Colon cancer is the third most common
malignancy around the world. Surgery,
chemotherapy, and
radiotherapy are generally used to treat
colon cancer, but no effective
therapy for advanced colon
carcinoma is available. Therefore, there is a need to identify other therapeutic agents against this disease.
Magnolol, a hydroxylated
biphenyl compound present in Magnolia officinalis, exerts anticancer potential and low toxicity. Emerging evidence has suggested that activation of
AMP-activated protein kinase (AMPK), a potential
cancer therapeutic target is involved in apoptosis in
colon cancer cells. However, the effects of
magnolol on human
colon cancer through activation of AMPK remain unexplored. In this study, we explored whether
magnolol exerts an antiproliferative effect, and induces apoptosis in HCT-116 human
colon cancer cells.
Magnolol displayed several apoptotic features, including
propidium iodide labeling, DNA fragmentation, and
caspase-3 and
poly(ADP-ribose) polymerase cleavages. We showed that
magnolol induced the phosphorylation of AMPK in dose- and time-dependent manners. The selective
AMPK inhibitor compound C abrogated the effect of
magnolol on AMPK activation, suppression of proliferation, and
caspase-3 cleavage.
Magnolol downregulated expression of the antiapoptotic
protein Bcl2, upregulated expression of
pro-apoptotic protein p53 and Bax, and caused the release of mitochondrial
cytochrome c.
Magnolol-induced p53 and Bcl2 expression was abolished in the presence of compound C.
Magnolol inhibited migration and invasion of HCT-116 cells through AMPK activation. These findings demonstrate that AMPK mediates the anticancer effects of
magnolol through apoptosis in HCT-116 cells.