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.

Oenanthe javanica has been used as a food source and also in traditional folk medicine for its detoxifying properties and anti-microbial effects since ancient times. In this study, we evaluated the effect and mechanism of O. javanica seed methanol extract (OJSE) on adipocyte differentiation by 3T3-L1 preadipocytes. Under non-toxic conditions, OJSE treatment resulted in a dose-dependent inhibition of lipid droplet generation and triglyceride accumulation by suppressing adipocyte differentiation, which are associated with the decreased expression of key proadipogenic transcription factors including CCAAR/enhancer binding protein α, β (C/EBPα, C/EBPβ) and peroxisome proliferator-activated receptor γ (PPARγ). OJSE also significantly inhibited proliferation and differentiation of 3T3-L1 preadipocytes through G1-phase arrest, indicating that OJSE blocked mitotic clonal expansion during adipocyte differentiation. Investigation of the alteration of G1 phase arrest-related proteins indicated a dose-dependent increase in the expression of p21 and reduction in expression of cyclin E, Cdk2, E2F-1 and phospho-Rb by OSJE. Taken together, these results suggest that OJSE inhibits adipocyte differentiation by blocking the mitotic clonal expansion, which is accompanied by preadipocyte cell cycle arrest.

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.