Magnolol suppresses proliferation of cultured human colon and liver cancer cells by inhibiting DNA synthesis and activating apoptosis

Abstract

Magnolol, a hydroxylated biphenyl compound isolated from the Chinese herb Hou p'u of Magnolia officinalis, has been reported to have anti-cancer activity. In the present study, magnolol at very low concentrations of 3-10 microM inhibited DNA synthesis and decreased cell number in cultured human cancer cells (COLO-205 and Hep-G2) in a dose-dependent manner, but not in human untransformed cells such as keratinocytes, fibroblasts, and human umbilical vein endothelial cells (HUVEC). Magnolol was not cytotoxic at these concentrations and this indicates that it may have an inhibitory effect on cell proliferation in the subcultured cancer cell lines. [(3)H] thymidine incorporation and flow cytometry analyses revealed that magnolol treatment decreased DNA synthesis and arrested the cells at the G0/G1 phase of the cell cycle. Moreover, the magnolol-induced cell cycle arrest occurred when the cyclin-CDK system was inhibited, just as p21 protein expression was augmented. When magnolol concentration was increased to 100 microM, apoptosis was observed in COLO-205 and Hep-G2 cells, but not in cultured human fibroblasts and HUVEC. COLO-205 cells implanted subcutaneously in nude mice formed solid tumors; subsequent daily i.p.-injections of magnolol led to profound regression of these tumors of up to 85%. In these tumors, an increase in the expression of p21 protein level and the occurrence of apoptosis were observed. These findings demonstrate for the first time that magnolol can inhibit the proliferation of tumor cells in vitro and in vivo.

Magnolol-Induced Apoptosis in HCT-116 Colon Cancer Cells Is Associated with the AMP-Activated Protein Kinase Signaling Pathway

“…Many researchers have shown the various anticancer activities of magnolol. For example, magnolol suppresses proliferation of cultured human colon cancer cells by inhibiting DNA synthesis 21) ; magnolol-induced apoptotic death is mediated by blocking the EGFR-PI3K-Akt pathway and subsequent activation of the Bad-Bax-cytochrome c-caspase pathway in human prostate cancer cells 18) ; magnolol decreases cell number in a cultured human glioblastoma (U373) cancer cell line 20) ; magnolol (100 µM) induces apoptosis in cultured human hepatoma (Hep G2) and colon cancer (COLO 205) cell lines. 26) More recently, magnolol-induced apoptosis in human gastric adenocarcinoma (SGC-7901) cells by mitochondrial and PI3K-Akt signaling pathways, 27) and magnolol has anticarcinogenic effects against UVB-induced skin tumor development in SKH-1 mice and a possible role in apoptosis during skin tumor development has been determined.…”

“…18) Attention has been paid to its anticancer activity in several cancer cell lines, including colon cancer, hepatoma, leukemia, fibrosarcoma, melanoma, squamous carcinoma, and thyroid carcinoma. 18,19) Several researchers have shown that magnolol inhibits proliferation and induces apoptosis in cancer cells by upregulating p21 cip/Waf1 , 20) inhibiting DNA synthesis, 21) activating the epidermal growth factor receptor (EGFR)/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, 18) as well as Ras/Raf-1/ Erk actions. 22) However, it remains to be determined whether Note * To whom correspondence should be addressed.…”

Honokiol, a natural biphenyl, inhibits in vitro and in vivo growth of breast cancer through induction of apoptosis and cell cycle arrest

“…These anti-angiogenesis effects are attributed to HNK-induced suppression of vascular endothelial growth factor receptor R2 (KDR) phosphorylation, thus leading to inhibition of the mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3-kinase) pathways (19). Additional recognized activities of HNK include cytochrome C release and increased cytosolic free calcium (20)(21)(22).…”

Phenylpropanoids, Eugenol Scaffold, and Its Derivatives as Anticancer

“…These findings demonstrate that AMPK mediates the anticancer effects of magnolol through apoptosis in HCT-116 cells. Several researchers have shown that magnolol inhibits proliferation and induces apoptosis in cancer cells by inhibiting DNA synthesis [25], signaling pathway as well as Ras/Raf-1/Erk actions [26]. However, it remains to be determined whether apoptotic cell death is associated with the AMPK signaling pathway in HCT-116 colon cancer cells treated with magnolol.…”