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Selenocysteine derivative overcomes TRAIL resistance in melanoma cells: evidence for ROS-dependent synergism and signaling crosstalk.

ABSTRACT: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as one of the most promising targeted drug for new cancer therapeutics, is limited in clinical application by the evolution of resistance in many cancer cell lines, especially in malignant melanoma. Thus, it is urgently needed to identify chemosensitizers to enhance the apoptotic inducing ef?cacy of TRAIL and overcome resistance of malignant melanoma cells. Herein, we reported that 3,3'-diselenodipropionic acid (DSeA), a Selenocysteine derivative, could synergistically enhance the growth inhibitory effect of TRAIL on A375 melanoma cells though induction of ROS-dependent apoptosis with involvement of PTEN-mediated Akt inactivation and DNA damage-mediated p53 phosphorylation, which subsequently activated mitochondrial and death receptor apoptotic pathways. Moreover, silencing of p53 down-regulated the expression levels of p53-inducible genes, and effectively blocked the cell apoptosis. Suppression of PI3K signi?cantly increased the apoptotic cell death. In contrast, antioxidants effectively reversed the cell apoptosis through regulation of Akt and p53 signaling pathways. Taken together, the combination of DSeA and TRAIL could be a novel strategy to overcome TRAIL resistance in malignant melanoma, and DSeA may be candidates for further evaluation as a chemosensitizer in clinical trails.

SUBMITTER: Cao W

PROVIDER: S-EPMC4202134 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Selenocysteine derivative overcomes TRAIL resistance in melanoma cells: evidence for ROS-dependent synergism and signaling crosstalk.

Cao Wenqiang W Li Xiaoling X Zheng Shanyuan S Zheng Wenjie W Wong Yum-Shing YS Chen Tianfeng T

Oncotarget 20140901 17

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), as one of the most promising targeted drug for new cancer therapeutics, is limited in clinical application by the evolution of resistance in many cancer cell lines, especially in malignant melanoma. Thus, it is urgently needed to identify chemosensitizers to enhance the apoptotic inducing efﬁcacy of TRAIL and overcome resistance of malignant melanoma cells. Herein, we reported that 3,3'-diselenodipropionic acid (DSeA), a Selenocyst ...[more]

PMID: 25277183

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Dataset Information

Selenocysteine derivative overcomes TRAIL resistance in melanoma cells: evidence for ROS-dependent synergism and signaling crosstalk.

Publications

Selenocysteine derivative overcomes TRAIL resistance in melanoma cells: evidence for ROS-dependent synergism and signaling crosstalk.

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