Isoalantolactone, a sesquiterpene lactone, induces apoptosis in SGC-7901 cells via mitochondrial and phosphatidylinositol 3-kinase/Akt signaling pathways

被引:51
作者
Rasul, Azhar [1 ]
Khan, Muhammad [1 ]
Yu, Bo [2 ]
Ali, Muhammad [3 ]
Bo, Yang Jing [1 ]
Yang, Hong [2 ]
Ma, Tonghui [1 ,2 ]
机构
[1] Jilin Univ Bethune Second Hosp, Cent Res Lab, Changchun 130041, Peoples R China
[2] Liaoning Normal Univ, Sch Life Sci, Dalian 116029, Peoples R China
[3] Bahauddin Zakariya Univ, Inst Biotechnol, Multan 60800, Pakistan
关键词
Isoalantolactone; Sesquiterpene lactone; SGC-7901; cells; Apoptosis; PI3K/Akt pathway; BCL-2 FAMILY PROTEINS; GASTRIC-CANCER CELLS; NF-KAPPA-B; CYCLE ARREST; INULA-RACEMOSA; ANTICANCER AGENTS; INDUCTION; DEATH; INHIBITION; CHECKPOINTS;
D O I
10.1007/s12272-013-0217-0
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Isoalantolactone, a sesquiterpene lactone, possesses anti-fungal as well as cytotoxic properties. In this study, the effects of Isoalantolactone on cell viability, cell cycle, and apoptosis were investigated in human gastric adenocarcinoma SGC-7901 cells. The results demonstrated that Isoalantolactone induced morphological changes and decreased cell viability. Subsequently, we found that Isoalantolactone induced G2/M and S phase arrest, which was associated with a decrease in the expression level of cyclin B1. Apoptosis triggered by Isoalantolactone was visualized using propidium iodide (PI) and Annexin V-FITC/PI staining. Isoalantolactone-induced apoptosis of SGC-7901 cells was associated with the dissipation of mitochondrial membrane potential (Delta I (m)) that was due to the down-regulation of Bcl-2 and up-regulation of Bax that led to the cleavage of caspase-3. Additionally, it was found that Isoalantolactone was involved in the inhibition of phosphorylation of PI3K/Akt. Isoalantolactone-induced cytotoxicity and apoptosis of SGC-7901 cells involve mitochondria-caspase and PI3K/Akt dependent pathways, which gives the rationale for in vivo studies on the utilization of Isoalantolactone as a potential cancer therapeutic compound.
引用
收藏
页码:1262 / 1269
页数:8
相关论文
共 45 条
[31]   Berberine, a natural product, induces G1-phase cell cycle arrest and caspase-3-dependent apoptosis in human prostate carcinoma cells [J].
Mantena, SK ;
Sharma, SD ;
Katiyar, SK .
MOLECULAR CANCER THERAPEUTICS, 2006, 5 (02) :296-308
[32]   Naturally occurring NF-κB inhibitors [J].
Nam, Nguyen-Hai .
MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2006, 6 (08) :945-951
[33]   Caspase structure, proteolytic substrates, and function during apoptotic cell death [J].
Nicholson, DW .
CELL DEATH AND DIFFERENTIATION, 1999, 6 (11) :1028-1042
[34]   Activation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inula racemosa [J].
Pal, Harish Chandra ;
Sehar, Irum ;
Bhushan, Shashi ;
Gupta, Bishan Dutt ;
Saxena, Ajit Kumar .
TOXICOLOGY IN VITRO, 2010, 24 (06) :1599-1609
[35]   Mechanisms of cyclin-dependent kinase regulation: Structures of Cdks, their cyclin activators, and Cip and INK4 inhibitors [J].
Pavletich, NP .
JOURNAL OF MOLECULAR BIOLOGY, 1999, 287 (05) :821-828
[36]   Plant-derived anticancer agents [J].
Pezzuto, JM .
BIOCHEMICAL PHARMACOLOGY, 1997, 53 (02) :121-133
[37]  
Rasul A, 2011, ASIAN PAC J CANCER P, V12, P1219
[38]   Apoptosis-based therapies [J].
Reed, JC .
NATURE REVIEWS DRUG DISCOVERY, 2002, 1 (02) :111-121
[39]   New Role of (-)-Epicatechin in Enhancing the Induction of Growth Inhibition and Apoptosis in Human Lung Cancer Cells by Curcumin [J].
Saha, Achinto ;
Kuzuhara, Takashi ;
Echigo, Noriko ;
Suganuma, Masami ;
Fujiki, Hirota .
CANCER PREVENTION RESEARCH, 2010, 3 (08) :953-962
[40]   Tocotrienol-rich fraction of palm oil induces cell cycle arrest and apoptosis selectively in human prostate cancer cells [J].
Srivastava, Janmejai K. ;
Gupta, Sanjay .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 346 (02) :447-453