Minnelide: A Novel Therapeutic That Promotes Apoptosis in Non-Small Cell Lung Carcinoma In Vivo

Ilona Rousalova, Sulagna Banerjee, Veena Sangwan, Kristen Evenson, Joel A. McCauley, Robert Kratzke, Selwyn M. Vickers, Ashok Saluja, Jonathan D'Cunha

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article numbere77411
JournalPloS one
Volume8
Issue number10
DOIs
StatePublished - Oct 15 2013

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    Rousalova, I., Banerjee, S., Sangwan, V., Evenson, K., McCauley, J. A., Kratzke, R., Vickers, S. M., Saluja, A., & D'Cunha, J. (2013). Minnelide: A Novel Therapeutic That Promotes Apoptosis in Non-Small Cell Lung Carcinoma In Vivo. PloS one, 8(10), [e77411]. https://doi.org/10.1371/journal.pone.0077411