Deoxyarbutin displays antitumour activity against melanoma in vitro and in vivo through a p38-mediated mitochondria associated apoptotic pathway

脱氧熊果苷通过 p38 介导的线粒体相关凋亡途径在体外和体内表现出对黑色素瘤的抗肿瘤活性

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作者:Limei Ma, Yao Xu, Zeliang Wei, Guang Xin, Zhihua Xing, Hai Niu, Wen Huang

Abstract

Deoxyarbutin (DeoxyArbutin, dA), a natural compound widely used in skin lighting, displayed selectively cytotoxicity in vitro. In the study, we found that dA significantly inhibited viability/proliferation of B16F10 melanoma cells, induced tumour cell arrest and apoptosis. Furthermore, dA triggered its pro-apoptosis through damaging the mitochondrial function (membrane potential loss, ATP depletion and ROS overload generation etc.) and activating caspase-9, PARP, caspase-3 and the phosphorylation of p38. Treatment with p38 agonist confirmed the involvement of p38 pathway triggered by dA in B16F10 cells. The in vivo finding also revealed that administration of dA significantly decreased the tumour volume and tumour metastasis in B16F10 xenograft model by inhibiting tumour proliferation and inducing tumour apoptosis. Importantly, the results indicated that dA was specific against tumour cell lines and had no observed systemic toxicity in vivo. Taken together, our study demonstrated that dA could combate tumour in vitro and in vivo by inhibiting the proliferation and metastasis of tumour via a p38-mediated mitochondria associated apoptotic pathway.

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