title: Taxifolin enhances andrographolide-induced mitotic arrest and apoptosis in human prostate cancer cells via spindle assembly checkpoint activation.
abstract: Andrographolide (Andro) suppresses proliferation and triggers apoptosis in many types of cancer cells. Taxifolin (Taxi) has been proposed to prevent cancer development similar to other dietary flavonoids. In the present study, the cytotoxic and apoptotic effects of the addition of Andro alone and Andro and Taxi together on human prostate carcinoma DU145 cells were assessed. Andro inhibited prostate cancer cell proliferation by mitotic arrest and activation of the intrinsic apoptotic pathway. Although the effect of Taxi alone on DU145 cell proliferation was not significant, the combined use of Taxi with Andro significantly potentiated the anti-proliferative effect of increased mitotic arrest and apoptosis by enhancing the cleavage of poly(ADP-ribose) polymerase, and caspases-7 and -9. Andro together with Taxi enhanced microtubule polymerization in vitro, and they induced the formation of twisted and elongated spindles in the cancer cells, thus leading to mitotic arrest. In addition, we showed that depletion of MAD2, a component in the spindle assembly checkpoint (SAC), alleviated the mitotic block induced by the two compounds, suggesting that they trigger mitotic arrest by SAC activation. This study suggests that the anti-cancer activity of Andro can be significantly enhanced in combination with Taxi by disrupting microtubule dynamics and activating the SAC.
authors: Research Group for Bioactive Products, Department of Biology and Chemistry, City University of Hong Kong, Hong Kong SAR, China.
authors: Zhong Rong
authors: ZR
authors: Zhang
authors: Mazen
authors: M
authors: Al Zaharna
authors: Matthew Man-Kin
authors: MM
authors: Wong
authors: Sung-Kay
authors: SK
authors: Chiu
authors: Hon-Yeung
authors: HY
authors: Cheung
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology* / Q000633:toxicity; D004357:Drug Synergism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D008297:Male; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity
chemical_list: D018797:Cell Cycle Proteins; D004224:Diterpenes; D019253:Proto-Oncogene Proteins c-bcl-2; C030419:andrographolide; D011794:Quercetin; C003377:taxifolin; D020169:Caspases
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