title: Apoptotic Effect of Galbanic Acid via Activation of Caspases and Inhibition of Mcl-1 in H460 Non-Small Lung Carcinoma Cells.
abstract: Galbanic acid (GBA), a major compound of Ferula assafoetida, was known to have cytotoxic, anti-angiogenic and apoptotic effects in prostate cancer and murine Lewis lung cancer cells; the underling apoptotic mechanism of GBA still remains unclear so far. Thus, in the present study, the apoptotic mechanism of GBA was investigated mainly in H460 non-small cell lung carcinoma (NSCLC) cells because H460 cells were most susceptible to GBA than A549, PC-9 and HCC827 NSCLC cells. Galbanic acid showed cytotoxicity in wild EGFR type H460 and A549 cells better than other mutant type PC-9 and HCC827 NSCLC cells. Also, GBA significantly increased the number of Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells and sub G1 population in H460 cells. Western blotting revealed that GBA cleaved poly (ADP-ribose) polymerase (PARP), activated Bax and caspase 9, attenuated the expression of Bcl-2, Bcl-x(L), and Myeloid cell leukemia 1 (Mcl-1) in H460 cells. However, interestingly, overexpression of Mcl-1 blocked the ability of GBA to exert cytotoxicity, activate caspase9 and Bax, cleave PARP, and increase sub G1 accumulation in H460 cells. Overall, these findings suggest that GBA induces apoptosis in H460 cells via caspase activation and Mcl-1 inhibition in H460 cells as a potent anticancer agent for NSCLC treatment.
authors.affiliation: College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, Korea.
authors.forename: Bum-Seok
authors.initials: BS
authors.lastname: Oh
authors.affiliation: College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, Korea.
authors.forename: Eun Ah
authors.initials: EA
authors.lastname: Shin
authors.affiliation: College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, Korea.
authors.forename: Ji Hoon
authors.initials: JH
authors.lastname: Jung
authors.affiliation: College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, Korea.
authors.forename: Deok-Beom
authors.initials: DB
authors.lastname: Jung
authors.affiliation: College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, Korea.
authors.forename: Bonglee
authors.initials: B
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, Korea.
authors.forename: Bum Sang
authors.initials: BS
authors.lastname: Shim
authors.affiliation: Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashad, Iran.
authors.forename: Mahsa Chitsazian
authors.initials: MC
authors.lastname: Yazdi
authors.affiliation: Biotechnology Research Center and School of Pharmacy, Mashhad University of Medical Sciences, Mashad, Iran.
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Iranshahi
authors.affiliation: College of Korean Medicine, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul, 131-701, Korea.
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D045744:Cell Line, Tumor / Q000187:drug effects; D003374:Coumarins / Q000494:pharmacology*; D005309:Ferula / Q000737:chemistry; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D003374:Coumarins; C579095:MCL1 protein, human; D064549:Myeloid Cell Leukemia Sequence 1 Protein; C048972:galbanic acid; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases
keywords: Galbanic acid; Mcl-1; TGF β1; caspase9/3; lung cancer; sub G1