Induction of apopotosis by methanol extracts of Ficus carica L. in FaDu human hypopharynx squamous carcinoma cells
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Ficus carica L. (fig ) is one of the first cultivated crops and is as old as humans. This plant has been extensively usedas a traditional medicine for treating diseases, such as cough, indigestion, nutritional anemia, and tuberculosis. However, the physiological activity of fig leaves on oral cancer is as yet unknown. In this study, we investigatedthe anticancer effect of methanol extracts of Ficus carica (MeFC) and the mechanism of cell death in human FaDuhypopharyngeal squamous carcinoma cells. MeFC decreased the viability of oral cancer (FaDu) cells but did notaffect the viability of normal (L929) cells, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay and Live and Dead assay. In addition, MeFC induced apoptosis through the proteolytic cleavageof procaspase-3, -9, poly (ADP-ribose) polymerase (PARP), downregulation of Bcl-2, and upregulation of Bax,as determined by 4′,6-diamidino-2-phenylindole dihydrochloride staining and western blot analysis. Moreover, aconcentration of MeFC without cytotoxicity (0.25 mg/mL) significantly suppressed colony formation, a hallmark ofcancer development, and completely inhibited the colony formation at 1 mg/mL. Collectively, these results suggestthat MeFC exhibits a potent anticancer effect by suppressing the growth of oral cancer cells and colony formation viacaspase- and mitochondrial-dependent apoptotic pathways in FaDu human hypopharyngeal squamous carcinomacells. Therefore, the methanol extract of Ficus carcica leaves provide a natural chemotherapeutic drug for human oralcancer.
Abstract
Ficus carica L. (fig ) is one of the first cultivated crops and is as old as humans. This plant has been extensively usedas a traditional medicine for treating diseases, such as cough, indigestion, nutritional anemia, and tuberculosis. However, the physiological activity of fig leaves on oral cancer is as yet unknown. In this study, we investigatedthe anticancer effect of methanol extracts of Ficus carica (MeFC) and the mechanism of cell death in human FaDuhypopharyngeal squamous carcinoma cells. MeFC decreased the viability of oral cancer (FaDu) cells but did notaffect the viability of normal (L929) cells, as determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide assay and Live and Dead assay. In addition, MeFC induced apoptosis through the proteolytic cleavageof procaspase-3, -9, poly (ADP-ribose) polymerase (PARP), downregulation of Bcl-2, and upregulation of Bax,as determined by 4′,6-diamidino-2-phenylindole dihydrochloride staining and western blot analysis. Moreover, aconcentration of MeFC without cytotoxicity (0.25 mg/mL) significantly suppressed colony formation, a hallmark ofcancer development, and completely inhibited the colony formation at 1 mg/mL. Collectively, these results suggestthat MeFC exhibits a potent anticancer effect by suppressing the growth of oral cancer cells and colony formation viacaspase- and mitochondrial-dependent apoptotic pathways in FaDu human hypopharyngeal squamous carcinomacells. Therefore, the methanol extract of Ficus carcica leaves provide a natural chemotherapeutic drug for human oralcancer.
참고문헌 (24)
- Ephraim Philip Lansky, "Ficus spp. (fig): Ethnobotany and potential as anticancer and anti-inflammatory agents", Journal of Ethnopharmacology, 119(2), pp.195~213 (2008), Elsevier BV[DOI]
- M. E. Kislev, "Early Domesticated Fig in the Jordan Valley", Science, 312(5778), pp.1372~1374 (2006), American Association for the Advancement of Science (AAAS)[DOI]
- Mawa S, "Ficus carica L. (Moraceae): phytochemistry, traditional uses and biological activities", Evid Based Complement Alternat Med, 2013, pp.974256~ (2013)[DOI]
- Werbach M, "Healing with food : 281 nutritional healing plans for 50 common ailments" (1993), Harper Collins
- Duke JA, "Handbook of medicinal herbs" (2002), CRC Press
- Melisa I. Barolo, "Ficus carica L. (Moraceae): An ancient source of food and health", Food Chemistry, 164, pp.119~127 (2014), Elsevier BV[DOI]
- Yu Zhang, "Extracts and components of <em>Ficus carica<", em> leaves suppress survival, cell cycle, and migration of triple-negative breast cancer MDA-MB-231 cells, 2018, pp.11, 4377~4386[DOI]
- Risa Purnamasari, "Anticancer activity of methanol extract of Ficus carica leaves and fruits against proliferation, apoptosis, and necrosis in Huh7it cells", Cancer Informatics, 18, pp.117693511984257~ (2019), SAGE Publications[DOI]
- Tomonori Sasahira, "Update of molecular pathobiology in oral cancer: a review", International Journal of Clinical Oncology, 19(3), pp.431~436 (2014), Springer Science and Business Media LLC[DOI]
- Malay Kumar, "Oral cancer: Etiology and risk factors: A review", Journal of Cancer Research and Therapeutics, 12(2), pp.458~463 (2016), Medknow[DOI]
- Wei Lu, "QKI impairs self-renewal and tumorigenicity of oral cancer cells via repression of SOX2", Cancer Biology & Therapy, 15(9), pp.1174~1184 (2014), Informa UK Limited[DOI]
- Susan Elmore, "Apoptosis: A Review of Programmed Cell Death", Toxicologic Pathology, 35(4), pp.495~516 (2007), SAGE Publications[DOI]
- Ashis Mukherjee, "Advances in Cancer Therapy with Plant Based Natural Products", Current Medicinal Chemistry, 8(12), pp.1467~1486 (2001), Bentham Science Publishers Ltd[DOI]
- K. L. King, "CELL CYCLE REGULATION AND APOPTOSIS", Annual Review of Physiology, 60(1), pp.601~617 (1998), Annual Reviews[DOI]
- Kaufmann SH, "Specific proteolytic cleavage of poly(ADP-ribose)polymerase : an early marker of chemotherapy-induced apoptosis", Cancer Res, 53, pp.3976~3985 (1993)
- Kerr JF, "Apoptosis. Its significance in cancer and cancer therapy", Cancer, 73, pp.2013~2026 (1994)[DOI]
- Lou A Smets, "Programmed cell death (apoptosis) and response to anti-cancer drugs", Anti-Cancer Drugs, 5(1), pp.3~9 (1994), Ovid Technologies (Wolters Kluwer Health)[DOI]
- Soltana H, "Antitumoral activity of Ficus carica L. on colorectal cancer cell lines", Cell Mol Biol(Noisy-le-grand), 65, pp.6~11 (2019)
- Arshia Ghanbari, "Biological activities of Ficus carica latex for potential therapeutics in Human Papillomavirus (HPV) related cervical cancers", Scientific Reports, 9(1), pp.1013~ (2019), Springer Science and Business Media LLC[DOI]
- Matthew Links, "Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy", Drugs, 57(3), pp.293~308 (1999), Springer Science and Business Media LLC[DOI]
- Meng-ping Liu, "Sanguisorba officinalis L synergistically enhanced 5-fluorouracil cytotoxicity in colorectal cancer cells by promoting a reactive oxygen species-mediated, mitochondria-caspase-dependent apoptotic pathway", Scientific Reports, 6(1), pp.34245~ (2016), Springer Science and Business Media LLC[DOI]
- Mozafar Khazaei, "Antiproliferative effect of Trifolium pratens L. extract in human breast cancer cells", Nutrition and Cancer, 71(1), pp.128~140 (2019), Informa UK Limited[DOI]
- Khazaei M, "Evaluation of hydro-alcoholic extract of Trifolium pratens L. for its anti-cancer potential on U87MG cell line", Cell J, 20, pp.412~421 (2018)[DOI]
- Monika Raisova, "The Bax", Bcl-2 Ratio Determines the Susceptibility of Human Melanoma Cells to CD95, Journal of Investigative Dermatology, pp.2001, 117(2)[DOI]