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

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.

SUBMITTER: Ma L

PROVIDER: S-EPMC5543205 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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

Ma Limei L Xu Yao Y Wei Zeliang Z Xin Guang G Xing Zhihua Z Niu Hai H Huang Wen W

Scientific reports 20170803 1

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 phosphorylatio ...[more]

PMID: 28775302

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Project description:The efficacy of available treatments for melanoma is limited by side effects and the rapidly emerging resistance to treatment. In this context, the decavanadate compounds represent promising tools to design efficient therapeutic agents. In our study, we synthesized a dimagnesium disodium decavanadate icosahydrate compound (Mg2Na2V10O28·20H2O) and investigated its structure stability as well as its antimelanoma effects. Results showed that the Mg2Na2V10O28·20H2O compound is structured in a monoclinic system with the space group C2/c, stabilized by oxygen vertices, hydrogen bonds, and van der Waals interactions. Interestingly, we found that this newly synthesized compound reduced the viability of human (IGR39, IGR37, and SKMEL28) and murine (B16-F10) melanoma cells in a dose-dependent manner. The IC50 values ranged from 7.3 to 18 μM after 24 h and decreased to 1.4 μM after 72 h of treatment. Notably, this effect was more important than that of cisplatin (IC50 = 3 μM after 72 h of treatment), a chemotherapeutic agent, commonly used in the treatment of malignant melanoma. Furthermore, the cytotoxicity of the decavanadate compound was relatively weak on normal human keratinocytes (HaCaT), with a light effect (IC50 >> 70 μM) observed after 24 h of treatment. Thus, the Mg2Na2V10O28·20H2O compound displayed an advantage over cisplatin, which was reported to be much more aggressive to the keratinocyte cell line (IC50 = 23.9 μM). Moreover, it inhibited dose-dependently the adhesion of IGR39 cells to collagen (IC50 = 2.67 μM) and fibronectin, as well as their migration with an IC50 value of 2.23 μM. More interestingly, its in vivo administration to B16-F10 allografted mice, at the nontoxic dose of 50 μg (2.5 mg/kg), prevented and suppressed by 70% the tumor growth, compared to the nontreated mice. Moreover, this compound has also allowed a recovery against inflammation induced in mice by a mixture of DMBA and croton oil. Thus, all our results showed the potential of the Mg2Na2V10O28·20H2O compound to prevent and efficiently treat the growth and metastasis of melanoma.

Dataset Information

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

Publications

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

Similar Datasets

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