LTP-1, a novel antimitotic agent and Stat3 inhibitor, inhibits human pancreatic carcinomas in vitro and in vivo

• Published in: Scientific reports Vol. 6; no. 1; p. 27794
• Main Authors: Huang, Han-Li, Chao, Min-Wu, Chen, Chung-Chun, Cheng, Chun-Chun, Chen, Mei-Chuan, Lin, Chao-Feng, Liou, Jing-Ping, Teng, Che-Ming, Pan, Shiow-Lin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09.06.2016; Nature Publishing Group
• Subjects: 13/31; 13/95; 14/19; 631/67/1059/153; 692/4028/67/1059; Animals; Antimitotic Agents - administration & dosage; Antimitotic Agents - pharmacology; Apoptosis; Arylsulfonic Acids - administration & dosage; Arylsulfonic Acids - pharmacology; Cell cycle; Cell growth; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Cyclin-dependent kinases; Gene Expression Regulation, Neoplastic - drug effects; Humanities and Social Sciences; Humans; Kinases; Mice; multidisciplinary; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - metabolism; Pharmacy; Phosphorylation; Phosphorylation - drug effects; Polymerization; Science; STAT3 Transcription Factor - metabolism; Xenograft Model Antitumor Assays; Taiwan
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep27794

Pancreatic cancer is the leading cause of cancer death worldwide with a poor survival rate. The objective of this study was to determine the mechanism of action of a novel antimitotic and Stat3 inhibitor, LTP-1, on human pancreatic cancer in vitro and in vivo . We found that LTP-1 inhibited pancreatic cancer cell growth and viability with significant G 2 /M arrest and disruption of microtubule dynamics. LTP-1 also caused G 2 /M arrest-independent Stat3 dephosphorylation along with ERK activation, which indicated the possible dual function of LTP-1. Long-term treatment of LTP-1 also induced polyploidy, activated caspases, induced subG 1 cell population and therefore, triggered pancreatic cancer cell apoptosis. Finally, we used an in viv o xenograft model to demonstrate that LTP-1 suppressed the growth of pancreatic adenocarcinoma. In summary, our data suggest that LTP-1 may alter microtubule dynamics, which ultimately causes polyploidy and apoptosis, thereby inhibiting pancreatic cancer growth in vitro and in vivo . This study provides evidence that LTP-1 could be a potential therapeutic agent for further development of pancreatic cancer treatment.