Anticancer effects of quercetin on KB human oral cancer cells
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Purpose: The main aim of this study was to determine the effects of quercetin (3,5,7,3',4'-tetrahydroxyflavone) and rutin (quercetin-3-O-rutinoside) on the induction of cell growth and apoptosis in human oral cancer cells. Materials and Methods: The effects of quercetin and rutin on cell growth and apoptosis induction in human oral cancer cells were examined using a MTT assay, nuclear staining with DAPI, immunoblotting and a determination of caspase activation in KB human oral cancer cells. Results: Quercetin inhibited the growth of KB cells in a concentration- and time-dependent manner but rutin did not have a significant effect on the cell viability of KB cells. Treatment of KB cells with quercetin resulted in nuclear condensation and fragmentation, whereas rutin had little effect on nuclear condensation and fragmentation. Quercetin time-dependently promoted the proteolytic cleavage of procaspase-3 in KB cells with increasing amounts of cleaved caspase-3. On the other hand,rutin did not promote signifi cant proteolytic cleavage of procaspase-3. The proteolytic processing of caspase-7 in KB cells was increased by quercetin but not by rutin. Quercetin promoted the proteolytic cleavage of procaspase-9 with increases in the amount of cleaved caspase-9, whereas rutin did not. The activation of caspase-3 and -7 in living KB cells treated with quercetin was detected by fl uorescence microscopy but rutin did not lead to signifi cant caspase-3/-7 activation in the cells. Conclusion: Quercetin strongly inhibits cell proliferation and induces apoptosis in KB human oral cancer cells, and might have potential properties for anti oral cancer drug discovery.
Abstract
Purpose: The main aim of this study was to determine the effects of quercetin (3,5,7,3',4'-tetrahydroxyflavone) and rutin (quercetin-3-O-rutinoside) on the induction of cell growth and apoptosis in human oral cancer cells. Materials and Methods: The effects of quercetin and rutin on cell growth and apoptosis induction in human oral cancer cells were examined using a MTT assay, nuclear staining with DAPI, immunoblotting and a determination of caspase activation in KB human oral cancer cells. Results: Quercetin inhibited the growth of KB cells in a concentration- and time-dependent manner but rutin did not have a significant effect on the cell viability of KB cells. Treatment of KB cells with quercetin resulted in nuclear condensation and fragmentation, whereas rutin had little effect on nuclear condensation and fragmentation. Quercetin time-dependently promoted the proteolytic cleavage of procaspase-3 in KB cells with increasing amounts of cleaved caspase-3. On the other hand,rutin did not promote signifi cant proteolytic cleavage of procaspase-3. The proteolytic processing of caspase-7 in KB cells was increased by quercetin but not by rutin. Quercetin promoted the proteolytic cleavage of procaspase-9 with increases in the amount of cleaved caspase-9, whereas rutin did not. The activation of caspase-3 and -7 in living KB cells treated with quercetin was detected by fl uorescence microscopy but rutin did not lead to signifi cant caspase-3/-7 activation in the cells. Conclusion: Quercetin strongly inhibits cell proliferation and induces apoptosis in KB human oral cancer cells, and might have potential properties for anti oral cancer drug discovery.
참고문헌 (45)
- Alía M, "Influence of quercetin and rutin on growth and antioxidant defense system of a human hepatoma cell line (HepG2)", Eur J Nutr, 45, pp.19~28 (2006)
- Cheng YL, "Anti-proliferative activity of Bupleurum scrozonerifolium in A549 human lung cancer cells in vitro and in vivo", Cancer Lett, 222, pp.183~193 (2005)
- 이희구, "Indole-3-carbinol induces apoptosis through p53 and activation of caspase-8 pathway in lung cancer A549 cells", FOOD AND CHEMICAL TOXICOLOGY, 48, pp.883~890, PERGAMON-ELSEVIER SCIENCE LTD
- Christou L, "Treatment of plasma cell leukemia with vincristine, liposomal doxorubicin and dexamethasone", Eur J Haematol, 67, pp.51~53 (2001)
- Cohen GM, "Caspases: the executioners of apoptosis", Biochem J, 326, pp.1~16 (1997)
- Datta R, "Caspase-3-mediated cleavage of protein kinase C theta in induction of apoptosis", J Biol Chem, 272, pp.20317~20320 (1997)
- Green DR, "Mitochondria and apoptosis", Science, 281, pp.1309~1312 (1998)
- Hengartner MO, "The biochemistry of apoptosis", Nature, 407, pp.770~776 (2000)
- Hoshino T, "Flow cytometric measurement of NK cell cytotoxicity", J Clin Lab Immunol, 36, pp.39~43 (1991)
- Hu W, "Anticancer therapy targeting the apoptotic pathway", Lancet Oncol, 4, pp.721~729 (2003)
- Hae-Ryong Park, "Effect of Methanolic Extract from Silkworm Droppings on Proliferation and Caspase Activity in HT-29 Human Colon Cancer Cells", Journal of Medicinal Food, 10(3), pp.467~472 (2007), 한국식품영양과학회
- Janbaz KH, "Protective effect of rutin on paracetamol- and CCl4-induced hepatotoxicity in rodents", Fitoterapia, 73, pp.557~563 (2002)
- Joyeux M, "tert-Butyl hydroperoxide-induced injury in isolated rat hepatocytes: a model for studying anti-hepatotoxic crude drugs", Planta Med, 56, pp.171~174 (1990)
- Kaufmann SH, "Induction of apoptosis by cancer chemotherapy", Exp Cell Res, 256, pp.42~49 (2000)
- Kaufmann SH, "Programmed cell death: alive and well in the new millennium", Trends Cell Biol, 11, pp.526~534 (2001)
- Kim CS, "BCH, an inhibitor of system L amino acid transporters, induces apoptosis in cancer cells", Biol Pharm Bull, 31, pp.1096~1100 (2008)
- 문정용, "Induction of apoptosis in human cervical carcinoma HeLa cells by polymethoxylated flavone-rich Citrus grandis Osbeck (Dangyuja) leaf extract", FOOD AND CHEMICAL TOXICOLOGY, 48, pp.2435~2442, PERGAMON-ELSEVIER SCIENCE LTD
- Kuo SM, "Antiproliferative potency of structurally distinct dietary fl avonoids on human colon cancer cells", Cancer Lett, 110, pp.41~48 (1996)
- Jae Im Kwon, "Induction of Apoptosis by Linoleic Acid Is Associated with the Modulation of Bcl-2 Family and Fas", FasL System and Activation of Caspases in AGS Human Gastric Adenocarcinoma Cells, 2008, pp.11(1), 1~8[DOI]
- Lima CF, "Phenolic compounds protect HepG2 cells from oxidative damage: relevance of glutathione levels", Life Sci, 79, pp.2056~2068 (2006)
- Lin CW, "Quercetin inhibition of tumor invasion via suppressing PKC delta", ERK, Carcinogenesis, pp.2008, 29[DOI]
- Liu J, "Pharmacology of oleanolic acid and ursolic acid", J Ethnopharmacol, 49, pp.57~68 (1995)
- Liu X, "DFF, a heterodimeric protein that functions downstream of caspase-3 to trigger DNA fragmentation during apoptosis", Cell, 89, pp.175~184 (1997)
- Lotito SB, "Dietary flavonoids attenuate tumor necrosis factor alpha-induced adhesion molecule expression in human aortic endothelial cells. Structure-function relationships and activity after first pass metabolism", J Biol Chem, 281, pp.37102~37110 (2006)
- Mamani-Matsuda M, "Therapeutic and preventive properties of quercetin in experimental arthritis correlate with decreased macrophage infl ammatory mediators", Biochem Pharmacol, 72, pp.1304~1310 (2006)
- Martin-Aragón S, "Pharmacological modification of endogenous antioxidant enzymes by ursolic acid on tetrachloride-induced liver damage in rats and primary cultures of rat hepatocytes", Exp Toxicol Pathol, 53, pp.199~206 (2001)
- Mukherjee AK, "Advances in cancer therapy with plant based natural products", Curr Med Chem, 8, pp.1467~1486 (2001)
- Naderi GA, "Anti-oxidant effect of flavonoids on the susceptibility of LDL oxidation", Mol Cell Biochem, 246, pp.193~196 (2003)
- Nichenametla SN, "A review of the effects and mechanisms of polyphenolics in cancer", Crit Rev Food Sci Nutr, 46, pp.161~183 (2006)
- Notani PN, "Epidemiology and prevention of head and neck cancer: a global view, In Contemporary issues in oral cancer", pp.1~29 (2000), Oxford University Press
- Novotný L, "Ursolic acid: an anti-tumorigenic and chemopreventive activity. Minireview", Neoplasma, 48, pp.241~246 (2001)
- Park DI, "Induction of apoptosis and inhibition of telomerase activity by aqueous extract from Platycodon grandifl orum in human lung carcinoma cells", Pharmacol Res, 51, pp.437~443 (2005)
- Paschka AG, "Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin-3-gallate", Cancer Lett, 130, pp.1~7 (1998)
- Pezzuto JM, "Plant-derived anticancer agents", Biochem Pharmacol, 3, pp.121~133 (1997)
- Ramos AA, "Antigenotoxic effects of quercetin, rutin and ursolic acid on HepG2 cells: evaluation by the comet assay", Toxicol Lett, 177, pp.66~73 (2008)
- Reed JC, "Apoptosis-regulating proteins as targets for drug discovery", Trends Mol Med, 7, pp.314~319 (2001)
- Smets LA, "Programmed cell death (apoptosis) and response to anti-cancer drugs", Anticancer Drugs, 5, pp.3~9 (1994)
- Tan ML, "Methanolic extract of Pereskia bleo (Kunth) DC. (Cactaceae) induces apoptosis in breast carcinoma, T47-D cell line", J Ethnopharmacol, 96, pp.287~294 (2005)
- Tan X, "Multiple anticancer activities of EF24, a novel curcumin analog, on human ovarian carcinoma cells", Reprod Sci, 17, pp.931~940 (2010)
- Tian Z, "The cytotoxicity of naturally occurring styryl lactones", Phytomedicine, 13, pp.181~186 (2006)
- Tian Z, "Antihepatoma activity and mechanism of ursolic acid and its derivatives isolated from Aralia decaisneana", World J Gastroenterol, 12, pp.874~879 (2006)
- Todd R, "The molecular biology of oral carcinogenesis: toward a tumor progression model", J Oral Maxillofac Surg, 55, pp.613~623 (1997)
- van Poppel G, "Vitamins and cancer", Cancer Lett, 114, pp.195~202 (1997)
- Zhang X, "Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells through inducing apoptosis via decreasing Bcl-2 expression", Clin Exp Metastasis, 18, pp.415~421 (2000)
- Zhang XM, "Quercetin inhibits the invasion of murine melanoma B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway", Cancer Chemother Pharmacol, 53, pp.82~88 (2004)