Minnelide: A Novel Therapeutic That Promotes Apoptosis in Non-Small Cell Lung Carcinoma In Vivo |
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| Authors: | Ilona Rousalova Sulagna Banerjee Veena Sangwan Kristen Evenson Joel A. McCauley Robert Kratzke Selwyn M. Vickers Ashok Saluja Jonathan D’Cunha |
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| Affiliation: | 1. Division of Basic and Translational Research, Department of Surgery, University of Minnesota, Minneapolis, Minnesota, United States of America.; 2. Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota, United States of America.; 3. Department of Cardiothoracic Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.; French National Centre for Scientific Research, France, |
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| Abstract: | BackgroundMinnelide, a pro-drug of triptolide, has recently emerged as a potent anticancer agent. The precise mechanisms of its cytotoxic effects remain unclear.MethodsCell 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.ResultsIn 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.ConclusionIn conclusion, our results provide supporting mechanistic evidence for Minnelide as a potential in NSCLC. |
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