Sorbus commixta water extract induces apoptotic cell death via a ROS-dependent pathway.

The stembark of Sorbus commixta Hedl. has been used for treating asthma, bronchitis, gastritis and edema. However, the anticancer and proapoptotic effects of the water extract of the stembark of S. commixta (SCE) remain unknown. In the present study, it was shown that SCE inhibited the cell viability of the hepatocellular carcinoma cell lines Hep3B and HepG2, and of the colon carcinoma cell line HCT116. DNA content analysis indicated that SCE increased the sub-G1 population of HCT116 cells. In addition, degradation of nuclear DNA and levels of proapoptotic cascade components, including caspase-9, caspase-3 and poly ADP-ribose polymerase, were augmented by SCE treatment. Mitochondrial membrane potential and the ratio of B-cell lymphoma-2 (Bcl-2)/Bcl-2-associated X protein (Bax) were also reduced. Furthermore, SCE increased the expression of proapoptotic proteins, including p21, p27 and p53. Mouse double minute 2 homology, a negative regulator of p53, was cleaved by SCE treatment. Intracellular reactive oxygen species (ROS) production was also increased by SCE treatment. However, the SCE-induced cytotoxic effects and the increased expression of proapoptotic proteins, including p53 and p21, and reduced Bcl-2/Bax ratio, could be attenuated by N-acetyl cysteine, an ROS inhibitor. Taken together, these results indicate that SCE is a potent proapoptotic herbal medicine, which exerts its effects via the ROS-mediated mitochondrial pathway.

Scutellaria baicalensis Georgi induces caspase-dependent apoptosis via mitogen activated protein kinase activation and the generation of reactive oxygen species signaling pathways in MCF-7 breast cancer cells.

Scutellaria baicalensis Georgi extract (SBGE) is used in traditional herbal medicine and has also been used clinically to ameliorate the symptoms of various inflammatory diseases and cancer. In women, breast cancer is one of the most common diseases and numerous women succumb to it. The present study was undertaken to investigate the mechanism responsible for the SBGE­induced apoptosis of MCF­7 human breast cancer cells. SBGE was administered to cells at concentrations between 100 and 500 mg/ml, and cell viabilities were identified using an MTT assay. B­cell lymphoma 2 (Bcl-2) and Bcl-2 X­associated protein (Bax) family members were identified by western blotting, and the mRNA expression levels of the pro­apoptosis genes Fas, Fas ligand (FasL) and tumor necrosis factor (TNF)­α were assessed by reverse transcription­polymerase chain reaction. It was identified that SBGE treatment for 24 h inhibited MCF­7 proliferation and increased the sub­G1 phase ratio. SBGE suppressed mitochondrial membrane potentials and SBGE­induced apoptotic cell death was identified to be associated with downregulation of Bcl­2, but upregulation of Bax. SBGE­activated caspases 3 and 9, and increased reactive oxygen species generation. However, SBGE had no effect on the expression levels of Fas, FasL or TNF­α. Furthermore, mitogen­activated protein kinase and C­Jun N­terminal kinase inhibitors inhibited SBGE­induced cell death. These results suggested that SBGE be considered as an agent for the treatment of breast cancer.

Inhibition of lung cancer growth by HangAmDan-B is mediated by macrophage activation to M1 subtype.

Re-education of tumor-associated macrophages (TAMs) toward antitumor effectors may be a promising therapeutic strategy for the successful treatment of cancer. HangAmDan-B (HAD-B), a herbal formula, has been used for stimulating immune function and activation of vital energy to cancer patients in traditional Korean Medicine. Previous studies have reported the anti-angiogenic and anti-metastatic effects of HAD-B; however, evidence on the immunomodulatory action of HAD-B was not demonstrated. In the present study, immunocompetent mice were used to demonstrate the suppression of the in vivo growth of allograft Lewis lung carcinoma (LLC) cells, by HAD-B. In addition, HAD-B inhibited the in vitro growth of LLC cells by driving macrophages toward M1 polarization, but not through direct inhibition of tumor cell growth. Furthermore, culture media transfer of HAD-B-treated macrophages induced apoptosis of LLC cells. Results of the present study suggest that the antitumor effect of HAD-B may be explained by stimulating the antitumor function of macrophages. Considering the importance of re-educating TAMs in the regulation of the tumor microenvironment, the present study may confer another option for anti-cancer therapeutic strategy, using herbal medicines such as HAD-B.