Periplocin inhibits growth of lung cancer in vitro and in vivo by blocking AKT/ERK signaling pathways.
Periplocin is one of cardenolides isolated from cortex periplocae which is used for treatment of rheumatoid arthritis and reinforcement of bones and tendons in traditional medicine. Here, we investigated the anti-tumor activity of periplocin against lung cancer cells bothin vitro and in vivo, and explored its anti-cancer mechanism. Periplocin inhibited the growth of lung cancer cells and induced their apoptosis in time- and dose-dependent manners by cell cycle arrest in G0/G1 phase. Periplocin exhibited anti-tumor activity both in human (A549) and mouse (LL/2) lung cancer xenograft models. Immunohistochemical analysis revealed that intratumoral angiogenesis was significantly suppressed. Furthermore, anti-cancer activity mediated by periplocin was associated with decreased level of phosphorylated AKT and ERK both in vitro and in vivo, which were important for cell growth and survival. Moreover, periplocin induced apoptosis by downregulating Bcl-2 and upregulating Bax, leading to activation of caspase-3 and caspase-9. These findings suggested that periplocin could inhibit the growth of lung cancer both in vitro and in vivo, which could be attributed to the inhibition of proliferation and the induction of apoptosis signaling pathway, such as AKT and ERK. These observations provide further evidence on the anti-tumor effect of periplocin, and it may be of importance to further explore its potential role as a therapeutic agent for cancer.
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China.
Ze J
ZJ
Lu
Yan
Y
Zhou
Qi
Q
Song
Zhao
Z
Qin
Hong
H
Zhang
Yong J
YJ
Zhou
Lan T
LT
Gou
Jin L
JL
Yang
Feng
F
Luo
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002470:Cell Survival; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016193:G1 Phase; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D012503:Saponins / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D014183:Transplantation, Heterologous; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D012503:Saponins; D051028:bcl-2-Associated X Protein; C502381:periplocin; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3; D053453:Caspase 9