Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press137710.17650/1994-4098-2025-21-2-75-83MAMMOLOGY. REVIEWSМАММОЛОГИЯ. ОБЗОРНЫЕ СТАТЬИModern concepts of basic therapy for diffuse dyshormonal dysplasia of the mammary glandsСовременные представления о базовой терапии диффузной дисгормональной дисплазии молочных железVуsotskayaI. V.ВысоцкаяИ. В.
Russian Federation

Build. 2, 8 Trubetskaya St., Moscow 119991

119991 Москва, ул. Трубецкая, 8, стр. 2

https://orcid.org/0000-0003-4893-8770KimE. A.КимЕ. А.
Russian Federation

Build. 2, 8 Trubetskaya St., Moscow 119991

24 Kashirskoe Shosse, Moscow 115522

Елена Анатольевна Ким

119991 Москва, ул. Трубецкая, 8, стр. 2

115522 Москва, Каширское шоссе, 24

helene-kim@yandex.ruKushnirM. A.КушнирМ. А.
Russian Federation

Build. 2, 8 Trubetskaya St., Moscow 119991

119991 Москва, ул. Трубецкая, 8, стр. 2

I.M. Sechenov First Moscow State Medical University (Sechenov University), Ministry of Health of RussiaФГАОУ ВО Первый Московский государственный медицинский университет им. И. М. Сеченова (Сеченовский Университет) Минздрава РоссииN.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н. Н. Блохина» Минздрава России0308202521275830208202502082025https://ojrs.abvpress.ru/ojrs/article/view/1377

The presented work is devoted to modern concepts of basic therapy of dyshormonal dysplasia – the most common diffuse disease of the mammary glands. In Russia, one of the most popular medications for the specific correction of mastalgia–mastodynia associated with this disease is Mastodinon. The active component of the drug – the extract of Vitex agnus-castus (chaste tree, monk’s pepper) contains the flavonoid casticin, which determines the therapeutic potential of this plant. The authors present the latest data from the world literature on the clinical and biological effects of сasticin as well as its molecular effects on the processes of epigenetic rearrangements in benign breast dysplasia. Also the potential role of casticin in the prevention of cancer was assessed.

Работа посвящена современным представлениям о базовой терапии дисгормональной дисплазии – самого частого диффузного заболевания молочных желез. В России одним из наиболее востребованных лекарственных препаратов для специфической коррекции симптомов масталгии–мастодинии при данном заболевании является Мастодинон. Активный компонент препарата – экстракт Витекса священного (Vitex agnus-castus) – содержит флавоноид кастицин, обусловливающий терапевтический потенциал этого растения. Авторами приведены последние данные мировой литературы, касающиеся клинических и биологических эффектов кастицина, а также его молекулярных эффектов на процессы эпигенетических перестроек при доброкачественной дисплазии молочных желез. Оценена потенциальная роль кастицина в профилактике онкологических заболеваний.

benign breast dysplasiamammary glandmastalgiamastodyniaepigenetic rearrangementmolecular mechanismchemoprophylaxiscasticinbreast cancerдисгормональная дисплазиямолочная железамасталгиямастодинияэпигенетическая перестройкамолекулярный механизмхимиопрофилактикакастицинрак молочной железыZubkin V.I. Pathogenesis, diagnostics, complex treatment and prevention of relapses of benign dysplasia of the mammary glands. Author’s abstract of thesis ... of doctor of medicine. Moscow, 2004. 209 p. (In Russ.).Зубкин В.И. Патогенез, диагностика, комплексное лечение и профилактика рецидивов доброкачественных дисплазий молочных желез. Автореф. дис. … д-ра мед. наук. М., 2004. 209 с.Radzinskiy V.E., Ordiyants I.M. Premenstrual syndrome and benign dysplasia of the mammary glands – realities and prospects. Sovremennaya meditsinskaya nauka = Modern Medical Science 2011;(1):5–19. (In Russ.).Радзинский В.Е., Ордиянц И.М. Предменструальный синдром и доброкачественные дисплазии молочных желез – реалии и перспективы. Современная медицинская наука 2011;(1):5–19.Ovsyannikova T.V. Benign hyperplasia of the mammary glands: antiproliferative therapy. Russkiy meditsinskiy zhurnal. Mat i ditya = Russian Medical Journal. Mother and Child 2018;1(1):67–70. (In Russ.). DOI: 10.32364/2618-8430-2018-1-1-67-70Овсянникова Т.В. Доброкачественные гиперплазии молочных желез: антипролиферативная терапия. Русский медицинский журнал. Мать и дитя 2018;1(1):67–70. DOI: 10.32364/2618-8430-2018-1-1-67-70Burdina L.M. Benign hyperplasia of mammary glands, development features, differential diagnostics. Radiologiya – praktika = Radiology – Practice 2007;(3):44–8. (In Russ.).Бурдина Л.М. Доброкачественные гиперплазии молочных желез, особенности развития, дифференциальная диагностика. Радиология – практика 2007;(3):44–8.Zeigler R.G., Faupel-Badger J.M., Sue I.Y. et al. A new approach to measuring estrogen exposure and metabolism in epidemiologic studies. J Steroid Biochem Mol Biol 2010;121(3–5):538–45. DOI: 10.1016/j.jsbmb.2010.03.068Webster D.E., He Y., Chen S.N. et al. Opioidergic mechanisms underlying the actions of Vitex agnus-castus L. Biochem Pharmacol 2011;81(1):170–7.Suturina L.V., Popova L.N. Dynamics of clinical symptoms and correction of antioxidant deficiency in patients with dyshormonal dysplasia of the mammary glands using the drug “Mastodynon”. Akusherstvo i ginekologiya = Obstetrics and Gynecology 2012;8(1):1–4. (In Russ.).Сутурина Л.В., Попова Л.Н. Динамика клинических симптомов и коррекция антиоксидантной недостаточности у больных дисгормональной дисплазией молочных желез препаратом «Мастодинон». Акушерство и гинекология 2012;8(1):1–4.Radzinskiy V.E., Ordiyants I.M. Mammary glands and gynecological diseases: from common pathogenetic views to practical solutions. Zdorovye zhenshchiny = Women’s Health 2013;6(113):104–9. (In Russ.).Радзинский В.Е., Ордиянц И.М. Молочные железы и гинекологические болезни: от общности патогенетических воззрений к практическим решениям. Здоровье женщины 2013;6(113):104–9.Sotnikova L.S., Sotnikov A.A., Udut E.V. Diagnostics of diffuse dyshormonal dysplasia of the mammary glands. Ginekologiya. Endokrinologiya = Gynecology. Endocrinology 2015;1(102):17–20. (In Russ.).Сотникова Л.С., Сотников А.А., Удут Е.В. Диагностика диффузной дисгормональной дисплазии молочных желез. Гинекология. Эндокринология 2015;1(102):17–20.Galati G., Teng S., Moridani M. et al. Cancer chemoprevention and apoptosis mechanisms induced by dietary polyphenolics. Drug Metabol Drug Interact 2000;17(1–4):311–49. DOI: 10.1515/dmdi.2000.17.1-4.311Vysotskaya I.V., Letyagin V.P. Pharmacological effects and molecular mechanisms of action of a herbal medicine based on Vitex agnus-castus. Opukholi zhenskoy reproduktivnoy sistemy = Tumors of Female Reproductive System 2017;13(1):14–9. (In Russ.). DOI: 10.17650/1994-4098-2017-13-1-14-19Высоцкая И.В., Летягин В.П. Фармакологические эффекты и молекулярные механизмы действия лечебного фитопрепарата на основе Vitex agnus-castus. Опухоли женской репродуктивной системы 2017;13(1):14–9. DOI: 10.17650/1994-4098-2017-13-1-14-19Radzinskiy V.E., Ordiyants I.M., Maslennikova M.N. et al. Possibilities of therapy for the combination of uterine fibroids and benign breast dysplasia. Akusherstvo i ginekologiya = Obstetrics and Gynecology 2013;(4). (In Russ.).Радзинский В.Е., Ордиянц И.М., Масленникова М.Н. и др. Возможности терапии сочетания миомы матки и доброкачественной дисплазии молочных желез. Акушерство и гинекология 2013;(4).Mirmolaei S., Olfatbakhsh A., Fallahhosseini H. et al. The effect of Vitagnus on cyclic breast pain in women of reproductive age. Journal of Babol University of Medical Sciences 2016;18(9):7–13.Niazi A., Baradaran Rahimi V., Hatami H. et al. Effective medicinal plants in the treatment of the cyclic mastalgia (breast pain): A review. J Pharmacopuncture 2019;22(3):131–9. DOI: 10.3831/KPI.2019.22.017Osouli Tabrizi Sh., Meedya Sh., Ghassab-Abdollahia N. et al. The effect of the herbal medicine on severity of cyclic mastalgia: A systematic review and meta-analysis. J Complement Integr Med 2021;19(4):855–68. DOI: 10.1515/jcim-2020-0531Sasaki K., Miki Y., Hirakawa H. et al. Immunolocalisation or estrogen-producing and metabolizing enzymes in bening breast disease: Comparison with normal breast and breast сarcinoma. Cancer Sci 2010;101(10):2286–92. DOI: 10.1111/j.1349-7006.2010.01673.xSasaki K., Miki Y., Hirakawa H. et al. Immunolocalisation or estrogen-producing and metabolizing enzymes in bening breast disease: Comparison with normal breast and breast сarcinoma. Cancer Sci 2010;101(10):2286–92. DOI: 10.1111/j.1349-7006.2010.01673.xKogan I.Yu. Mastopathy: new approaches to diagnostics and pathogenetic therapy. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women’s Diseases 2010. (In Russ.).Коган И.Ю. Мастопатия: новые подходы к диагностике и патогенетической терапии. Журнал акушерства и женских болезней 2010. Kogan I.Yu. Mastopathy: new approaches to diagnostics and pathogenetic therapy. Zhurnal akusherstva i zhenskikh bolezney = Journal of Obstetrics and Women’s Diseases 2010. (In Russ.).Fleischer T., Frigessi A., Johnson K.С. et al. Genome-wide DNA methylation profiles in progression to in situ and invasive carcinoma of the breast with impact on gene transcription and prognosis. Genome Biol 2014;15(8):435.Fleischer T., Klajic J., Aure M.R. et al. DNA methylation signature (SAM40) identifies subgroups of the luminal A breast cancer samples with distinct survival. Oncotarget 2017;8(1):1074–82.Fleischer T., Klajic J., Aure M.R. et al. DNA methylation signature (SAM40) identifies subgroups of the luminal A breast cancer samples with distinct survival. Oncotarget 2017;8(1):1074–82.Rothstein M.A., Cai Y., Marchant G. Ethical implications of epigenetics research. Nat Rev Genet 2009;10(4):224. DOI: 10.1038/nrg2562Ma L., Zhang M., Zhao R. et al. Plant natural products: Promising resources for cancer chemoprevention. Molecules 2021;26(4):933. DOI: 10.3390/molecules260409Rasul A., Zhao B.J., Liu J. et al. Molecular mechanisms of action of casticin: Updated information on its antitumor functions. Asian Pac J Cancer Prev 2014;15:9049–58. DOI:1 0.7314/APJCP.2014.15.21.9049Husna N., Van Ahmad V.A.N., Layli N. et al. Coastal medicinal plant Vitex rotundifolia: A mini-review of its bioactive compounds and pharmacological activity. Trad Med Res 2021;6:11. DOI: 10.53388/TMR20201128209Kamal N., Mio Asni N.S., Rozlan I.N.A. Traditional medical uses, phytochemistry, biological properties and plant health applications Vitex sp. Plants (Basel) 2022;11(15):1944. DOI: 10.3390/plants11151944Zhou Y., Tian L., Long L. et al. Casticin potentiates TRAIL induced apoptosis of gastric cancer cells through endoplasmic reticulum stress. PLoS One 2013;8(3):e58855. DOI: 10.1371/journal.pone.0058855Zhou Y., Peng Y., Mao Q.Q. et al. Casticin induces caspase mediated apoptosis via activation of mitochondrial pathway and upregulation of DR5 in human lung cancer cells. Asian Pac J Trop Med 2013;6(5):372–8. DOI: 10.1016/S1995-7645(13)60041-3Kikuchi H., Yuan B., Nishimura Y. et al. Cytotoxicity of Vitex agnus-castus fruit extract and its main component, casticin, correlates with differentiation status in leukemia. Int J Oncol 2013;43(6):1976–84. DOI: 10.3892/ijo.2013.2133Chan E.W.C., Wong S.K., Chan H.T. Casticin from Vitex species: A brief overview of its antitumor and anti-inflammatory properties. J Integr Med 2018;16(3):147–52. DOI: 10.1016/j.joim.2018.03.001Ramchandani S., Naz I., Lee J.H. et al. An overview of the potential antitumor effects of casticin. Molecules 2020;25(6):1287. DOI: 10.3390/molecules25061287Li S., Wang L., Cao S. et al. Casticin inhibits hepatocellular carcinoma stem cells by disrupting reciprocal negative regulation between DNMT1 and miR-148a-3p. Toxicol Appl Pharmacol 2020;396:114998. DOI: 10.1016/j.taap.2020.114998Wang S., Umrath F., Cen W. et al. Pre-conditioning with IFN- and hypoxia enhances the angiogenic potential of iPSC-derived MSC secretome. Cells 2022;11:988. DOI: 10.3390/cells11060988Da Silva Costa P.M., Leyenne Alves Sales S., Pascoalino Pinheiro D. et al. Epigenetic reprogramming in cancer: From diagnosis to treatment. Front Cellular Dev Biol 2023;11:1116805. DOI: 10.3389/fcell.2023.1116805Yang J., Song Y.C., Dang C.X. et al. Serum peptidoma profiling in patients with gastric cancer. Clean Exp Med 2012;12:79–87. DOI: 10.1007/s10238-011-0149-2Forney C., Rossi M., Borromeo I. et al. Flavonoids: Myth or reality for cancer therapy? Molecules 2021;26(12):3583. DOI: 10.3390/molecules26123583Chan E.W.C., Kuin Wong S., Tuck Chan H. Casticin from Vitex species: A short review on its anticancer and anti-inflammatory properties. J Integr Med 2018;16(3):147–52. DOI: 10.1016/j.joim.2018.03.001Moloney J.N., Kotter T.G. ROS signaling in cancer biology. Semin Cell Dev Biol 2018;80:50–64.Galan-Moya E.M., Alcaraz-Sanabria A., Nieto-Jimenez C. et al. Pharmacological screening reveals synthetic lethality interactions with Chk1 inhibitors in basal-like breast and ovarian cancer. Cancer Res 2018;78(13 Suppl):1608. DOI: 10.1158/1538-7445.AM2018-1608Fu C., Zhang K., Wang M., Qiu F. Casticin and chrysosplenol D from Artemisia annua L. induce apoptosis by inhibiting topoisomerase IIα in human non-small-cell lung cancer cells. Phytomedicine 2022;100:154095. DOI: 10.1016/j.phymed.2022.154095Cao X., Hu X., Xu X. et al. Casticin suppresses the stem system associated with self-renewal through miR-342-3p-mediated suppression of FoxM1 in cervical cancer cells. Phytomedicine 2024;135:56036. DOI: 10.1016/j.phymed.2024.156036Wu T., Xiang M., Li Y. et al. Exploration of the pharmacological mechanism of vitexicarpin against triple-negative breast cancer in network pharmacology. Front Biosci (Landmark Ed) 2023;28(12):341. DOI: 10.31083/j.fbl2812341Wu T., Xiang M., Li Y. et al. Exploration of the pharmacological mechanism of vitexicarpin against triple-negative breast cancer in network pharmacology. Front Biosci (Landmark Ed) 2023;28(12):341. DOI: 10.31083/j.fbl2812341