Induction of G1 Arrest by Methanol Extract of Lycopus lucidus in Human Lung AdenocarcinomaA549 Cells Lycopus lucidus, a herbaceous perennial, is used as a traditional remedy in East Asia, including China and Korea. It has been reported that L. lucidus has anti-allergic effects, inhibitory effects on cholesterol acyltransferase in high glucose-induced vascular inflammation, and anti-proliferative effects in human breast cancer cells. However, the molecular mechanisms of the anti-cancer effects of L. lucidus have not yet been fully determined. In this study, we evaluated the anti-cancer effect and the mechanism of action of L. lucidus in human lung adenocarcinoma A549 cells using methanol extracts of L. lucidus (MELL). MELL treatment showed cytotoxic activity in a dose-dependent manner and induced G1 arrest in A549 cells. The induction of G1 arrest by MELL was associated with the up-regulation of phospho-CHK2 and the down-regulation of Cdc25A phosphatase. In addition, MELL treatment induced decreased expression of G1/S transition-related proteins, including CDK2, CDK4, CDK6, cyclin D1 and cyclin E. MELL also regulated the mRNA expression of CDK2 and cyclin E. On the other hand, the expression of p53 and the cyclin-dependent kinase inhibitor p21 was not induced by MELL. Collectively, these results suggest that MELL may exert an anti-cancer effect by cell cycle arrest at G1 phase through the ATM/CHK2/Cdc25A/CDK2 pathway in A549 cells.

Treculia africana Decne, a breadfruit species, is native to many parts of West and Tropical Africa. The breadfruit belongs to the family Moraceae and is one of the four members of the genera Treculia. The crude extract of T. africana has been used in folk medicine as an anti-inflammatory agent for various ailments, such as whooping cough. In this study, we evaluated the anti-oxidative and anti-cancer activities of the methanol extract of T. africana Decne (META) and the molecular mechanisms of its anti-cancer effects in human colon carcinoma HT29 cells. The META exhibited anti-oxidative activity through a DPPH radical scavenging capacity and inhibited cell growth in a dose-dependent manner in HT29 cells. META treatment induced apoptosis of HT29 cells, showing an increase in the percentage of both SubG1 cells and Annexin V-positive cells and the formation of apoptotic bodies in a dose-dependent manner. META-mediated apoptosis was associated with the up-regulation of the death receptor FAS and Bax and a decrease in the Bcl-2 expression. META-treated HT29 cells also showed the release of cytochrome c from the mitochondria into the cytosol, activation of caspase-3, caspase-8, and caspase-9, and proteolytic cleavage of poly ADP-ribose polymerase (PARP). These findings suggest META may exert an anti-cancer effect in HT29 cells by inducing apoptosis through both intrinsic and extrinsic pathways.

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Julbernardia globiflora, a tropical African tree widespread in Miombo woodland, has been used in folk medicine for the treatment of depression and stomach problems. However, the antioxidative and anticancer activities of J. globiflora remain unclear. The objective of this study is to evaluate the antioxidative and anticancer effects of methanol extract of J. globiflora (MEJG) and the molecular mechanism of its anticancer activity in human colon carcinoma HT29 cells. MEJG exhibited significant antioxidative effect with an IC50 (concentration at 50% inhibition) value of 1.23 μg/ml measuring by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay and inhibited cell proliferation in a dose-dependent manner in HT29 cells. We found that MEJG induced apoptosis of HT29 cells with the increase of apoptotic cells and apoptotic bodies using Annexin V staining and 4,6-diamidino-2-phenylindole (DAPI) staining, respectively. The MEJG treatment showed the increase of Fas, a death receptor, and Bax, a pro-apoptotic protein, and the decrease of Bcl-2, an anti-apoptotic protein, resulting in the release of cytochrome c from the mitochondria into the cytosol and activation of caspase-3, -8 and -9. The apoptotic effects of MEJG were confirmed by cleavage of poly (ADP-ribose) polymerase (PARP). Collectively, these results suggest that MEJG may exert the anticancer effect in HT29 cells by inducing apoptosis via both the intrinsic and extrinsic pathways.