptoms. Behav. Brain Res. 2023; 440: 114256. https://dx.doi.org/10.1016/j.bbr.2022.114256
17. Qazi A., Comiskey S., Calzadilla N., Amin F., Sharma A., Khin E. et al. Potential dietary and therapeutic strategies involving indole-3-carbinole in preclinical models of intestinal inflammation. Nutrients. 2023; 15(23): 4980. https://dx.doi.org/10.3390/nu15234980
18. Ramakrishna K., Sinku S., Majumdar S., Singh N., Gajendra T.A., Rani A. et al. Indole-3-carbinol ameliorated the thioacetamide-induced hepatic encephalopathy in rats. Toxicology. 2023; 492: 153542. https://dx.doi.org/10.1016/j.tox.2023.153542
19. Holloman B.L., Wilson K., Cannon A., Nagarkatti M., Nagarkatti P.S. Indole-3-carbinol attenuates lipopolysaccharide-induced acute respiratory distress syndrome through activation of AhR: role of CCR2+ monocyte activation and recruitment in the regulation of CXCR2+ neutrophils in the lungs. Front. Immunol. 2024; 15: 1330373. https://dx.doi.org/10.3389/fimmu.2024.1330373
20. Baez-Gonzalez A.S., Carrazco-Carrillo J.A., Figueroa-Gonzalez G., Quintas-Granados L.I., Padilla-Benavides T., Reyes-Hernandez O.D. Functional effect of indole-3 carbinol in the viability and invasive properties of cultured cancer cells. Biochem. Biophys. Rep. 2023; 35: 101492. https://dx.doi.org/10.1016/j.bbrep.2023.101492
21. Paltsev M., Kiselev V., Drukh V., Muyzhnek E., Kuznetsov I., Andrianova E. et al. First results of the double-blind randomized placebo-controlled multicenter clinical trial of DIM-based therapy designed as personalized approach to reverse prostatic intraepithelial neoplasia (PIN). EPMA J. 2016; 7(1): 5. https://dx.doi.org/10.1186/s13167-016-0057-3
22. Thomson C.A., Chow H.H.S., Wertheim B.C., Roe D.J., Stopeck A., Maskarinec G. et al. A randomized, placebo-controlled trial of diindolylmethane for breast cancer biomarker modulation in patients taking tamoxifen. Breast Cancer Res. Treat. 2017; 165(1): 97-107. https://dx.doi.org/10.1007/s10549-017-4292-7
23. National Toxicology Program. Toxicology studies of indole-3-carbinol in F344/N rats and B6C3F1/N mice and toxicology and carcinogenesis studies of indole-3-carbinol in Harlan Sprague Dawley rats and B6C3F1/N mice (gavage studies). Natl. Toxicol. Program Tech. Rep. Ser. 2017; (584): NTP-TR-584. https://dx.doi.org/10.22427/NTP-TR-584
24. Reyes-Hernández O.D., Figueroa-González G., Quintas-Granados L.I., Gutiérrez-Ruíz S.C., Hernández-Parra H., Romero-Montero A. et al. 3,3'-Diindolylmethane and indole-3-carbinol: potential therapeutic molecules for cancer chemoprevention and treatment via regulating cellular signaling pathways. Cancer Cell Int. 2023; 23(1): 180. https://dx.doi.org/10.1186/s12935-023-03031-4
25. Dalessandri K.M., Firestone G.L., Fitch M.D., Bradlow H.L., Bjeldanes L.F. 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. https://dx.doi.org/10.1207/s15327914nc5002_5
26. Киселев В.И., Сметник В.П., Сутурина Л.В., Селиванов С.П., Рудакова Е.Б., Рахматуллина И.Р., Андреева Е.Н., Фадеева Н.И., Хасанов Р.Ш., Кулагина Н.В., Рожкова Н.И., Артымук Н.В., Гависова А.А., Муйжнек Е.Л., Кузнецов И.Н., Друх В.М. Индолкарбинол (Индинол Форто) – метод мультитаргетной терапии при циклической мастодинии. Акушерство и гинекология. 2013; 7: 56-62.
27. Родионов В.В., Сметник А.А., Сенча А.Н., Кометова В.В., Бикеев Ю.В., Ашрафян Л.А. Алгоритм диагностики и лечения доброкачественной дисплазии молочной железы. Акушерство и гинекология. 2022; 6(Приложение): 23-34.
28. Общая характеристика лекарственного препарата Индинол Форто. ЛП-N=(007558)-(РГ-RU) от 05.11.2024.

Поступила 19.06.2025

Принята в печать 25.06.2025