A new semisynthetic 1-O-acetyl-6-O-lauroylbritannilactone induces apoptosis of human laryngocarcinoma cells through p53-dependent pathway.
Initiation of apoptosis is an important event for chemoprevention and chemotherapy of cancer. Naturally derived products had drawn growing attention as lead compounds for anticancer drug discovery. ABL-L, a semisynthetic analogue of natural sesquiterpenoid 1-O-acetylbritannilactone (ABL) isolated from Inula britannica, showed stronger suppression against three solid tumor cell lines with 4-10 fold improvement than ABL. However, its molecular mechanism of cell death induction has still not been determined. The present study evaluated the anticancer efficacy of ABL-L and its biological activities mechanism on human laryngocarcinoma cells HEp-2 in vitro. We found that ABL-L-induced inhibition of cell proliferation was associated with an increase in G1-phase arrest. Typical apoptotic morphological and biochemical features were also observed in treated cells. Furthermore, the levels of the anti-apoptotic Bcl-2, pro-caspase 3/8/9 and poly(ADP-ribose) polymerase PARP decreased, and the level of pro-apoptotic Bax increased. Involvement of the caspase-mediated apoptosis was confirmed using caspase inhibitor Z-VAD-FMK pretreatment. In addition, ABL-L induced a tumor suppressor p53 and its target genes expression p21, fas, noxa and puma. The results of p53 knockdown suggest that caspase-mediated apoptosis induced by ABL-L was in p53-dependent pathway on HEp-2 cells. Our data indicate that the cytotoxicity of the novel semisynthetic analogue ABL-L involved G1 cell cycle arrest and apoptosis via a p53-dependent, caspase-mediated pathway on human laryngocarcinoma cells.
College of Life Sciences, Northwest A&F University, Yangling 712100, China.
Yang-Yang
YY
Han
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, China. Electronic address: tangjiang11@nwsuaf.edu.cn.
Jiang-Jiang
JJ
Tang
College of Life Sciences, Northwest A&F University, Yangling 712100, China.
Rong-Fang
RF
Gao
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, China.
Xin
X
Guo
College of Life Sciences, Northwest A&F University, Yangling 712100, China; Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China. Electronic address: leiming70@hotmail.com.
Ming
M
Lei
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, China.
Jin-Ming
JM
Gao
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D006801:Humans; D007783:Lactones / Q000494:pharmacology*; D007822:Laryngeal Neoplasms; D012717:Sesquiterpenes / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
C000616457:1-O-acetyl-6-O-lauroylbritannilactone; D000970:Antineoplastic Agents; D007783:Lactones; D012717:Sesquiterpenes; D016159:Tumor Suppressor Protein p53
Apoptosis; Britannilactone; Cell cycle arrest; Laryngocarcinoma; p53