Valeriana Officinalis L. Kök Ekstraktları Meme Kanseri Hücre Hattı MCF-7'de Programlanmış Hücre Ölümü Yolaklarını Kontrol Edebilir

Yıl 2023, Cilt: 10 Sayı: 4, 289 - 295, 28.12.2023

Delfin Alpsoy , Berrin Tuğrul , Zübeyde Öztel , Erdal Balcan

https://doi.org/10.34087/cbusbed.1257111

Öz

Günümüzde doğal ürünlerden elde edilen fitokimyasallar kanserin tedavisi ve önlenmesi için yeni stratejiler geliştirmede umut verici ajanlar olarak kabul edilmektedir. Sirkadiyen ritme bağlı uyku bozukluklarını ve uykusuzluğu tedavi etmek için yaygın olarak kullanılan bir takviye olan kediotu (Valeriana officinalis L.) kök ekstreleri bu bağlamda iyi bir aday olabilir. Bu çalışmada, kediotu kökü ekstraktının bir insan meme kanseri modeli olan MCF-7 hücrelerinde programlanmış hücre ölüm mekanizmalarını indükleyip indüklemediği hipotezini ortaya koyduk. Hipotezi test etmek için MCF-7 hücrelerini 24 saat boyunca farklı konsantrasyonlarda ekstrakt ile muamele ettik. Apoptotik morfolojiyi ve apoptotik indeksi değerlendirmek için Giemsa boyamasını, otofajik akı ile ilişkili vakuolleri belirlemek için ise monodansilkadaverin testini kullandık. Bulgularımız, kediotu köklerinden elde edilen ekstraktların insan meme kanseri hücresi MCF-7 üzerinde doza bağlı bir şekilde apototik ve otofajik etkiye sahip olduğunu göstermiştir. Ayrıca, hücrelerin tipik parke taşı morfolojisi ekstrakt uygulamalarından sonra bozulmuş ve hücreler birbirleriyle temasını kaybetmiştir. Bu morfolojik değişiklik, ekstrasellüler matriks veya komşu hücrelerle hücre iletişiminin kaybı ile indüklenen programlanmış bir hücre ölümü tipi olan anoikise atfedilmiştir. Sonuç olarak, bu çalışmada birçok metodolojik eksiklik olmasına rağmen, bulgularımız Valeriana officinalis L.'nin meme kanseri tedavisinde potansiyel bir anti-kanser ajan olabileceğini düşündürmektedir.

Anahtar Kelimeler

Fitoterapi, Valeriana officinalis L.., Meme kanseri, Apoptosis, Otofaji, Anoikis

Destekleyen Kurum

Manisa Celal Bayar Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi

Proje Numarası

2021-121

Teşekkür

Bu çalışma Manisa Celal Bayar Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi tarafından 2021/121 proje numarası ile desteklenmiştir. Bilimsel Araştırma Koordinasyon Birimi’ne desteklerinden dolayı teşekkür ederiz.

The Root Extracts of Valeriana Officinalis L. may Control Programmed Cell Death Pathways in Breast Cancer Cell Line, MCF-7

Öz

Natural product-derived phytochemicals are now accepted as promising agents in developing new strategies for cancer treatment and prevention. The root extracts of valerian (Valeriana officinalis L.), which is a supplement widely used for improving circadian rhythm-dependent sleep disorders and insomnia, might be a good candidate in that context. In the present study we hypothesized whether extract of valerian root induce programmed cell death machineries in a human breast cancer model, MCF-7 cells. To test the hypothesis, we treated MCF-7 cells with the extract at different concentrations for 24 h. Giemsa staining was used to evaluate the apoptotic morphology and apoptotic index, and monodancylcadaverine assay was used to determine vacuoles that are associated with autophagic flux. Our results indicated that extracts of the roots of valerian have apototic and autophagic effect on human breast cancer cell MCF-7 in a dose dependent manner. Moreover, the typical cobblestone morphology of the cells was disrupted after the extract treatments and the cells lost contact with each other. This morphological alteration was attributed to anoikis, is a programmed cell death type induced by loss of cell communication with extracellular matrix or neighboring cells. In conclusion, although this study has many methodological shortcomings, our findings suggest that Valeriana officinalis L. might be a potential anti-cancer agent for the treatment of breast cancer.

Anahtar Kelimeler

Phytotherapy, Valeriana officinalis L., Breast cancer, Apoptosis, Autophagy, Anoikis

Proje Numarası

2021-121

Kaynakça

• 1. Harbeck, N, Gnant, M, Breast cancer. Lancet, 2017, 389, 1134-1150.
• 2. Akram, M, Iqbal, M, Daniyal, M, Khan, A,U, Awareness and current knowledge of breast cancer. Biological Research, 2017, 50, 33.
• 3. Chairez-Ramirez, M.H, Moreno-Jimenez, M.R, Gonzalez-Laredo, R.F, Gallegos-Infante, J.A, Rocha-Guzman, N.E, Lupane-type triterpenes and their anti-cancer activities against most common malignant tumors: a review. EXCLI Journal, 2016, 15, 758-771.
• 4. Hsu, R.J, Hsu, Y.C, Chen, S.P, Fu, C.L, Yu, J.C, Chang, F.W, Chen, Y.H, Liu, J.M, Ho, J.Y, Yu, C.P, The triterpenoids of Hibiscus syriacus induce apoptosis and inhibit cell migration in breast cancer cells. BMC Complementary and Alternative Medicine, 2015, 15, 65.
• 5. Ali-Seyed, M, Jantan, I, Vijayaraghavan, K, Bukhari, S.N, Betulinic acid: recent advances in chemical modifications, effective delivery, and molecular mechanisms of a promising anticancer therapy, Chemical Biology & Drug Design, 2016, 87, 517-536.
• 6. George, B.P, Chandran, R, Abrahamse, H, Role of phytochemicals in cancer chemoprevention: insights. Antioxidants, 2021, 10, 1-23.
• 7. Mohan, S.G, Swetha, M, Keerthana, C.K, Rayginia, T.P, Anto, R.J, Cancer chemoprevention: a strategic approach using phytochemicals. Frontiers in Pharmacology, 2021, 12, 809308.
• 8. Choudhari, A.S, Mandave, P.C, Deshpande, M, Ranjekar, P, Prakash, O, Phytochemicals in cancer treatment: from preclinical studies to clinical practice. Frontiers in Pharmacology, 2019, 10, 1614.
• 9. Ranjan, A, Ramachandran, S, Gupta, N, Kaushik, I, Wright, S, Srivastava, S, Das, H, Srivastava, S, Prasad, S, Srivastava, S.K, Role of phytochemicals in cancer prevention. International Journal of Molecular Sciences, 2019, 20, 1-17.
• 10. Zubair, H, Azim, S, Ahmad, A, Khan, M.A, Patel, G.K, Singh, S, Singh, A.P, Cancer chemoprevention by phytochemicals: nature's healing touch, Molecules, 2017, 22, 1-24.
• 11. Kotecha, R, Takami, A, Espinoza, J.L, Dietary phytochemicals and cancer chemoprevention: a review of the clinical evidence, Oncotarget, 2016, 7, 52517-52529.
• 12. Fernandez, S, Wasowski, C, Paladini, A.C, Marder, M, Sedative and sleep-enhancing properties of linarin, a flavonoid-isolated from Valeriana officinalis, Pharmacology Biochemistry and Behavior, 2004, 77, 399-404.
• 13. Becker, H, Chavadej, S, Valepotriate production of normal and colchicine-treated cell suspension cultures of Valeriana wallichii, Journal of Natural Products, 1985, 48, 17-21.
• 14. Jia, J, Zhang, B, Effect of valerian extract (V3d) on cardiovascular system [J], Journal of Guangxi College of Traditional Chinese Medicine, 1999, 16, 40-42.
• 15. Hadley, S, Petry, J.J, Valerian. American Family Physician, 2003, 67, 1755-1758.
• 16. Shi, F, Li, Y, Han, R, Fu, A, Wang, R, Nusbaum, O, Qin, Q, Chen, X, Hou, L, Zhu, Y, Valerian and valeric acid inhibit growth of breast cancer cells possibly by mediating epigenetic modifications. Scientific Reports, 2021, 11, 1-11.
• 17. Biederbick, A, Kern, H.F, Elsasser, H.P, Monodansylcadaverine (MDC) is a specific in vivo marker for autophagic vacuoles, European Journal of Cell Biology, 1995, 66, 3-14.
• 18. Li, W.W, Li, J, Bao, J.K, Microautophagy: lesser-known self-eating. Cellular and Molecular Life Sciences, 2012, 69, 1125-1136.
• 19. Mizushima, N, Noda, T, Yoshimori, T, Tanaka, Y, Ishii, T, George, M.D, Klionsky, D.J, Ohsumi, M, Ohsumi, Y, A protein conjugation system essential for autophagy, Nature, 1998, 395, 395-398.
• 20. Kroemer, G, Marino, G, Levine, B, Autophagy and the integrated stress response, Molecular Cell, 2010, 40, 280-293.
• 21. Yang, Z, Klionsky, D.J, Mammalian autophagy: core molecular machinery and signaling regulation. Current Opinion in Cell Biology, 2010, 22, 124-131.
• 22. Li, X, He, S, Ma, B, Autophagy and autophagy-related proteins in cancer. Molecular Cancer, 2020, 19, 1-16.
• 23. Marino, G, Niso-Santano, M, Baehrecke, E.H, Kroemer, G, Self-consumption: the interplay of autophagy and apoptosis. Nature Reviews Molecular Cell Biology, 2014, 15, 81-94.
• 24. de Araujo Jr, R.F, de Souza, T.P, Pires, J.G, Soares, L.A, de Araujo, A.A, Petrovick, P.R, Macedo, H.D,de Sa Leitao Oliveira, A.L, Guerra, G.C, A dry extract of Phyllanthus niruri protects normal cells and induces apoptosis in human liver carcinoma cells, Experimental Biology and Medicine, 2012, 237, 1281-1288.
• 25. Safarzadeh, E, Sandoghchian Shotorbani, S, Baradaran, B, Herbal medicine as inducers of apoptosis in cancer treatment, Advanced Pharmaceutical Bulletin, 2014, 4(Suppl 1), 421-427.
• 26. Lee, Y, Roles of circadian clocks in cancer pathogenesis and treatment. Experimental & Molecular Medicine, 2021, 53, 1529-1538.
• 27. Sulli, G, Lam, M.T.Y, Panda, S, Interplay between circadian clock and cancer: new frontiers for cancer treatment, Trends in Cancer, 2019, 5, 475-494.
• 28. Taddei, M.L, Giannoni, E, Fiaschi, T, Chiarugi, P, Anoikis: an emerging hallmark in health and diseases, Journal of Pathology, 2012, 226, 380-393.
• 29. Hilmarsdottir B, Briem E, Halldorsson S, Kricker J, Ingthorsson S, Gustafsdottir S, Maelandsmo, G.M, Magnusson, M.K, Gudjonsson, T, Inhibition of PTP1B disrupts cell-cell adhesion and induces anoikis in breast epithelial cells, Cell Death & Disease, 2017, 8, e2769.
• 30. Tan, Y.Z, Peng, C, Hu, C.J, Li, H.X, Li, W.B, He, J.L, Li, Y.Z, Zhang, H, Zhang, R.Q, Wang, L.X, Cao, Z.X, Iridoids from Valeriana jatamansi induce autophagy-associated cell death via the PDK1/Akt/mTOR pathway in HCT116 human colorectal carcinoma cells, Bioorganic Chemistry, 2019, 87, 136-41.
• 31. Yang, B, Zhu, R, Tian, S, Wang, Y, Lou, S, Zhao, H, Jatamanvaltrate P induces cell cycle arrest, apoptosis and autophagy in human breast cancer cells in vitro and in vivo, Biomedicine & Pharmacotherapy, 2017, 89, 1027-1036.
• 32. Şenkul, Ç, Kaya, S, Geographical distribution of endemic plants of Turkey. Türk Coğrafya Dergisi. 2017; 69: 109-120.