title: A combination of pterostilbene with autophagy inhibitors exerts efficient apoptotic characteristics in both chemosensitive and chemoresistant lung cancer cells.
abstract: The emergence of multidrug resistance (MDR), meaning that cancer cells develop simultaneous resistance to different drugs, has limited the clinical efficacy and application of chemotherapy. Pterostilbene, a naturally occurring phytoalexin exerts a variety of pharmacologic activities, including cancer prevention, cytotoxicity, and antioxidant activity. In this study, results proved the capability of pterostilbene to effectively inhibit the cell viability of docetaxel-induced MDR human lung cancer cell lines through cell cycle arrest and apoptosis. Meanwhile, the observation of LC3-II production and formation of acidic vesicular organelles revealed an induction of autophagy at an early stage by pterostilbene, which was triggered by an inhibition of the AKT and JNK pathways and activation of ERK1/2. Furthermore, pretreatment with the autophagy inhibitors 3-methyladenine and bafilomycin A1 or with beclin-1 small interfering RNA was able to enhance pterostilbene-triggered apoptosis. In conclusion, this study demonstrated that pterostilbene causes autophagy and apoptosis in lung cancer cells. Furthermore, pterostilbene in combination with autophagy inhibitors may strengthen the efficiency of chemotherapeutic strategies in both chemosensitive and chemoresistant lung cancer cells, which may be of immense value for the clinical management of lung cancer patients with MDR.
authors.affiliation: * Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan, Republic of China;
authors.forename: Ming-Ju
authors.initials: MJ
authors.lastname: Hsieh
authors.forename: Chiao-Wen
authors.initials: CW
authors.lastname: Lin
authors.forename: Shun-Fa
authors.initials: SF
authors.lastname: Yang
authors.forename: Gwo-Tarng
authors.initials: GT
authors.lastname: Sheu
authors.forename: Ya-Yen
authors.initials: YY
authors.lastname: Yu
authors.forename: Mu-Kuan
authors.initials: MK
authors.lastname: Chen
authors.forename: Hui-Ling
authors.initials: HL
authors.lastname: Chiou
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018942:Macrolides / Q000494:pharmacology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology; D043823:Taxoids / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; C477012:MAP1LC3A protein, human; D018942:Macrolides; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D013267:Stilbenes; D043823:Taxoids; D000077143:Docetaxel; C107773:pterostilbene; C025946:3-methyladenine; C040929:bafilomycin A1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D000225:Adenine
keywords: apoptosis; autophagy.; multidrug resistance; pterostilbene