A rice bran polyphenol, cycloartenyl ferulate, elicits apoptosis in human colorectal adenocarcinoma SW480 and sensitizes metastatic SW620 cells to TRAIL-induced apoptosis.
High intake of whole grain food has been suggested as an important factor for reducing the risk of colon cancer, owing to the abundance of indigestible fibers. Our findings demonstrated that, among various rice bran phenolic compounds tested, cycloartenyl ferulate (CF) showed the most prominent in vitro growth inhibition on human colorectal adenocarcinoma SW480, but had low toxicity on normal colon CCD-18-Co cells. The anticancer activity of CF was further illustrated by its ability to induce significant regression of SW480 xenograft in nude mice. CF elevated the death receptors DR4 and DR5 and triggered both the death receptor and the mitochondrial apoptosis pathways. Depletion of anti-apoptotic Bcl-2 and up-regulation of pro-apoptotic Bak were observed, accompanied by dissipation of the mitochondrial membrane potential and release of cyto c and SMAC/DIABLO from mitochondria into the cytosol. Bid was found to be cleaved by caspase-8, so that the death receptor pathway might be exaggerated by the mitochondrial pathway. Strikingly, we showed for the first time that CF also sensitized the metastatic and resistant colon cancer SW620 to TRAIL-induced apoptosis and the mechanisms involved at least enhanced activation of caspase-8 and -3. This study provides a clear evidence that the health-beneficial properties of whole grain consumption are not only limited by the presence of dietary fibers but also other molecules that can either act as a chemopreventive agent to directly induce tumor regression or as a sensitizer to enhance TRAIL-induced apoptosis in metastatic cancer cells.
Kong
Carrie K L
CK
Department of Biology and the State Key Laboratory of Agrobiotechnology (CUHK), The Chinese University of Hong Kong, Hong Kong SAR, China.
Lam
W S
WS
Chiu
Lawrence C M
LC
Ooi
Vincent E C
VE
Sun
Samuel S M
SS
Wong
Yum-Shing
YS
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology*; D000700:Analgesics / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D002470:Cell Survival; D003106:Colon / Q000166:cytology / Q000473:pathology; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000473:pathology*; D003373:Coumaric Acids / Q000302:isolation & purification / Q000494:pharmacology*; D004357:Drug Synergism; D005419:Flavonoids / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012275:Oryza / Q000737:chemistry*; D010636:Phenols / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use; D059808:Polyphenols; D011485:Protein Binding; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000096:biosynthesis / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology* / Q000627:therapeutic use; D023041:Xenograft Model Antitumor Assays
D000700:Analgesics; D003373:Coumaric Acids; D005419:Flavonoids; D010636:Phenols; D059808:Polyphenols; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D011994:Recombinant Proteins; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C540967:cycloartenyl ferulate