Goniothalamin enhances TRAIL-induced apoptosis in colorectal cancer cells through DR5 upregulation and cFLIP downregulation.
The combination of TNF-related apoptosis-inducing ligand (TRAIL) and bioactive compound to enhance apoptosis in TRAIL-resistant cancer is one of cancer treatment strategies. TRAIL possesses the unique capacity to selectively induce apoptosis in cancer cells both in vitro and in vivo with little effect on normal cells. Recent studies have reported that there are many TRAIL-resistant cancers. Thus, bioactive compounds that enhance cytotoxicity of TRAIL would be potential candidates for cancer therapeutic application. This study evaluated the cytotoxic and apoptosis induction upon combined treatment of TRAIL and goniothalamin, the natural styryl-lactone compound extracted from plant Goniothalamus spp., in LoVo cells. The results showed that a combination of goniothalamin and TRAIL enhanced caspase-dependent apoptosis induction in LoVo cells via both death receptor- and mitochondrial-mediated apoptosis pathways. In addition, goniothalamin enhanced TRAIL-induced apoptosis through increased death receptor DR5 expression and decreased anti-apoptotic regulator cFLIP. Interestingly, goniothalamin increased translocation of DR5 to cell surface and consequently contributed to the enhancement of TRAIL-induced apoptosis. In conclusion, this is the first report showing the combined treatment of goniothalamin and TRAIL was able to effectively enhance TRAIL-mediated apoptosis induction in TRAIL-refractory colorectal cancer, LoVo cells. Therefore, this study may offer a strategic cancer treatment against TRAIL-resistant cancers.
Department of Biochemistry, Faculty of Medicine, Srinkharinwirot University, Bangkok 10110, Thailand.
Thanet
T
Sophonnithiprasert
Department of Biochemistry, Faculty of Medicine, Srinkharinwirot University, Bangkok 10110, Thailand.
Sirinun
S
Nilwarangkoon
Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Yukio
Y
Nakamura
Department of Biochemistry, Faculty of Medicine, Srinkharinwirot University, Bangkok 10110, Thailand.
Ramida
R
Watanapokasin
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000494:pharmacology; D018547:Plant Stems; D016133:Polymerase Chain Reaction; D011753:Pyrones / Q000494:pharmacology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation
D000972:Antineoplastic Agents, Phytogenic; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; C506386:CFLAR protein, human; D010936:Plant Extracts; D011753:Pyrones; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; C103280:goniothalamin