title: Piperlongumine induces apoptosis and autophagy in human lung cancer cells through inhibition of PI3K/Akt/mTOR pathway.
abstract: Piperlongumine (PL), a natural alkaloid present in the fruit of the Long pepper, is known to exhibit notable anti-cancer effects. Nonetheless, the anti-tumor effect of PL in lung cancer cells still remains unclear. In the present study, we reported the chemotherapeutic effects of PL using in vitro and in vivo models. We showed that PL displayed potent anti-neoplastic activity against lung cancer A549 cells as well as corresponding docetaxel-resistant A549/DTX cells. In addition, we found that PL induced apoptosis in both A549 and A549/DTX cells. PL also induced autophagy in A549/DTX cells. Moreover, autophagy-specific inhibitors (3-methyladenine) or Beclin1 and Atg 5 small interfering RNAs (siRNAs) enhanced PL-induced apoptosis, indicating that PL-mediated autophagy may protect A549/DTX cells from undergoing apoptotic cell death. Furthermore, we observed the inhibition of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway by PL. Finally, PL inhibited the growth of A549/DTX xenograft tumors, which was associated with inhibition of cell proliferation, induction of apoptosis of tumor cells and decreased expression of p-Akt and p-mTOR in tumor xenograft tissues. In summary, our study demonstrated that PL induced apoptosis and autophagy through modulation of the PI3K/Akt/mTOR pathway in human lung cancer cells. This study may provide a rationale for future clinical application using PL as a chemotherapeutic agent for lung cancer.
authors.affiliation: Department of Cardiothoracic Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Oncology Center, Affiliated Hospital of Jiangnan University, Wuxi, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Cardiothoracic Surgery, Affiliated Hospital of Jiangnan University, Wuxi, PR China wxsytsg@126.com.
authors.forename: Qingjun
authors.initials: Q
authors.lastname: You
authors.affiliation: Oncology Center, Affiliated Hospital of Jiangnan University, Wuxi, PR China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Oncology Center, Affiliated Hospital of Jiangnan University, Wuxi, PR China.
authors.forename: Dongyan
authors.initials: D
authors.lastname: Cai
mesh_terms: D000072283:A549 Cells; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004148:Dioxolanes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D010881:Piperidones
chemical_list: D000225:Adenine; D000970:Antineoplastic Agents; D004148:Dioxolanes; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D058570:TOR Serine-Threonine Kinases; C025946:3-methyladenine; C546842:MTOR protein, human; C498077:piperlongumine; D010881:Piperidones
keywords: PI3K/Akt/mTOR pathway; apoptosis; autophagy; lung cancer; piperlongumine