Antitumor effects of arsenic disulfide on the viability, migratory ability, apoptosis and autophagy of breast cancer cells.
Antitumor effects of arsenic disulfide on the viability, migratory ability, apoptosis and autophagy of breast cancer cells.
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DOI：
10.3892/or.2018.6780
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发表时间：
2019-01
期刊：
影响因子：
4.2
通讯作者：
Hirano T
中科院分区：
文献类型：
--
作者：
Zhao Y;Onda K;Sugiyama K;Yuan B;Tanaka S;Takagi N;Hirano T
本研究研究了二硫化砷（As2S2）对人乳腺癌MCF-7和MDA-MB-231细胞增殖、存活和迁移能力的影响，并探讨了其潜在的分子机制，重点探讨了其在细胞周期阻滞、诱导凋亡、诱导自噬和活性氧（ROS）生成等方面的作用。结果表明，As2S2显著抑制乳腺癌细胞的活力、存活和迁移，并呈剂量依赖性。此外，我们发现As2S2通过调节相关蛋白的表达，包括细胞周期蛋白B1和细胞分裂周期蛋白2，在两种乳腺癌细胞系中主要诱导细胞周期阻滞在G2/M期。除了细胞周期阻滞外，As2S2还通过激活促凋亡蛋白caspase-7和- 8的表达，以及增加b细胞淋巴瘤2 （Bcl-2）相关的X蛋白/Bcl-2比值，同时降低抗凋亡b细胞淋巴瘤超大蛋白的表达，从而触发细胞凋亡的诱导。此外，As2S2刺激了微管相关蛋白1A/ 1b -轻链3 (LC3)-II的积累，增加了LC3-II/LC3- i的比值，表明发生了自噬。As2S2处理还能抑制基质金属蛋白酶-9 （matrix metalloproteinase-9, MMP-9）蛋白的表达，但增加了两种乳腺癌细胞系细胞内ROS的积累，这可能有助于减轻乳腺癌的转移和减缓乳腺癌的进展。综上所述，本研究结果表明，As2S2通过调控细胞周期阻滞、内源性和外源性凋亡、自噬、MMP-9信号传导和ROS生成，抑制人乳腺癌细胞的进展。
In the present study, the antitumor effects of arsenic disulfide (As2S2) on the proliferative, survival and migratory ability of human breast cancer MCF-7 and MDA-MB-231 cells were investigated, and its potential underlying molecular mechanisms with an emphasis on cell cycle arrest, apoptosis induction, autophagy induction and reactive oxygen species (ROS) generation were determined. The results indicated that As2S2 significantly inhibited the viability, survival and migration of breast cancer cells in a dose-dependent manner. In addition, it was identified that As2S2 induced cell cycle arrest primarily at G2/M phase in the two breast cancer cell lines by regulating the expression of associated proteins, including cyclin B1 and cell division cycle protein 2. In addition to cell cycle arrest, As2S2 also triggered the induction of apoptosis in cells by activating the expression of pro-apoptotic proteins, including caspase-7 and −8, as well as increasing the B-cell lymphoma 2 (Bcl-2)-associated X protein/Bcl-2 ratio, while decreasing the protein expression of anti-apoptotic B-cell lymphoma extra-large. In addition, As2S2 stimulated the accumulation of microtubule-associated protein 1A/1B-light chain 3 (LC3)-II and increased the LC3-II/LC3-I ratio, indicating the occurrence of autophagy. As2S2 treatment also inhibited the protein expression of matrix metalloproteinase-9 (MMP-9), but increased the intracellular accumulation of ROS in the two breast cancer cell lines, which may assist in alleviating metastasis and attenuating the progression of breast cancer. Taken together, the results of the present study suggest that As2S2 inhibits the progression of human breast cancer cells through the regulation of cell cycle arrest, intrinsic and extrinsic apoptosis, autophagy, MMP-9 signaling and ROS generation.
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