Role of p38 MAPK activation and mitochondrial cytochrome-c release in allicin-induced apoptosis in SK-N-SH cells

被引:29
作者
Zhuang, Jianhui [1 ]
Li, Yu [2 ]
Chi, Yufen [3 ]
机构
[1] Peoples Hosp Rizhao, Dept Urinary Surg, Rizhao 276826, Shandong, Peoples R China
[2] Peoples Hosp Rizhao, Dept Obstet & Gynaecol, Rizhao 276826, Shandong, Peoples R China
[3] Peoples Hosp Rizhao, Dept Paediat, Rizhao 276826, Shandong, Peoples R China
关键词
cytochrome-c; allicin; p38; MAPK; neuroblastoma; apoptosis; CANCER CELLS; DEATH; LINE; REQUIREMENT; AUTOPHAGY; SGC-7901; GROWTH;
D O I
10.1097/CAD.0000000000000340
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Here, we investigate the apoptotic effect of allicin, the predominant component of freshly crushed garlic, on neuroblastoma cells. In this paper, the authors have first assessed the effect of allicin on human neuroblastoma SK-N-SH cells and then investigated the underlying mechanism. The results indicate that allicin suppresses SK-N-SH cell growth in a dose-dependent and time-dependent manner and that 5 mu mol/l of allicin leads to a significant increase in apoptotic rate with annexin-V/PI double staining. Western blot analysis shows that treatment with allicin-induced apoptosis through activation of caspases-3 and 9. Phosphorylation of p38 MAPK contributes to allicin-induced apoptosis upstream of caspase activation. Using p38 MAPK inhibitor, the authors discovered that p38 MAPK activation subsequently induces the release of cytochrome-c from mitochondria into the cytosol. Taken together, the results demonstrate that allicin can activate the p38 MAPK pathway, which leads to mitochondrial release of cytochrome-c, thus inducing SK-N-SH cell apoptosis. Overall, this study suggests that allicin may be used as one of the novel pharmacological treatment strategies in neuroblastoma.
引用
收藏
页码:312 / 317
页数:6
相关论文
共 45 条
[21]   How cell death shapes cancer [J].
Labi, V. ;
Erlacher, M. .
CELL DEATH & DISEASE, 2015, 6 :e1675-e1675
[22]   Allicin Alleviates Inflammation of Trinitrobenzenesulfonic Acid-Induced Rats and Suppresses P38 and JNK Pathways in Caco-2 Cells [J].
Li, Chen ;
Lun, Weijian ;
Zhao, Xinmei ;
Lei, Shan ;
Guo, Yandong ;
Ma, Jiayi ;
Zhi, Fachao .
MEDIATORS OF INFLAMMATION, 2015, 2015
[23]   A small molecule, MTBT, prevents cancer cell growth by activating p38 MAPK [J].
Li, Yan ;
Zhang, Xuelian ;
Zhang, Jing ;
Li, Yongzhen ;
Liu, Wei ;
Wang, Zhen ;
Wang, Yanchang ;
Si, Shuyi .
ANTI-CANCER DRUGS, 2014, 25 (04) :423-432
[24]   Induction of apoptotic program in cell-free extracts: Requirement for dATP and cytochrome c [J].
Liu, XS ;
Kim, CN ;
Yang, J ;
Jemmerson, R ;
Wang, XD .
CELL, 1996, 86 (01) :147-157
[25]   Self-eating and self-killing: crosstalk between autophagy and apoptosis [J].
Maiuri, M. Chiara ;
Zalckvar, Einat ;
Kimchi, Adi ;
Kroemer, Guido .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2007, 8 (09) :741-752
[26]   Neuroblastoma [J].
Maris, John M. ;
Hogarty, Michael D. ;
Bagatell, Rochelle ;
Cohn, Susan L. .
LANCET, 2007, 369 (9579) :2106-2120
[27]   Requirement of cytochrome c for apoptosis in human cells [J].
Matapurkar, A. ;
Lazebnik, Y. .
CELL DEATH AND DIFFERENTIATION, 2006, 13 (12) :2062-2067
[28]   Alliin is a suicide substrate of Citrobacter freundii methionine γ-lyase: structural bases of inactivation of the enzyme [J].
Morozova, Elena A. ;
Revtovich, Svetlana V. ;
Anufrieva, Natalya V. ;
Kulikova, Vitalia V. ;
Nikulin, Alexey D. ;
Demidkina, Tatyana V. .
ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2014, 70 :3034-3042
[29]   Allicin (from garlic) induces caspase-mediated apoptosis in cancer cells [J].
Oommen, S ;
Anto, RJ ;
Srinivas, G ;
Karunagaran, D .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 485 (1-3) :97-103
[30]  
Orekhov Alexander N, 2013, Recent Pat Cardiovasc Drug Discov, V8, P56