Apisara Ausawasamrit1, Nattawut Itthiwarapornkul1, Chatchai Chaotham2, Suchada Sukrong3, Pithi Chanvorachote4. 1. Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. 2. Department of Biochemistry and Microbiology, Chulalongkorn University, Bangkok, Thailand Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand. 3. Department of Pharmacognosy and Pharmaceutical Botany, Chulalongkorn University, Bangkok, Thailand Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand pithi_chan@yahoo.com Suchada.su@chula.ac.th. 4. Department of Pharmacology and Physiology, Chulalongkorn University, Bangkok, Thailand Cell-Based Drug and Health Product Development Research Unit, Chulalongkorn University, Bangkok, Thailand Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand pithi_chan@yahoo.com Suchada.su@chula.ac.th.
Abstract
BACKGROUND/AIM: The ability of cancer cells to resist to anoikis has been shown to augment cancer cell metastasis in many cancers. In search for potential substances for anti-metastatic approaches, this study aimed to investigate anoikis-sensitizing activity of lupalbigenin, extracted from Derris scandens. MATERIALS AND METHODS: Human lung cancer cells were treated with non-cytotoxic concentrations of lupalbigenin in a detachment condition. Anoikis was evaluated at various time points using MTT viability assays. The effect of lupalbigenin on anchorage-independent growth was performed by soft-agar assay. The survival signaling proteins, as well as regulatory proteins of apoptosis and metastasis, were examined by western blot analysis. RESULTS: Lupalbigenin treatment significantly down-regulated survival proteins, including protein kinase B (pAKT/AKT) and extracellular signal-regulated kinase (pERK/ERK), as well as anti-apoptotic protein B-cell lymphoma 2 (BCL-2), resulting in the enhancement of the cellular response to anoikis and the decrease of growth and survival in an anchorage-independent condition. CONCLUSION: Lupalbigenin sensitizes detachment-induced cell death in human lung cancer cell through down-regulation of pro-survival proteins. Copyright
BACKGROUND/AIM: The ability of cancer cells to resist to anoikis has been shown to augment cancer cell metastasis in many cancers. In search for potential substances for anti-metastatic approaches, this study aimed to investigate anoikis-sensitizing activity of lupalbigenin, extracted from Derris scandens. MATERIALS AND METHODS:Humanlung cancer cells were treated with non-cytotoxic concentrations of lupalbigenin in a detachment condition. Anoikis was evaluated at various time points using MTT viability assays. The effect of lupalbigenin on anchorage-independent growth was performed by soft-agar assay. The survival signaling proteins, as well as regulatory proteins of apoptosis and metastasis, were examined by western blot analysis. RESULTS:Lupalbigenin treatment significantly down-regulated survival proteins, including protein kinase B (pAKT/AKT) and extracellular signal-regulated kinase (pERK/ERK), as well as anti-apoptotic protein B-cell lymphoma 2 (BCL-2), resulting in the enhancement of the cellular response to anoikis and the decrease of growth and survival in an anchorage-independent condition. CONCLUSION:Lupalbigenin sensitizes detachment-induced cell death in human lung cancer cell through down-regulation of pro-survival proteins. Copyright