Author(s): Lu, HF (Lu, Hsu-Feng); Chen, YS (Chen, Yi-Shan); Yang, JS (Yang, Jai-Sing);
Chen, JC (Chen, Jung-Chou); Lu, KW (Lu, Kung-Wen); Chiu, TH (Chiu, Tsan-Hung); Liu, KC (Liu, Kuo-Ching); Yeh, CC (Yeh, Chin-Chung); Chen, GW (Chen, Guang-Wei); Lin, HJ (Lin, Hui-Ju); Chung, JG (Chung, Jing-Gung)
Title: Gypenosides induced G0/G1 arrest via inhibition of cyclin e and induction of apoptosis via activation of caspases-3 and-9 in human lung cancer A-549 cells
Source: IN VIVO, 22 (2): 215-221 MAR-APR 2008 Language: English
Document Type: Article
Author Keywords: gypenosides; apoptosis; caspase-3; Bcl-2; Bax; p53; cell; cycle
KeyWords Plus: GYNOSTEMMA-PENTAPHYLLUM; ANOECTOCHILUS-FORMOSANUS;
N-ACETYLTRANSFERASE; ADDUCT FORMATION; CARCINOMA-CELLS; LEUKEMIA- CELLS; BCL-2; P53; EXPRESSION; ANTIOXIDANT
Abstract: Gynostemma pentaphyllum Makino is known in Asia for its effect on the treatment of hepatitis and cardiovascular diseases. Gypenosides (Gyp) are the major components extracted from Gynostemma pentaphyllum Makino. However, the molecular mechanism underlying the Gyp-induced cell cycle arrest and apoptotic process is unclear. In this study, the chemopreventive role of Gyp in human lung cancer (A549) cells in vitro was evaluated by studying the regulation of the cell cycle and apoptosis. Gyp induced G0/G1 arrest and apoptosis in the human lung cancer A549 cells. Investigation of the cyclin-dependent protein kinase inhibitors by Western blotting showed that p16, p21, p27 and p53 proteins were increased with the increasing time of incubation with. Gyp in the A549 cells. This increase may be the major factor by which Gyp caused G0/G1 arrest in the examined cells. Flow cytometric assay and gel electrophoresis of DNA fragmentation also confirmed that Gyp induced
apoptosis in the A549 cells. Our data demonstrated that Gyp-induced apoptotic cell death was accompanied by up-regulation of Bax, caspase-3 and caspase-9, but down-regulation of the Bcl-2 levels. Taken together, Gyp appears to exert its anticancer properties by inducing G0/G1-phase arrest and apoptosis via activation of caspase-3 in human lung A549 cancer cells.
Addresses: [Chen, Yi-Shan; Chung, Jing-Gung] China Med Univ, Dept Biol Sci & Technol, Taichung 404, Taiwan; [Lu, Hsu-Feng] Cheng Hsin Rehabil Med Ctr, Dept Clin Pathol, Taipei, Taiwan; [Yang, Jai-Sing] China Med Univ, Dept Pharmacol, Taichung 404, Taiwan; [Chen, Jung-Chou; Lu, Kung-Wen] China Med Univ, Chinese Med Res Inst, Taichung 404, Taiwan;
[Liu, Kuo-Ching] China Med Univ, Sch Med Lab Sci & Biotechnol, Taichung 404, Taiwan;
[Chiu, Tsan-Hung] China Med Univ Hosp, Dept OBS, Taichung, Taiwan; [Yeh, Chin-Chung]
China Med Univ Hosp, Dept Urol, Taichung, Taiwan; [Lin, Hui-Ju] China Med Univ Hosp, Dept Ophthalmol, Taichung, Taiwan; [Chen, Guang-Wei] Kaohsiung Med Univ, Chung Ho Mem
Hosp, Dept Tradit Chinese Med, Kaohsiung, Taiwan; [Chung, Jing-Gung] Asia Univ, Dept Biotechnol, Taichung, Taiwan
Reprint Address: Chung, JG, China Med Univ, Dept Biol Sci & Technol, 91 Hsueh Shih Rd, Taichung 404, Taiwan.
E-mail Address: [email protected]
Cited References: ARMENGOL C, 2003, J HEPATOL, V38, P591, DOI 10.1016/S0168- 8278(03)00025-4.
BULLOCK AN, 2001, NAT REV CANCER, V1, P68.
CHEN JC, 2006, ANTICANCER RES, V26, P4313.
CHIU TH, 2003, IN VIVO, V17, P281.
CHUNG JG, 2000, AM J CHINESE MED, V28, P227.
GENG Y, 1999, CELL, V97, P767.
GUADAGNO TM, 1996, CELL, V84, P73.
HENGARTNER MO, 1994, CELL, V76, P665.
HOU J, 1991, J TRADIT CHIN MED, V11, P47.
HU LH, 1996, J NAT PROD, V59, P1143.
KATNER AL, 2002, PROSTATE, V53, P77, DOI 10.1002/pros.10124.
KERR JFR, 1994, CANCER, V73, P2013.
KO LJ, 1996, GENE DEV, V10, P1054.
LACOUR B, 1995, J ETHNOPHARMACOL, V46, P125.
LEE M, 2001, FREE RADICAL BIO MED, V31, P1550.
LI L, 1993, CANCER BIOTHERAPY, V8, P263.
LILENBAUM RC, 1993, J CLIN ONCOL, V11, P1391.
LIN CC, 2000, AM J CHINESE MED, V28, P87.
LIN CC, 2006, ANTICANCER RES, V26, P1097.
LIN JM, 1993, AM J CHINESE MED, V21, P59.
OLTVAI ZN, 1993, CELL, V74, P619.
OLTVAI ZN, 1994, CELL, V79, P189.
PEZZUTO JM, 1997, BIOCHEM PHARMACOL, V53, P121.
PURMOVA J, 1995, CESKA SLOVENSKA FARM, V44, P246.
RIEBER M, 2003, BIOCHEM PHARMACOL, V65, P1593, DOI 10.1016/S0006- 2952(03)00147-3.
SLATER EP, 2003, INT J CANCER, V104, P425, DOI 10.1002/ijc.10983.
SLEE EA, 2004, ONCOGENE, V23, P2809, DOI 10.1038/sj.onc.1207516.
SU CC, 2006, ANTICANCER RES, V26, P1281.
TAN H, 1993, CHUNG KUO CHUNG HSI, V13, P278.
TANG NY, 2006, IN VIVO, V20, P527.
WAHL GM, 2001, NAT CELL BIOL, V3, E277.
WANG C, 1995, HUAXI YIKE DAXUE XUE, V26, P430.
WANG QF, 2002, CANCER LETT, V183, P169.
YANG RM, 1998, J UROLOGY, V159, P941.
YU R, 1996, CHUNG KUO CHUNG HSI, V16, P470.
ZHOU Z, 1996, ZHONGHUA KOU QIANG Y, V31, P267.
Cited Reference Count: 36 Times Cited: 9
Publisher: INT INST ANTICANCER RESEARCH
Publisher Address: EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE
ISSN: 0258-851X
29-char Source Abbrev.: IN VIVO ISO Source Abbrev.: In Vivo Source Item Page Count: 7
Subject Category: Medicine, Research & Experimental ISI Document Delivery No.: 286NG