Autophagy inhibition promotes paclitaxel-induced apoptosis in cancer cells

• Published in: Cancer letters Vol. 307; no. 2; pp. 141 - 148
• Main Authors: Xi, Guangmin, Hu, Xiaoyan, Wu, Baolin, Jiang, Hanming, Young, Charles Y.F, Pang, Yingxin, Yuan, Huiqing
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 28-08-2011; Elsevier Limited
• Subjects: Antibiotics; Antineoplastic Agents, Phytogenic - pharmacology; Apoptosis; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Blotting, Western; Cancer; Cancer therapies; Cell Line, Tumor; Chemotherapy; Cytotoxicity; genes; green fluorescent protein; Hematology, Oncology and Palliative Medicine; Humans; Lung cancer; organelles; Paclitaxel; Paclitaxel - pharmacology; Proteins; RNA Interference; RNA, Small Interfering; small interfering RNA; microtubule-associated protein 1 light chain 3; Lung cancer; AVOs; Paclitaxel; 3-MA; MTT; acidic vesicular organelles; LC3; Autophagy; 3-methyladenine; 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazoliumbromide; Apoptosis
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2011.03.026

Abstract Paclitaxel has been demonstrated to be an effective mitotic inhibitor and apoptosis inducer to treat aggressive malignancies. In this paper, we have provided a line of evidence that promotion of apoptotic cell death by paclitaxel was accompanied with induction of autophagy in A549 cells. Paclitaxel treatment could lead to the formation of acidic vesicular organelles (AVOs), the induction of Atg5, Beclin 1 and microtubule-associated protein 1 light chain 3 (LC3) expressions, and the increase of punctate fluorescent signals in A549 cells pre-transfected with green fluorescent protein (GFP)-tagged LC3. Interestingly, paclitaxel-mediated apoptotic cell death was further potentiated by pretreatment with autophagy inhibitor 3-methyladenine (3-MA) or small interfering RNA against the autophagic gene beclin 1 . These findings suggest that paclitaxel-elicited autophagic response plays a protective role that impedes the eventual cell death, and inhibition of autophagy could be an adjunctive strategy for enhancing chemotherapeutic effect of paclitaxel as an antitumor agent.