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Effects of alpha-lipoic acid on chemotherapy and detachment-induced cell death in human non-small cell lung cancer H460 cells |
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| รหัสดีโอไอ | |
| Title | Effects of alpha-lipoic acid on chemotherapy and detachment-induced cell death in human non-small cell lung cancer H460 cells |
| Creator | Punyawee Puchsaka |
| Contributor | Pithi Chanvorachote, Chatchai Chaotham |
| Publisher | Chulalongkorn University |
| Publication Year | 2558 |
| Keyword | Cancer cells, Lungs -- Cancer, Cancer -- Chemotherapy, เซลล์มะเร็ง, ปอด -- มะเร็ง, มะเร็ง -- เคมีบำบัด |
| Abstract | Chemotherapeutic failure and metastasis are the main causes of high mortality rate in lung cancer. Alteration of cellular redox status in response to endogenous stimuli or exogenous compounds has a significant impact on cell signaling and behavior. Herein we divulge for the first time that lung cancer cells exposed to alpha-lipoic acid (LA) resulted in a higher level of cellular hydrogen peroxide (H2O2) and superoxide anion (O2·-) , and such an increase of the specific reactive oxygen species (ROS) downregulated integrin β1 and β3, the integrins known for potentiating aggressive behaviors and metastasis. The LA-treated cells exhibited significant decrease in their abilities to survive in detached condition or anoikis resistance and grow in anchorage-independent soft agar assay. Furthermore, LA sensitized the cells to cisplatin, etoposide and paclitaxel-induced apoptosis. For underlying mechanism, we found that the treatment of the cells with LA significantly decreased integrin β1 and β3, while had no effect on integrin α5 and αv. Interestingly, survival protein p-AKT and anti-apoptotic protein Bcl-2 were reduced in an association to such integrin modulations. Using ROS probes and selective anti-oxidants, we have proved that H2O2 and O2·- induced by LA are key players for the decrease of β1 and β3 integrins, respectively. These findings indicate a novel effect of LA as well as specific ROS, O2·- and H2O2 in integrin regulation, anoikis and chemotherapeutic sensitizations. |
| URL Website | cuir.car.chula.ac.th |
