Abstract
The fruits of Chaenomeles sinensis have numerous therapeutic properties, including anticancer and antiinflammatory activities; however, its antitumor activity and underlying molecular mechanism are poorly understood. The present study evaluated the in vitro and in vivo antitumor activities of a fraction of C. sinensis extract purified on amberlite resin and eluted in 30% methanol (CSAM 30). In vitro, cell viability was assessed using the CCK-8 assay, cell cycle was analyzed by flow cytometry, and apoptosis was measured by Hoechst DNA staining, caspase activity assays and Western blotting. In vivo antitumor efficacy of CSAM 30 was evaluated by oral administration on the human HepG2 hepatocellular carcinoma preclinical xenograft model. In vitro, CSAM 30 inhibited HepG2 cell proliferation and induced apoptosis via activation of caspases, cleavage of poly ADP-ribose polymerase, up-regulation of Bad, and down-regulation of Xlinked inhibitor of apoptosis protein XIAP and bcl-2. In vivo, CSAM 30 inhibited HepG2 tumor growth in a dose-dependent manner without inducing body weight loss. These results demonstrate that CSAM 30 induces apoptosis and has antitumor activity in vivo and in vitro.
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Banno N, Akihisa T, Tokuda H, Yasukawa K, Higashihara H, Ukiya M et al. (2004) Triterpene acids from the leaves of Perilla frutescens and their anti-inflammatory and antitumor-promoting effects. Biosci Biotechnol Biochem 68, 85–90.
Bosch FX, Ribes J, Díaz M, and Cléries R (2004) Primary liver cancer: Worldwide incidence and trends. Gastroenterology 127, S5–S16.
Chen W, Hou J, Yin Y, Jang J, Zheng Z, Fan H et al. (2010) alpha-Bisabolol induces dose- and time-dependent apoptosis in HepG2 cells via a Fasand mitochondrial-related pathway, involves p53 and NFkappaB. Biochem Pharmacol 80, 247–254.
Fulda S and Debatin KM (2000) Betulinic acid induces apoptosis through a direct effect on mitochondria in neuroectodermal tumors. Med Pediatr Oncol 35, 616–618.
Fulda S, Jeremis I, Pietsch T, and Debatin KM (1999) Betulinic acid: a new chemotherapeutic agent in the treatment of neuroectodermal tumors. Klin Padiatr 211, 319–322.
Gao H, Wu L, Kuroyanagi M, Harada K, Kawahara N, Nakane T et al. (2003) Antitumor-promoting constituents from Chaenomeles sinensis KOEHNE and their activities in JB6 mouse epidermal cells. Chem Pharm Bull (Tokyo) 51, 1318–1321.
Ghobrial IM, Witzig TE, and Adjei AA (2005) Targeting apoptosis pathways in cancer therapy. CA Cancer J Clin 55, 178–194.
Gomaa AI, Khan SA, Toledano MB, Waked I, and Taylor-Robinson SD (2008) Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. World J Gastroenterol 14, 4300–4308.
Hamauzu Y, Yasui H, Inno T, Kume C, and Omanyuda M (2005) Phenolic profile, antioxidant property, and anti-influenza viral activity of Chinese quince (Pseudocydonia sinensis Schneid.), quince (Cydonia oblonga Mill.), and apple (Malus domestica Mill.) fruits. J Agric Food Chem 53, 928–934.
Igney FH and Krammer PH (2002) Death and anti-death: Tumour resistance to apoptosis. Nat Rev Cancer 2, 277–288.
Kamesaki H (1998) Mechanisms involved in chemotherapy-induced apoptosis and their implications in cancer chemotherapy. Int J Hematol 68, 29–43.
Kaufmann SH and Earnshaw WC (2000) Induction of apoptosis by cancer chemotherapy. Exp Cell Res 256, 42–49.
Kelloff GJ, Crowell JA, Steele VE, Lubet RA, Malone WA, Boone CW et al. (2000) Progress in cancer chemoprevention: Development of dietderived chemopreventive agents. J Nutr 130, 467S–4671S.
Kolenko VM, Uzzo RG, Bukowski R, and Finke JH (2000) Caspase-dependent and -independent death pathways in cancer therapy. Apoptosis 5, 17–20.
Li Y, Ahmed F, Ali S, Philip PA, Kucuk O, and Sarkar FH (2005) Inactivation of nuclear factor kappaB by soy isoflavone genistein contributes to increased apoptosis induced by chemotherapeutic agents in human cancer cells. Cancer Res 65, 6934–6942.
Mao CY, Hua HJ, Chen P, Yu DC, Cao J, and Teng LS (2009) Combined use of chemotherapeutics and oncolytic adenovirus in treatment of AFPexpressing hepatocellular carcinoma. Hepatobiliary Pancreat Dis Int 8, 282–287.
Oku H, Ueda Y, and Ishiguro K (2003) Antipruritic effects of the fruits of Chaenomeles sinensis. Biol Pharm Bull 26, 1031–1034.
Pan MH, Ghai G, and Ho CT (2008) Food bioactives, apoptosis, and cancer. Mol Nutr Food Res 52, 43–52.
Parkin DM, Bray F, Ferlay J, and Pisani P (2001) Estimating the world cancer burden: Globocan. Int J Cancer 94, 153–156.
Sancheti S, Sancheti S, and Seo SY (2009) Chaenomeles Sinensis: A Potent α-and β-Glucosidase Inhibitor. Am J Pharm & Toxicol 4, 8–11.
Sawai R, Kuroda K, Shibata T, Gomyou R, Osawa K, and Shimizu K (2008) Anti-influenza virus activity of Chaenomeles sinensis. J Ethnopharmacol 118, 108–112.
Scovassi AI and Poirier GG (1999) Poly(ADP-ribosylation) and apoptosis. Mol Cell Biochem 199, 125–137.
Shi Y (2002) Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell 9, 459–470.
Sodhi RK, Singh N, and Jaggi AS (2010) Poly(ADP-ribose) polymerase-1 (PARP-1) and its therapeutic implications. Vascul Pharmacol 53, 77–87.
Talanian RV, Quinlan C, Trautz S, Hackett MC, Mankovich JA, Banach D et al. (1997) Substrate specificities of caspase family proteases. J Biol Chem 272, 9677–9682.
Verhagen AM, Silke J, Ekert PG, Pakusch M, Kaufmann H, Connolly LM et al. (2002) HtrA2 promotes cell death through its serine protease activity and its ability to antagonize inhibitor of apoptosis proteins. J Biol Chem 277, 445–454.
Wang H, Li H, Zuo M, Zhang Y, Liu H, Fang W et al. (2008) Lx2-32c, a novel taxane and its antitumor activities in vitro and in vivo. Cancer Lett 268, 89–97.
World Health Organization Regional Office for the Western Pacific (1998) Medicinal plants in the Republic of Korea: information on 150 commonly used medicinal plants/compiled by Natural Products Research Institute, pp. 63, Seoul National University.
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Chun, J.M., Nho, K.J., Lee, A.Y. et al. A methanol fraction from Chaenomeles sinensis inhibits hepatocellular carcinoma growth in vitro and in vivo . J Korean Soc Appl Biol Chem 55, 335–341 (2012). https://doi.org/10.1007/s13765-012-1043-7
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DOI: https://doi.org/10.1007/s13765-012-1043-7