A Novel Non-Aromatic B-Ring Flavonoid: Isolation, Structure Elucidation and Its Induction of Apoptosis in Human Colon Ht-29 Tumor Cell Via the Reactive Oxygen Species-Mitochondrial Dysfunction and Mapk Activation

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作者：Wei, A., Zhou, D., Xiong, C., Cai, Y. & Ruan, J.
期刊：Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 49, 2445-2452 (2011)
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The aim of the present study was to elucidate the chemical structure of a novel non-aromatic B-ring flavonoid (DHEC) isolated from Macrothelypteris viridifrons and to evaluate its putative molecular mechanism of action on induction of apoptosis in human colon HT-29 cancer cell. On the basis of MS, UV, IR, 1D and 2D NMR data, DHEC was identified as 2-(cis-1, 2-dihydroxy-4-oxo-cyclohex-5-enyl)-5-hydroxy-7-ethoxy-chromone. In addition, the cytotoxicity of DHEC and its effect on induction of apoptosis were confirmed by several assays. After treatment of HT-29 cell with DHEC, we observed the accumulation of intracellular reactive oxygen species, the loss of mitochondrial membrane potential, the alteration of expression of the Bcl-2 family members, the releasing of cytochrome c, the cleavage of poly (ADP-ribose) polymerase (PARP), and the activation of caspase-3, -8, and -9. Further analysis showed that the mitogen-activated protein kinase (MAPK) related proteins were stimulated by treatment with DHEC. These results suggest that DHEC exhibits potential anti-cancer activity in HT-29 cell through induction of apoptosis, which may highly be associated with reactive oxygen species-mitochondrial dysfunction as well as activation of MAPK signaling pathway.