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.

A map describing the association between effective components of traditional Chinese medicine and signaling pathways in cancer cells in vitro and in vivo

“…The combination of androgarpholide and taxifolin inhibit proliferation and trigger apoptosis of breast cancer cells by disrupting microtubule dynamics and acitivating the spindle assembly checkpoint (SAC) (21). In other studies, androgarpholide alone can inhibit proliferation of breast cancer cells and non-small cell lung cancer (NSCLC) cells by downregulating the PI3K/Akt pathway (22,23).…”

Plant flavonoid taxifolin inhibits the growth, migration and invasion of human osteosarcoma cells

“…Taxifolin, also known as dihydroquercetin, exhibits strong antioxidant abilities Taxifolin, also known as dihydroquercetin, exhibits strong antioxidant ability (10). The properties of taxifolin are similar to quercetin, which has been demonstrated to induce apoptosis in cell and animal models (10,11).…”

Daucosterol inhibits cancer cell proliferation by inducing autophagy through reactive oxygen species-dependent manner

“…Bioassay-guided analysis of ethyl acetate fraction identified eight compounds, including epigallocatechin-3-gallate (ECCG), kaempferol, naringenin, beta-sitosterol, resveratrol, taxifolin and daucosterol. The anti-cancer effects of ECCG [5,6], kaempferol [7,8], naringenin [9,10], beta-sitosterol [11,12], resveratrol [13,14] and taxifolin [15] were all reported previously. Daucosterol is not endogenously synthesized but can be obtained through diet.…”