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.
Highlights
Andrographolide (Andro) is a diterpenoid lactone isolated from the functional herb Andrographis paniculata, which has been used as a folk medicine to treat upper respiratory infections, sore throats and many other infectious diseases
Human prostate carcinoma DU145 cells were exposed to 0 to 50 mM Andro for 24, 48 and 72 h, and cell proliferation was assessed using the MTT assay, a common method to measure the metabolic activity of cells to reflect the cell number or proliferation
Andro inhibited the proliferation of DU145 cells in a time- and concentration-dependent manner compared to untreated proliferating cells (Figure 1A)
Summary
Andrographolide (Andro) is a diterpenoid lactone isolated from the functional herb Andrographis paniculata, which has been used as a folk medicine to treat upper respiratory infections, sore throats and many other infectious diseases. This compound has been suggested to have great potential for cancer treatment because it shows anticancer activities in both direct and indirect ways [1,2,3,4,5]. Our recent study shows that the effects of Andro are dependent on the cell type It arrests the cell cycle at G2/M in several hepatocellular cancer cell lines, but it leads to apoptosis in HeLa cells [16]
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