The Opioid Growth Factor in Growth Regulation and Immune Responses in Cancer.

It has become apparent that endogenous opioids act not only as neurotransmitters and neuromodulators, but have multiple functions in the body. Activation of the opioid system by opiate drugs is associated with a risk of cancer development through direct stimulation of tumor cell proliferation and through immunosuppression. In contrast, the endogenous peptide opioid [Met5]-enkephalin, now commonly referred to as Opioid Growth Factor (OGF), negatively regulates cell proliferation in a wide number of cells during development, homeostasis, and neoplasia. This action is mediated through the opioid growth factor receptor, originally designated the zeta (ζ) opioid receptor. Further, contrary to the traditional notion of opiates as immunosuppressive, endogenous OGF has been shown to possess a number of positive immunomodulatory properties and may provide a beneficial effect in cancer by augmenting the activity of cells involved in both innate and acquired immunity. Taken together, the evidence supports consideration of opioid peptides such as OGF as new strategies for cancer therapy.

Effect of ghost pepper on cell proliferation, apoptosis, senescence and global proteomic profile in human renal adenocarcinoma cells.

Chili peppers are an important constituent of many foods and contain medicinally valuable compounds, such as capsaicin and dihydrocapsaicin. As various dietary botanicals have anticancer properties, this study was aimed to examine the effect of Ghost pepper (Bhut Jolokia), one of the hottest chili peppers in the world, on cell proliferation, apoptosis, senescence and the global proteomic profile in human renal cell adenocarcinoma in vitro. 769-P human renal adenocarcinoma cells were cultured on RPMI-1640 media supplemented with fetal bovine serum (10%) and antibiotic-antimycotic solution (1%). Treatment stock solutions were prepared in ethanol. Cell proliferation was tested with phenol red-free media with capsaicin (0-400 µM), dihydrocapsaicin (0-400 µM), capsaicin + dihydrocapsaicin (5:1), and dry Ghost peppers (0-3 g L-1) for 24, 48 and 72 h. Polycaspase and senescence associated-beta-galactosidase (SA-beta-gal) activities were tested with capsaicin (400 µM), dihydrocapsaicin (400 µM), capsaicin (400 µM) + dihydrocapsaicin (80 µM), and ghost pepper (3 g L-1) treatments. Global proteomic profile of cells in control and ghost pepper treatment (3 g L-1) was analyzed after 6 h by a shotgun proteomic approach using tandem mass spectrometry. At 24 h after treatment (24 HAT), relative to control, cell proportion with capsaicin (400 µM), dihydrocapsaicin (400 µM), capsaicin (400 µM) + dihydrocapsaicin (80 µM), and ghost pepper (3 g L-1) treatments was reduced to 36%, 18%, 33% and 20%, respectively, and further reduced at 48 and 72 HAT. All treatments triggered an early polycaspase response. SA-beta-gal activity was normal or suppressed with all treatments. About 68,220 protein isoforms were identified by shotgun proteomic approach. Among these, about 8.2% were significantly affected by ghost pepper. Ghost pepper regulated various proteins involved in intrinsic and extrinsic apoptotic pathways, Ras, Rb/E2F, p53, TGF-beta, WNT-beta catenin, and calcium induced cell death pathways. Ghost pepper also induced changes in proteins related to methylation, acetylation, genome stability, cell cycle check points, carbohydrate, protein and other metabolism and cellular mechanisms. Ghost pepper exhibited antiproliferation activity by inducing apoptosis through a complex network of proteins in human renal cell adenocarcinoma in vitro.

Shear stress activates Akt during vascular smooth muscle cell reorientation.

Vascular intervention procedures can lead to endothelial damage and expose the underlying VSMCs (vascular smooth muscle cells) to shear stress. Although shear stress has been implicated in the proliferation and migration of VSMCs, the molecular mechanism(s) underlying these events are not well understood. In the present study, we examined the effect of shear stress on VSMC reorientation and the activation of Akt (also called protein kinase B) pathway signalling. Cells were subjected to a shear of 9.8 dynes/cm2 (1 dyne=10-5 N) for 0 min, 5 min, 15 min, 30 min, 1 h, 4 h and 24 h. Shear stress caused the VSMCs to realign at an angle that was approximately 45 degrees relative to the shear force vector after 24 h. Immunoblotting demonstrated that the phosphorylations of Akt and Akt-related signalling proteins [mTOR (mammalian target of rapamycin), PTEN (phosphatase and tensin homologue deleted on chromosome 10) and p70S6k (p70 S6-kinase)] were increased after shear stimulation. These results indicate that the activation of the Akt pathway signalling is closely correlated with shear-induced VSMC reorientation.