TY - JOUR
T1 - Minnelide
T2 - A Novel Therapeutic That Promotes Apoptosis in Non-Small Cell Lung Carcinoma In Vivo
AU - Rousalova, Ilona
AU - Banerjee, Sulagna
AU - Sangwan, Veena
AU - Evenson, Kristen
AU - McCauley, Joel A.
AU - Kratzke, Robert
AU - Vickers, Selwyn M.
AU - Saluja, Ashok
AU - D'Cunha, Jonathan
PY - 2013/10/15
Y1 - 2013/10/15
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0077411
DO - 10.1371/journal.pone.0077411
M3 - Article
C2 - 24143232
AN - SCOPUS:84885439105
SN - 1932-6203
VL - 8
JO - PloS one
JF - PloS one
IS - 10
M1 - e77411
ER -