Hedyotis Diffusa Willd extract induces apoptosis via activation of the mitochondrion-dependent pathway in human colon carcinoma cells

被引:99
作者
Lin, Jiumao [1 ]
Chen, Youqin [3 ,4 ]
Wei, Lihui [1 ]
Chen, Xuzhen [1 ]
Xu, Wei [2 ]
Hong, Zhenfeng [1 ]
Sferra, Thomas J. [3 ,4 ]
Peng, Jun [1 ]
机构
[1] Fujian Univ Tradit Chinese Med, Fujian Acad Integrat Med, Fuzhou 350108, Fujian, Peoples R China
[2] Fujian Univ Tradit Chinese Med, Dept Pharmacol, Fuzhou 350108, Fujian, Peoples R China
[3] Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA
[4] Univ Oklahoma, Hlth Sci Ctr, Dept Biochem & Mol Biol, Oklahoma City, OK 73190 USA
关键词
apoptosis; colorectal cancer; HT-29; cells; herbal medicine; mitochondria; Hedyotis Diffusa Willd; MULTICENTER RANDOMIZED-TRIAL; METASTATIC COLORECTAL-CANCER; CHANNEL-FORMING ACTIVITY; CYTOCHROME-C; 1ST-LINE TREATMENT; BCL-2; BAX; RELEASE; FAMILY; DEATH;
D O I
10.3892/ijo_00000785
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Hedyotis Diffusa Willd has been used as a major component in several Chinese medicine formulations for the clinical treatment of colorectal cancer. However, the molecular mechanism of the anti-cancer activity of Hedyotis Diffusa Wind remains unclear. In the present study, we investigated the cellular effects of the ethanol extract of Hedyotis Diffusa Willd (EEHDW) in the HT-29 human colon carcinoma cell line. We found that EEHDW inhibited the growth of HT-29 cells demonstrating EEHDW-induced cell morphological changes and reduced cell viability in a dose- and time-dependent manner. Furthermore, we observed that EEHDW treatment resulted in DNA fragmentation, loss of plasma membrane asymmetry, collapse of mitochondrial membrane potential, activation of caspase-9 and caspase-3, and increase of the ratio of pro-apoptotic Bax to anti-apoptotic suggesting that the HT-29 cell growth inhibitory activity of EEHDW was clue to mitochondrion-mediated apoptosis, which may partly explain the anti-cancer activity of Hedyotis Diffusa Willd.
引用
收藏
页码:1331 / 1338
页数:8
相关论文
共 34 条
[1]   The Bcl-2 apoptotic switch in cancer development and therapy [J].
Adams, J. M. ;
Cory, S. .
ONCOGENE, 2007, 26 (09) :1324-1337
[2]   Bax oligomerization is required for channel-forming activity in liposomes and to trigger cytochrome c release from mitochondria [J].
Antonsson, B ;
Montessuit, S ;
Lauper, S ;
Eskes, R ;
Martinou, JC .
BIOCHEMICAL JOURNAL, 2000, 345 :271-278
[3]   Inhibition of Bax channel-forming activity by Bcl-2 [J].
Antonsson, B ;
Conti, F ;
Ciavatta, A ;
Montessuit, S ;
Lewis, S ;
Martinou, I ;
Bernasconi, L ;
Bernard, A ;
Mermod, JJ ;
Mazzei, G ;
Maundrell, K ;
Gambale, F ;
Sadoul, R ;
Martinou, JC .
SCIENCE, 1997, 277 (5324) :370-372
[4]   Genotoxicity of several clinically used topoisomerase II inhibitors [J].
Boos, G ;
Stopper, H .
TOXICOLOGY LETTERS, 2000, 116 (1-2) :7-16
[5]   The BCL2 family: Regulators of the cellular life-or-death switch [J].
Cory, S ;
Adams, JM .
NATURE REVIEWS CANCER, 2002, 2 (09) :647-656
[6]   Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial [J].
Douillard, JY ;
Cunningham, D ;
Roth, AD ;
Navarro, M ;
James, RD ;
Karasek, P ;
Jandik, P ;
Iveson, T ;
Carmichael, J ;
Alakl, M ;
Gruia, G ;
Awad, L ;
Rougier, P .
LANCET, 2000, 355 (9209) :1041-1047
[7]   Phase III multicenter randomized trial of oxaliplatin added to chronomodulated fluorouracil-leucovorin as first-line treatment of metastatic colorectal cancer [J].
Giacchetti, S ;
Perpoint, B ;
Zidani, R ;
Le Bail, N ;
Faggiuolo, R ;
Focan, C ;
Chollet, P ;
Llory, JF ;
Letourneau, Y ;
Coudert, B ;
Bertheaut-Cvitkovic, F ;
Larregain-Fournier, D ;
Le Rol, A ;
Walter, S ;
Adam, R ;
Misset, JL ;
Lévi, F .
JOURNAL OF CLINICAL ONCOLOGY, 2000, 18 (01) :136-147
[8]   BCL-2 family members and the mitochondria in apoptosis [J].
Gross, A ;
McDonnell, JM ;
Korsmeyer, SJ .
GENES & DEVELOPMENT, 1999, 13 (15) :1899-1911
[9]   Cytosol-to-membrane redistribution of Bax and Bcl-X-L during apoptosis [J].
Hsu, YT ;
Wolter, KG ;
Youle, RJ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3668-3672
[10]   Anticancer activities of pomegranate extracts and genistein in human breast cancer cells [J].
Jeune, MAL ;
Kumi-Diaka, J ;
Brown, J .
JOURNAL OF MEDICINAL FOOD, 2005, 8 (04) :469-475