4 results on '"Shikun Zhou"'
Search Results
2. Tubeimoside I-induced lung cancer cell death and the underlying crosstalk between lysosomes and mitochondria
- Author
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Yujuan Zhan, Kun Wang, Bonan Chen, Yuhua Lu, Shikun Zhou, Biaoyan Du, Xianli Wei, Jianyong Xiao, Xiaodong Liu, Weibin Zhang, and Ting Yin
- Subjects
Male ,0301 basic medicine ,China ,Cancer Research ,Lung Neoplasms ,Immunology ,Mice, Nude ,Apoptosis ,Mitochondrion ,Permeability ,Article ,Cathepsin B ,Mice ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,0302 clinical medicine ,Downregulation and upregulation ,Cell Line, Tumor ,Autophagy ,Animals ,Humans ,Medicine, Chinese Traditional ,lcsh:QH573-671 ,bcl-2-Associated X Protein ,Membrane Potential, Mitochondrial ,Cathepsin ,Mice, Inbred BALB C ,Drug discovery ,lcsh:Cytology ,Chemistry ,Cell Biology ,Saponins ,Triterpenes ,Mitochondria ,Cell biology ,Cytosol ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cancer cell ,Lung cancer ,Lysosomes ,Reactive Oxygen Species - Abstract
Cancer cells have developed chemoresistance and have improved their survival through the upregulation of autophagic mechanisms that protect mitochondrial function. Here, we report that the traditional Chinese anticancer agent tubeimoside I (Tub), which is a potent inhibitor of autophagy, can promote mitochondria-associated apoptosis in lung cancer cells. We found that Tub disrupted both mitochondrial and lysosomal pathways. One of its mechanisms was the induction of DRP1-mediated mitochondrial fragmentation. Another mechanism was the blocking of late-stage autophagic flux via impairment of lysosomal acidification through V-ATPase inhibition; this blocks the removal of dysfunctional mitochondria and results in reactive oxygen species (ROS) accumulation. Excessive ROS accumulation causes damage to lysosomal membranes and increases lysosomal membrane permeability, which leads to the leakage of cathepsin B. Finally, cathepsin B upregulates Bax-mediated mitochondrial outer membrane permeability and, subsequently, cytosolic cytochrome C-mediated caspase-dependent apoptosis. Thus, the cancer cell killing effect of Tub is enhanced through the formation of a positive feedback loop. The killing effect of Tub on lung cancer cells was verified in xenografted mice. In summary, Tub exerts a dual anticancer effect that involves the disruption of mitochondrial and lysosomal pathways and their interaction and, thereby, has a specific and enhanced killing effect on lung cancer cells.
- Published
- 2020
3. Dioscin Inhibits the Invasion and Migration of Hepatocellular Carcinoma HepG2 Cells by Reversing TGF-β1-Induced Epithelial-Mesenchymal Transition
- Author
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Liang Qiqi, Kun Wang, Xianli Wei, Weizhen Ao, Junzi Ke, Yujuan Zhan, Jianyong Xiao, Pingping Zhu, Yu Hou, Bonan Chen, and Shikun Zhou
- Subjects
MAPK/ERK pathway ,p38 mitogen-activated protein kinases ,epithelial-mesenchymal transition ,Pharmaceutical Science ,Vimentin ,Diosgenin ,p38 Mitogen-Activated Protein Kinases ,Article ,Analytical Chemistry ,Transforming Growth Factor beta1 ,lcsh:QD241-441 ,03 medical and health sciences ,0302 clinical medicine ,lcsh:Organic chemistry ,Cell Movement ,TGF-β1 ,Drug Discovery ,dioscin ,Humans ,Neoplasm Invasiveness ,Epithelial–mesenchymal transition ,Physical and Theoretical Chemistry ,Cell Proliferation ,030304 developmental biology ,0303 health sciences ,biology ,Activator (genetics) ,Chemistry ,Kinase ,Liver Neoplasms ,Organic Chemistry ,Mesenchymal stem cell ,Hep G2 Cells ,MAPK ,hepatocellular carcinoma cells ,Gene Expression Regulation, Neoplastic ,Chemistry (miscellaneous) ,030220 oncology & carcinogenesis ,Cancer research ,biology.protein ,Molecular Medicine ,Pentacyclic Triterpenes ,Signal Transduction ,Transforming growth factor - Abstract
Dioscin is a natural steroidal saponin that can be isolated from Chinese medicine, such as Dioscoreae rhizoma. It has wild range of pharmacological activities such as hepatoprotection, a lipid-lowering effect, and anti-inflammation. Recently, mounting studies reported the anticancer effect of dioscin on a variety of tumor cells. However, the potential effect of dioscin on the epithelial-mesenchymal transition (EMT) of HepG2 cells is unclear. In the present study, dioscin was identified to inhibit transforming growth factor-&beta, 1 (TGF-&beta, 1) and induced invasive and migratory behavior of HepG2 cells. Consistently, the expression of the epithelial marker E-cadherin and gap junction proteins increased following dioscin treatment, while mesenchymal markers decreased, including N-cadherin, Vimentin, Snail, and Slug. Furthermore, we discovered that TGF-&beta, 1 induces phosphorylation of JNK, p38, and Erk, whereas the activation of these kinases was reversed by dioscin treatment in a dose-dependent manner. With the addition of Asiatic acid, a p38 activator, the inhibitory effect of dioscin on EMT was reversed. Taken together, these data indicated that dioscin inhibits EMT in HepG2 cells, which is mediated in large part by inhibition of the p38-MAPK signaling.
- Published
- 2019
4. N-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells
- Author
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Yujuan Zhan, Hiuting Idy Ho, Xiaodong Liu, Ting Yin, Yuhua Lu, Weijie Wu, Jiawei Chen, Yuhui Tan, Yilin Zhang, Wenli Mao, Jianyong Xiao, Biaoyan Du, Kun Wang, Bonan Chen, and Shikun Zhou
- Subjects
MAPK/ERK pathway ,p38 mitogen-activated protein kinases ,NSCLC ,Article ,Catalysis ,lcsh:Chemistry ,Inorganic Chemistry ,Physical and Theoretical Chemistry ,Protein kinase A ,lcsh:QH301-705.5 ,Molecular Biology ,Spectroscopy ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,Chemistry ,Kinase ,Organic Chemistry ,Autophagy ,autophagy inhibition ,apoptosis ,ROS ,General Medicine ,N-Methylparoxetine ,MAPK ,Computer Science Applications ,lcsh:Biology (General) ,lcsh:QD1-999 ,Apoptosis ,Mitogen-activated protein kinase ,Cancer research ,biology.protein - Abstract
The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified N-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions&mdash, mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells.
- Published
- 2019
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