Methyl jasmonate down-regulates survivin expression and sensitizes colon carcinoma cells towards TRAIL-induced cytotoxicity

Abstract

BACKGROUND AND PURPOSEMethyl jasmonate (MJ) is a plant stress hormone with selective cytotoxic anti-cancer activities. The TNF-related apoptosis-inducing ligand (TRAIL) death pathway is an attractive target for cancer therapy. Although TRAIL receptors are specifically expressed in primary cancer cells and cancer cell lines, many types of cancer cells remain resistant to TRAILinduced cytotoxicity. Here we have assessed a possible synergy between MJ and TRAIL cytotoxicity in colorectal cancer (CRC) cell lines. EXPERIMENTAL APPROACHCRC cell lines were pre-incubated with sub-cytotoxic concentrations of MJ followed by TRAIL administration. Cell death was determined by XTT assay and microscopy. Cytochrome c release, caspase cleavage, TRAIL-associated factors, X-linked inhibitor of apoptosis (XIAP) and survivin protein levels were detected by immunoblotting. Survivin transcription was examined by RT-PCR. KEY RESULTSPre-treatment with MJ resulted in increased TRAIL-induced apoptotic cell death, increased cytochrome c release and caspase cleavage. TNFRSF10A, TNFRSF10B, TNFRSF10D, Fas-associated death domain and cellular FLICE-like inhibitory protein remained unchanged during MJ-induced TRAIL sensitization, whereas MJ induced a significant decrease in survivin protein levels. Overexpression of survivin prevented MJ-induced TRAIL cytotoxicity, implying a role for survivin in MJ-induced TRAIL sensitization. MJ decreased survivin mRNA indicating that MJ may affect survivin transcription. In a b-catenin/transcription factor (TCF)-dependent luciferase activity assay, MJ decreased TCF-dependent transcriptional activity. CONCLUSION AND IMPLICATIONSMJ, at sub-cytotoxic levels, sensitized CRC cells to TRAIL-induced apoptosis. Thus, combinations of MJ and TRAIL, both selective anti-cancer agents, have potential as novel treatments for CRC. AbbreviationscFLIP, cellular FLICE-like inhibitory protein; CRC, colorectal cancer; FADD, Fas-associated death domain; IAP, inhibitors of apoptosis; MJ, methyl jasmonate; PARP, poly ADP ribose polymerase; TRAIL, TNF-related apoptosis-inducing ligand

EZH2 inhibition promotes methyl jasmonate‑induced apoptosis of human colorectal cancer through the Wnt/β‑catenin pathway

“…In the present study, it was revealed that the anticancer effect of methyl jasmonate downregulates Wnt/β-catenin expression in human colorectal cancer cells. Raviv et al (28) previously reported that methyl jasmonate downregulated survivin expression and sensitized colon carcinoma cells through the β-catenin pathway.…”

Protective Effect of Caffeic Acid on Paclitaxel Induced Anti-Proliferation and Apoptosis of Lung Cancer Cells Involves NF-κB Pathway

“…Numerous studies have demonstrated that down-regulation or inactivation of pro-survival proteins, including survivin and Bcl-2 [23], promotes anti-cancer efficacy or sensitizes tumor cells toward chemotherapeutic drugs in human tumor cells [24]. …”

Down-Regulation of Survivin by Nemadipine-A Sensitizes Cancer Cells to TRAIL-Induced Apoptosis

“…However, the expression level of survivin was remarkably reduced in nemadipine-A treated cells. It has been well documented that the down-regulation of survivin by chemotherapeutic agents sensitizes cancer cells to TRAIL-induced apoptosis (Kim et al ., 2004; Lu et al ., 2008; Raviv et al ., 2011). Consistently, we have also found that nemadipine-A potentiates TRAIL-induced apoptosis by reducing survivin expression.…”