title: 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.
abstract: 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.
authors: Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation of Hubei Province, College of Pharmacy, Huazhong University of Science and Technology, Wuhan, China.
authors: Anhua
authors: A
authors: Wei
authors: Daonian
authors: D
authors: Zhou
authors: Chaomei
authors: C
authors: Xiong
authors: Yaling
authors: Y
authors: Cai
authors: Jinlan
authors: J
authors: Ruan
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D004789:Enzyme Activation; D005419:Flavonoids / Q000737:chemistry / Q000494:pharmacology*; D019073:HT29 Cells; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D005419:Flavonoids; D017382:Reactive Oxygen Species; D020928:Mitogen-Activated Protein Kinases; D000111:Acetylcysteine