Anticancer effect of SZC015 on pancreatic cancer via mitochondria‐dependent apoptosis and the constitutive suppression of activated nuclear factor κB and STAT3 in vitro and in vivo. Issue 1 (4th August 2018)

• Record Type: Journal Article
• Authors: Song, Yanlin; Gao, Lei; Tang, Zhongyuan; Li, Hailong; Sun, Bin; Chu, Peng; Qaed, Eskandar; Ma, Xiaodong; Peng, Jinyong; Wang, Shisheng; Hu, Min; Tang, Zeyao
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 1(2019:Jan.)
• Page Start: 777
• Page End: 788
• Publication Date: 2018-08-04
• Subjects: apoptosis -- mitochondria -- NF‐κB and STAT3 -- pancreatic cancer -- SZC015; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.26892
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Pancreatic cancer is the fourth leading cause of cancer‐related death worldwide. Advances in therapeutic strategies such as chemotherapy have improved the clinical outcomes for pancreatic cancer patients. However, developing new therapeutic compounds against pancreatic cancer is still urgent due to the poor prognosis. Here, we show that SZC015, an oleanolic acid derivative, exhibits potent inhibitory effect on both pancreatic cancer cells in vitro and the corresponding xenograft tumors in vivo. Mechanistically, the activation of intrinsic apoptosis and G1 phase arrest resulting from mitochondria damage caused by SZC015 contribute significantly to the anticancer effects of SZC015. SZC015 also has remarkably inhibitory effects on the transcription factors that are extensively activated in pancreatic cancer tissues. As a constitutively activated transcription factor in pancreatic cancer, the nuclear factor κB is highly suppressed after SZC015 treatment in vitro or administration in vivo. Based on the bioinformatics analysis of microarray data, we validate that JAK2/STAT3 signaling is indeed activated in the human pancreatic cancer tissues and SZC015 also shows inhibitory effect on this signaling both in vitro and in vivo. These data suggest the potent effects of SZC015 on pancreatic cancer and also provided novel insights into the mechanisms of SZC015 as a new potent candidate for treating pancreatic cancer. Abstract : SZC015, an oleanolic acid derivative, exhibits inhibitory effect on pancreatic cancer both in vitro and in vivo. SZC015‐damaged mitochondria generates excessive reactive oxygen species that eventually impairs the cell proliferation of pancreatic cancer. Two types of vital transcriptional signaling, including nuclear factor κB and STAT3, in pancreatic cancer are highly suppressed by SZC015 both in vitro and in vivo.