Apoptosis and antimigration induction in human skin cancer cells by rhodomyrtone.

Rhodomyrtone is a bioactive compound extracted from Rhodomyrtus tomentosa leaves. It has been used as a traditional herb medicine for many years. Rhodomyrtone exhibits antibacterial activity, anti-inflammatory and antioxidant activities. However, the anticancer activity of rhodomyrtone has not been previously reported. The present study investigated the anticancer effect of rhomyrtone on human epidermoid carcinoma A431 cells. The cytotoxic and antiproliferative effects of rhodomyrtone on A431 cells were investigated by an MTT assay. Cell morphological alterations and apoptotic cells were observed with Hoechst 33342 staining following rhodomyrtone treatment. Flow cytometry and western blotting were performed to detect cell cycle and apoptosis induction. The results demonstrated that rhodomyrtone inhibited proliferation of A431 cells in a dose-dependent manner with IC50 value of 8.04±0.11 µg/ml. The results also indicated that rhodomyrtone increased chromatin condensation, nuclear fragmentation and apoptotic bodies in treated A431 cells in a time-dependent manner. Apoptosis was also induced through the activation of caspase-7 and poly (ADP-Ribose) polymerase cleavage. Flow cytometry analysis revealed that rhodomyrtone induced cell cycle arrest at the G1 phase. Notably, the non-toxic concentration of rhodomyrtone markedly inhibited A431 cell migration in a dose- and time-dependent manner. These finding suggested that rhodomyrtone may be used as an anticancer agent for human skin cancer.

p38 inhibitor inhibits the apoptosis of cowanin-treated human colorectal adenocarcinoma cells.

Colorectal cancer, which is the third most common type of cancer diagnosed in both men and women, is the leading cause of cancer-related deaths worldwide. Cowanin is a pure compound extracted from Garcinia cowa Roxb., a tree species present in Thailand, Malaysia and Myanmar. The crude extract has been demonstrated to have antitumor activity, inflammation induction, antibacterial activity, anti-inflammatory activity and antimalarial activity. In the present study, the effects of cowanin on apoptosis induction and on the apoptosis-related and mitogen-activated protein kinase (MAPK) pathways were investigated in the LoVo human colorectal cancer cell line. The cytotoxicity of cowanin in LoVo cells was determined by MTT assay. Hoechst 33342 and JC­1 staining were used to determine nuclear morphological changes and mitochondrial membrane potential, respectively. The expression levels of BCL2 apoptosis regulator (Bcl­2) family, MAPK and AKT serine/threonine kinase 1 (Akt) pathway proteins following cowanin treatment were determined by western blot analysis. The results demonstrated that cowanin inhibited cell proliferation and induced cell death via the apoptosis pathway. Cowanin treatment increased BCL2 associated X (Bax) and decreased Bcl­2 expression. In addition, cowanin activated caspase­9, -7 and poly-ADP-ribose-polymerase expression. Furthermore, cowanin decreased the levels of phosphorylated extracellular signal-regulated kinase (p­ERK), p­Akt, p­3­phosphoinositide­dependent protein kinase­1, while it increased p­p38 expression, thus resulting in the induction of apoptosis. In conclusion, cowanin inhibited cell proliferation and induced apoptosis of LoVo cells via the MAPK and Akt signaling pathways. Notably, inhibition of p38 by using a p38 inhibitor (SB203580) prevented the cowanin-induced apoptosis in LoVo cells. These results suggested that cowanin may be a potential candidate for the treatment of colorectal cancer and provided important information on the molecular mechanisms underlying its antitumor activity.