Inhibition of cell growth and induction of apoptosis by acacetin in FaDu human pharyngeal carcinoma cells
2
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Acacetin, which is present in damiana (Turnera diffusa ) and black locust (Robinia pseudoacacia ), has severalpharmacologic activities such as antioxidant, anti-inflammatory, and anti-proliferative effects on cancer cells. However, the effect of acacetin on head and neck cancers has not been clearly established. This study aimedto examine the effects of acacetin on cell growth and apoptosis induction in FaDu human pharyngeal carcinomacells. These were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, Live/Deadcell assay, 4′,6-diamidino-2-phenylindole dihydrochloride staining, caspase-3 and caspase-7 activation assay, andimmunoblotting in FaDu cells. Acacetin induced FaDu cell death in a dose-dependent manner, with an estimatedIC50 value of 41.9 µM, without affecting the viability of L-929 mouse fibroblasts as normal cells. Acacetin treatmentresulted in nuclear condensation in the FaDu cells. It promoted the proteolytic cleavage of procaspase-3, -7, -8, and-9 with increasing amounts of the cleaved caspase isoforms in FaDu cells. Acacetin-induced apoptosis in FaDu cellswas mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting showed downregulation of the anti-apoptotic mitochondrial proteins Bcl-2 and Bcl-xL, but upregulationof the mitochondria-dependent pro-apoptotic proteins Bax and Badin FaDu cells after acacetin treatment. Thesefindings indicate that acacetin inhibits cell proliferation and induces apoptotic cell death in FaDu human pharyngealcarcinoma cells via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediatedintrinsic apoptotic pathway.
Abstract
Acacetin, which is present in damiana (Turnera diffusa ) and black locust (Robinia pseudoacacia ), has severalpharmacologic activities such as antioxidant, anti-inflammatory, and anti-proliferative effects on cancer cells. However, the effect of acacetin on head and neck cancers has not been clearly established. This study aimedto examine the effects of acacetin on cell growth and apoptosis induction in FaDu human pharyngeal carcinomacells. These were investigated by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assay, Live/Deadcell assay, 4′,6-diamidino-2-phenylindole dihydrochloride staining, caspase-3 and caspase-7 activation assay, andimmunoblotting in FaDu cells. Acacetin induced FaDu cell death in a dose-dependent manner, with an estimatedIC50 value of 41.9 µM, without affecting the viability of L-929 mouse fibroblasts as normal cells. Acacetin treatmentresulted in nuclear condensation in the FaDu cells. It promoted the proteolytic cleavage of procaspase-3, -7, -8, and-9 with increasing amounts of the cleaved caspase isoforms in FaDu cells. Acacetin-induced apoptosis in FaDu cellswas mediated by the expression of Fas and activation of caspase-8, caspase-3, and poly (ADP-ribose) polymerase. Immunoblotting showed downregulation of the anti-apoptotic mitochondrial proteins Bcl-2 and Bcl-xL, but upregulationof the mitochondria-dependent pro-apoptotic proteins Bax and Badin FaDu cells after acacetin treatment. Thesefindings indicate that acacetin inhibits cell proliferation and induces apoptotic cell death in FaDu human pharyngealcarcinoma cells via both the death receptor-mediated extrinsic apoptotic pathway and the mitochondria-mediatedintrinsic apoptotic pathway.
참고문헌 (29)
- Saman Warnakulasuriya, "Global epidemiology of oral and oropharyngeal cancer", Oral Oncology, 45(4-5), pp.309~316 (2009), Elsevier BV[DOI]
- Nicholas Kalavrezos, "Mouth cancer for clinicians part 2: epidemiology", Dental Update, 42(4), pp.354~359 (2015), Mark Allen Group[DOI]
- Fenglin Sun, "Acacetin‐induced cell apoptosis in head and neck squamous cell carcinoma cells: Evidence for the role of muscarinic M3 receptor", Phytotherapy Research, 33(5), pp.1551~1561 (2019), Wiley[DOI]
- Eleni M. Rettig, "Epidemiology of Head and Neck Cancer", Surgical Oncology Clinics of North America, 24(3), pp.379~396 (2015), Elsevier BV[DOI]
- Francesca Pezzuto, "Update on Head and Neck Cancer: Current Knowledge on Epidemiology, Risk Factors, Molecular Features and Novel Therapies", Oncology, 89(3), pp.125~136 (2015), S. Karger AG[DOI]
- S. K. Kundu, "Targeted therapy in head and neck cancer", Tumor Biology, 33(3), pp.707~721 (2012), Springer Science and Business Media LLC[DOI]
- Peter G. Sacks, "Cell, tissue and organ culture as in vitro models to study the biology of squamous cell carcinomas of the head and neck", Cancer and Metastasis Review, 15(1), pp.27~51 (1996), Springer Science and Business Media LLC[DOI]
- Randy Todd, "The molecular biology of oral carcinogenesis: Toward a tumor progression model", Journal of Oral and Maxillofacial Surgery, 55(6), pp.613~623 (1997), Elsevier BV[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]
- D. R. Green and John C. Reed, "Mitochondria and Apoptosis", Science, 281(5381), pp.1309~1312 (1998), American Association for the Advancement of Science (AAAS)[DOI]
- Michael O. Hengartner, "The biochemistry of apoptosis", Nature, 407(6805), pp.770~776 (2000), Springer Science and Business Media LLC[DOI]
- Scott H. Kaufmann, "Programmed cell death: alive and well in the new millennium", Trends in Cell Biology, 11(12), pp.526~534 (2001), Elsevier BV[DOI]
- Gerald M. COHEN, "Caspases: the executioners of apoptosis", Biochemical Journal, 326(1), pp.1~16 (1997), Portland Press Ltd[DOI]
- Wei Hu, "Anticancer therapy targeting the apoptotic pathway", The Lancet Oncology, 4(12), pp.721~729 (2003), Elsevier BV[DOI]
- 정경인, "Inhibition of cell growth and induction of apoptosis by bilobalide in FaDu human pharyngeal squamous cell carcinoma", International Journal of Oral Biology, 45(1), pp.8~14 (2020), 대한구강생물학회
- Scott H. Kaufmann, "Induction of Apoptosis by Cancer Chemotherapy", Experimental Cell Research, 256(1), pp.42~49 (2000), Elsevier BV[DOI]
- John C Reed, "Apoptosis-regulating proteins as targets for drug discovery", Trends in Molecular Medicine, 7(7), pp.314~319 (2001), Elsevier BV[DOI]
- Reenu Punia, "Acacetin enhances the therapeutic efficacy of doxorubicin in non-small-cell lung carcinoma cells", PLOS ONE, 12(8), pp.e0182870~ (2017), Public Library of Science (PLoS)[DOI]
- Tariq A. Bhat, "Acacetin inhibits in vitro and in vivo angiogenesis and downregulates Stat signaling and VEGF expression", Cancer Prevention Research, 6(10), pp.1128~1139 (2013), American Association for Cancer Research (AACR)[DOI]
- Harish Chandra Pal, "Phytochemicals for the Management of Melanoma", Mini-Reviews in Medicinal Chemistry, 16(12), pp.953~979 (2016), Bentham Science Publishers Ltd[DOI]
- 조지호, "MicroRNA-27 Promotes Odontoblast Differentiation via Wnt1 Signaling", International Journal of Oral Biology, 40(4), pp.197~204 (2015), 대한구강생물학회[DOI]
- C. Herrnring, "Expression of the apoptosis-inducing ligands FasL and TRAIL in malignant and benign human breast tumors", Histochemistry and Cell Biology, 113(3), pp.189~194 (2000), Springer Science and Business Media LLC[DOI]
- H.-J. Li, "FasL-induced apoptosis in bovine oocytes via the Bax signal", Theriogenology, 80(3), pp.248~255 (2013), Elsevier BV[DOI]
- Ze Tian, "The cytotoxicity of naturally occurring styryl lactones", Phytomedicine, 13(3), pp.181~186 (2006), Elsevier BV[DOI]
- Rakesh Datta, "Caspase-3-mediated Cleavage of Protein Kinase C θ in Induction of Apoptosis", Journal of Biological Chemistry, 272(33), pp.20317~20320 (1997), Elsevier BV[DOI]
- Xuesong Liu, "DFF, a Heterodimeric Protein That Functions Downstream of Caspase-3 to Trigger DNA Fragmentation during Apoptosis", Cell, 89(2), pp.175~184 (1997), Elsevier BV[DOI]
- SEOK-JIN YANG, "Induction of apoptosis by diphenyldifluoroketone in osteogenic sarcoma cells is associated with activation of caspases", Oncology Reports, 31(5), pp.2286~2292 (2014), Spandidos Publications[DOI]
- R. M. Kluck, "The Release of Cytochrome c from Mitochondria: A Primary Site for Bcl-2 Regulation of Apoptosis", Science, 275(5303), pp.1132~1136 (1997), American Association for the Advancement of Science (AAAS)[DOI]
- Ruth M. Kluck, "The Pro-Apoptotic Proteins, Bid and Bax, Cause a Limited Permeabilization of the Mitochondrial Outer Membrane That Is Enhanced by Cytosol", Journal of Cell Biology, 147(4), pp.809~822 (1999), Rockefeller University Press[DOI]