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- Title
Minnelide: A Novel Therapeutic That Promotes Apoptosis in Non-Small Cell Lung Carcinoma In Vivo.
- Authors
Rousalova, Ilona; Banerjee, Sulagna; Sangwan, Veena; Evenson, Kristen; McCauley, Joel A.; Kratzke, Robert; Vickers, Selwyn M.; Saluja, Ashok; D’Cunha, Jonathan
- 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 invitro and invivo 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.
- Subjects
APOPTOSIS; CANCER treatment; SMALL cell lung cancer; TRIPTOLIDE; ANTINEOPLASTIC agents; ELECTRIC properties of cells; GENE expression; THERAPEUTICS
- Publication
PLoS ONE, 2013, Vol 8, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0077411