Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with poor outcome. Because of lacking therapeutic targets, chemotherapy is the main treatment option for patients with TNBC. Overexpression of HDACs correlates with tumorigenesis, highlighting the potential of HDACs as therapeutic targets for TNBC. Here we demonstrate that trichostatin A (TSA, a HDAC inhibitor) selectively inhibits the proliferation of TNBC cell lines HCC1806 and HCC38 rather than a normal breast cell line MCF10A. The inhibition of TNBC by TSA is via its roles in inducing cell cycle arrest and apoptosis. TSA treatment leads to decreased expression of CYCLIN D1, CDK4, CDK6 and BCL-XL, but increased P21 expression. Moreover, combination of TSA with doxorubicin has synergistic effects on inhibiting proliferation of HCC1806 and HCC38 cells. Our studies identified a promising epigenetic-based therapeutic strategy that may be implemented in the therapy of fatal human breast cancer.

Quercetin-3-O-α-L-rhamnopyranoside (QI) is derived from the leaves of Lindera aggregata (Sims) Kosterm. And exhibits multiple biological activities, including an antioxidant activity. However, the detailed molecular mechanism of its antioxidant activity remains unknown. The aim of the present study was to investigate the antioxidant activity of QI and the underlying molecular mechanism in human umbilical vein endothelial cells (HUVEcs). An oxidative stress model was established in HUVEcs using H 2 O 2 , and cells were then treated with different concentrations of QI. The results revealed that the exposure of HUVEcs to QI protected these cells from H 2 O 2-induced damage. QI treatment also increased the activities of the antioxidant enzymes superoxide dismutase (SOd) and glutathione (GSH) in the cell culture medium. In addition, QI inhibited H 2 O 2-induced apoptosis by decreasing the expression levels of cleaved caspase-9 and poly(AdP-ribose) polymerase. QI also inhibited the production of dNA fragments and reactive oxygen species induced by H 2 O 2. Furthermore, QI decreased the oxidative stress by promoting the nuclear transfer of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 by activating autophagy, and inhibited the competition of Bach1 from Nrf2. Finally, QI significantly improved the activities of T-SOD and GSH, and decreased the content of malondialdehyde in the serum and heart tissue of aging rats. These data support the use of QI as a health supplement to alleviate oxidative stress or further development of this compound as an antioxidant drug.

Promotion of cytoplasmic vacuolation-mediated cell death of human prostate cancer PC-3 cells by oxidative stress induced by daucusol, a new guaianetype sesquiterpenoid from Daucus carota L. Arch Biol Sci. 2017;69(3):481-9.Abstract: We investigated the antitumor activity of daucusol (DS) derived from Daucus carota L. in PC-3, A549 and HeLa cell lines by the MTT assay. Optical microscopy revealed that exposure of PC-3 cells to DS resulted in cytoplasmic vacuolation. Flow cytometry analysis of the phase of the cell cycle did not reveal a sub-G1 peak, and no caspase-dependent activation was observed after DS treatment. The levels of endoplasmic reticulum (ER) stress biomarkers, LC3B-II and ubiquitinated proteins were increased. It was also observed that oxidative stress played an important role in the activation of the cytoplasmic vacuolation-mediated cell-death pathway. In vivo, DS inhibited tumor growth in nude mice by 39.13% compared to the vehicle. Protein expression in the tumor tissue was consistent with their expression in vitro. Our findings indicate that DS induced cytoplasmic vacuolation-mediated death in PC-3 cells by triggering oxidative stress and suggest that targeting this pathway could serve as a novel therapeutic approach for prostate cancer.

To investigate the effect of phospholipid transfer protein (PLTP) on the cigarette smoke extract (CSE)-induced production of interleukin-8 (IL-8) in human pulmonary epithelial cells, male Wistar rats were exposed to air and cigarette smoke (n = 10/exposure) for 6 h/day on three consecutive days. Their lungs were sectioned and bronchoalveolar lavage fluid (BALF) examined. The expression of PLTP and IL-8 in the lung was detected immunohistochemically. Lung injury was accompanied by the upregulation of PLTP and IL-8 in the CSE-exposed rat model, and the number of white blood cells in the BALF was significantly increased compared with those of the controls. Both neutrophils and macrophages were clearly increased. Human alveolar epithelial cells (A549) and human bronchial epithelial cells (HBECs) were treated with different concentrations of CSE for various times. The cells were also transfected with small interfering RNA directed against PLTP, and U0126, an inhibitor of the ERK1/2 pathway, was administered before CSE exposure. The expression of PLTP and IL-8 mRNAs and PLTP, IL-8, total ERK, and phosphorylated ERK proteins was analyzed. The expression of IL-8 and phosphorylated ERK was significantly increased in A549 cells and HBECs after CSE stimulation, and CSE upregulated the expression of PLTP in A549 cells. In contrast, CSE inhibited the expression of PLTP in HBECs. The CSE-induced expression of IL-8 and p-ERK was significantly increased by the knockdown of PLTP. Therefore, PLTP may regulate CSE-induced IL-8 expression via the ERK1/2 signaling pathway in human pulmonary epithelial cells.