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

Abstract

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 μmol/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.

Cost Effective Use of a Thiosulfinate-Enriched Allium sativum Extract in Combination with Chemotherapy in Colon Cancer

“…Research has revealed that allicin targets multiple pathways implied in the inhibition of cancer development [27], including cell cycle arrest [21,28], the induction of apoptosis [29][30][31][32][33][34], the induction of histone acetylation [35] and the inhibition of angiogenesis [36]. Some of these studies dealing with the induction of apoptosis by allicin have also been reported for Caco-2 and HT-29 [20,34,37].…”

Curcumin analog EF24 induces apoptosis and downregulates the mitogen activated protein kinase/extracellular signal-regulated signaling pathway in oral squamous cell carcinoma

“…Various cytotoxic agents induce apoptotic cell death via deactivation of MAPK signaling and induction of caspase-3 and -9 (31). In addition, the MAPK signaling pathway triggers the release of intermediate proteins in apoptosis, including cytochrome c, in cancer cells (32). Liu et al (33) reported that release of cytochrome c from the mitochondria was increased in the EF24-treated group.…”

Dual-Specificity Phosphatases in Neuroblastoma Cell Growth and Differentiation

“…The influence of alterations in JNK and p38 MAPK pathways in NB cell growth has been investigated less. Higher sensitivity to apoptotic stimuli has mainly been reported in NB cell lines upon pharmacological inhibition of JNKs or p38s, although an anti-apoptotic outcome after inhibition of these MAPKs has also been reported [55,56,57,58,59] (Table 1). A complex scenario emerges in NB in which the specific contribution of the effectors from the distinct MAPK pathways may differentially drive NB cell growth, differentiation, and apoptosis, with variable consequences in the response to chemotherapies.…”