Constituents of Amoora cucullata with TRAIL resistance-overcoming activity.
In search of bioactive natural products for overcoming TRAIL resistance from natural resources, we previously reported a number of active compounds. Bioassay-guided fractionation of mangrove, Amoora cucullata, collected from Sundarbans Mangrove Forest, Bangladesh, led to the isolation of four new compounds (1-4), along with seven known compounds (5-11). Of the isolates, compounds 1, 5, 8, and 9 showed TRAIL resistance-overcoming activity, among which 8 showed the most potent activity and enhanced TRAIL-induced apoptosis in TRAIL-resistant human gastric adenocarcinoma (AGS) cells through the activation of caspase-3/7, enhancing the expression of DR4 and DR5 mRNA in AGS cells. Cell death caused by the combined treatment of 8 and TRAIL was inhibited by human recombinant DR5/Fc and DR4/Fc chimera proteins, indicating that 8 sensitizes TRAIL-resistant AGS cells to TRAIL through the induction of DR4 and DR5.
Ahmed
Firoj
F
Graduate School of Pharmaceutical Sciences, Chiba University, 1-33 Yoyoi-cho, Inage-ku, Chiba 263-8522, Japan.
Toume
Kazufumi
K
Sadhu
Samir K
SK
Ohtsuki
Takashi
T
Arai
Midori A
MA
Ishibashi
Masami
M
D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D029582:Meliaceae / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000037:antagonists & inhibitors* / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics
D010936:Plant Extracts; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; C105190:TNFRSF10A protein, human; C505407:CASP3 protein, human; C505520:CASP7 protein, human; D053148:Caspase 3; D053179:Caspase 7