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.

Involvement of both extracellular signal‐regulated kinase and c‐jun N‐terminal kinase pathways in the 12‐O‐tetradecanoylphorbol‐13‐acetate–induced upregulation of p21Cip1 in colon cancer cells

“…As previously described [16,17], the cells were seeded on 100 mm‐dishes and grown in RPMI‐1640 supplemented with 10% FCS. After the cells had grown to subconfluence, they were treated with 0.1% DMSO with or without 100 nM TPA (control).…”

Magnolol inhibits growth of gallbladder cancer cells through the p53 pathway

“…Magnolol, a primary active ingredient of the Chinese medicinal herb Magnolia officinalis , displays a variety of pharmacological activities including anti‐oxidant and anti‐inflammatory activities and central nervous system depressant effects . Recent studies have indicated that magnolol induces antiproliferative effects by blocking DNA synthesis and by inducing apoptosis and cell cycle arrest in a wide variety of tumor cells including colon, liver, and ovarian cancer cells . However, the effects and mechanism of magnolol on human GBC cells have never been elucidated.…”

Progesterone Inhibits Endothelial Cell Migration Through Suppression of the Rho Activity Mediated by cSrc Activation

“…To determine the expression levels of cSrc, p‐cSrc, FAK, paxillin, RhoA, RhoB, RhoC, Rac‐1, cadherin, and G3PDH in HUVECs, the total proteins were extracted and Western blot analyses were performed as previously described [Lin et al, ]. Briefly, HUVECs were cultured in 10 cm Petri dishes.…”