[HTML][HTML] Minnelide: a novel therapeutic that promotes apoptosis in non-small cell lung carcinoma in vivo

I Rousalova, S Banerjee, V Sangwan, K Evenson… - PloS one, 2013 - journals.plos.org
I Rousalova, S Banerjee, V Sangwan, K Evenson, JA McCauley, R Kratzke, SM Vickers
PloS one, 2013journals.plos.org
Background Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer
agent. The precise mechanisms of its cytotoxic effects remain unclear. Methods Cell viability
was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells
using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by
Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections.
Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA …
Background
Minnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear.
Methods
Cell viability was studied using CCK8 assay. Cell proliferation was measured real-time on cultured cells using Electric Cell Substrate Impedence Sensing (ECIS). Apoptosis was assayed by Caspase activity on cultured lung cancer cells and TUNEL staining on tissue sections. Expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA, APAF-1) was estimated by qRTPCR. Effect of Minnelide on proliferative cells in the tissue was estimated by Ki-67 staining of animal tissue sections.
Results
In this study, we investigated in vitro and in vivo antitumor effects of triptolide/Minnelide in non-small cell lung carcinoma (NSCLC). Triptolide/Minnelide exhibited anti-proliferative effects and induced apoptosis in NSCLC cell lines and NSCLC mouse models. Triptolide/Minnelide significantly down-regulated the expression of pro-survival and anti-apoptotic genes (HSP70, BIRC5, BIRC4, BIRC2, UACA) and up-regulated pro-apoptotic APAF-1 gene, in part, via attenuating the NF-κB signaling activity.
Conclusion
In conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC.
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