13-Methyltetradecanoic acid induces mitochondrial-mediated apoptosis in human bladder cancer cells.
OBJECTIVE
13-Methyltetradecanoic acid (13-MTD), a saturated branched-chain fatty acid purified from soy fermentation products, is known to induce apoptosis in many types of human cancer cells. This study was designed to investigate the molecular mechanisms involved in 13-MTD-induced apoptosis in human bladder cancer cells.


METHODS
MTT assay was used to investigate the potential effects of 13-MTD on the growth and viability of human bladder cancer cells. To find out whether anti-proliferation and cell death were associated with apoptosis, we used flow cytometry to quantify the extent of apoptosis and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay to measures DNA degradation of apoptotic cells. The proteins involved in the 13-MTD induced apoptosis were examined using Western blot.


RESULTS
We show that 13-MTD inhibits cellular proliferation and viability in human bladder cancer cells, which has been attributed to apoptosis. 13-MTD down-regulates Bcl-2 and up-regulates Bax. This promotes mitochondrial dysfunction, leading to the release of cytochrome c from the mitochondria to the cytoplasm, as well as the proteolytic activation of caspases. Moreover, 13-MTD down-regulates AKT phosphorylation and activates phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Up-regulating AKT phosphorylation and down-regulating JNK and P38 phosphorylation could attenuate the13-MTD-induced apoptosis.


CONCLUSIONS
Taken together, these data indicate that 13-MTD induces mitochondrial-mediated apoptosis through regulation of the AKT and MAPK pathways, suggesting 13-MTD is a potential candidate for treatment of human bladder cancer.
Lin
Tianxin
T
Department of Urology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Yin
XinBao
X
Cai
Qingqing
Q
Fan
Xinlan
X
Xu
Kewei
K
Huang
Li
L
Luo
Junhua
J
Zheng
Jianping
J
Huang
Jian
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004305:Dose-Response Relationship, Drug; D005285:Fermentation; D006801:Humans; D020287:In Situ Nick-End Labeling; D008928:Mitochondria / Q000378:metabolism*; D009227:Myristic Acids / Q000494:pharmacology*; D010936:Plant Extracts / Q000494:pharmacology; D013025:Glycine max; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*
D000970:Antineoplastic Agents; D009227:Myristic Acids; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; C027331:13-methyltetradecanoic acid