The present study demonstrates that the combination of TRAIL/APO-2L and celastrol exerts strong synergistic antiproliferative effect against human cancer cells including ovary cancer OVCAR-8, colon cancer SW620, and lung cancer 95-D, with the combination indices below 0.8. Moreover, the in vivo antitumor efficacy of TRAIL/APO-2L was dramatically increased by celastrol. These enhanced anticancer activities were accompanied by the prompt onset of caspase-mediated apoptosis. Taken together, our data firstly demonstrate the synergistic anticancer capabilities achieved by combining TRAIL/APO-2L and celastrol, and moreover, open new opportunities to enhance the effectiveness of future treatment regimens using TRAIL/APO-2L.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.3109/07357900903095664 | DOI Listing |
Oncotarget
December 2016
Department of Orthopaedics, Affiliated Hospital, Guilin Medical University, Guilin, Guangxi, China.
γδ T cells has been shown to exhibit profound antitumor effects in a broad range of tumor entities, including OS. However, resistance to γδ T cells is a serious problem in the management of OS. This study investigates the impact of celastrol on the expression of death receptors 4/5 (DR4/5) on OS cell lines (HOS, U2OS) and cancer cell lysis by γδ T cells.
View Article and Find Full Text PDFCancer Lett
November 2010
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
Our previous study demonstrated that celastrol combined with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo-2L) exhibited significant synergistic anti-cancer activities, thus we were promoted to investigate the molecular mechanism of this synergy. Here in this study, we show that celastrol up-regulates death receptor 4 (DR4) and 5 (DR5) expression at mRNA, total protein and cell surface levels, and the specific knockdown using DR4- or DR5-targeting siRNA transfection attenuates the PARP cleavage caused by the combination of celastrol and TRAIL/Apo-2L, denoting the critical roles of DR induction in this sensitization. Of note is that although celastrol activates p38 mitogen activated protein kinases (p38 MAPK), SB203580, one specific inhibitor of p38, fails to interrupt celastrol-induced DR4 expression and the enhanced apoptosis caused by celastrol plus TRAIL/Apo-2L.
View Article and Find Full Text PDFCancer Invest
January 2010
Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, 310058 China.
The present study demonstrates that the combination of TRAIL/APO-2L and celastrol exerts strong synergistic antiproliferative effect against human cancer cells including ovary cancer OVCAR-8, colon cancer SW620, and lung cancer 95-D, with the combination indices below 0.8. Moreover, the in vivo antitumor efficacy of TRAIL/APO-2L was dramatically increased by celastrol.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!