Role of Vitamin E in Prevention of Breast Cancer: An Epidemiological Review

Breast cancer rates are so high among women in more developed countries, rates are increasing in almost every region of the world. In 2018, it is reported that 627,000 women died from breast cancer. Vitamin E is a common supplement characterized by its antioxidant potential effects on many chronic conditions that prevent free radicals from harming DNA, protein and cell membranes may serve as a part of cancer growth by reducing oxidative DNA alteration. The major forms of vitamin E as an anticancer agent, which acts as major antioxidants to regulate peroxidation reactions and control free-radical production within the body, are tocopherols and tocotrienols. Since Vitamin E had first acted as a non-antioxidant, α-tocopherol has inhibited smooth muscle proliferation activity and protein kinase C activity. Although tocotrienols are mostly investigated as antioxidant effects of tocotrienol, which plays an important role in reducing the damage to DNA by decreasing the by-product of lipid peroxidation. This study aims to investigate the connection between vitamin E and also the risk of breast cancer and the outcome is that some inverse relationship between vitamin E and breast cancer exists. There has been clear evidence that vitamin E reduces the risk of human cancer but our main focus is on breast cancer, seen in many prospective and retrospective case-control, cohort and intervention studies.

Not so dry after all – DRY mutants of the AT1A receptor and H1 receptor can induce G protein-dependent signaling

ABSTRACTGPCRs are seven transmembrane spanning receptors that regulate a wide array of intracellular signaling cascades in response to various stimuli. To do so, they couple to different heterotrimeric G proteins and adaptor proteins, including arrestins. Importantly, arrestins were shown to regulate GPCR signaling through G proteins, as well as promote G protein-independent signaling events. Several research groups have reported successful isolation of exclusively G protein-dependent and arrestin-dependent signaling downstream of GPCR activation using biased agonists or receptor mutants incapable of coupling to either arrestins or G proteins. In the latter category, the DRY mutant of the angiotensin II type 1 receptor was extensively used to characterize functional selectivity downstream of AT1AR. In an attempt to understand histamine 1 receptor signaling, we characterized the signaling capacity of the H1R DRY mutant in a panel of dynamic, live cell biosensor assays, including arrestin recruitment, heterotrimeric G-protein activation, Ca2+ signaling, protein kinase C activity, GTP binding of RhoA, and activation of ERK1/2. Here we show that both H1R DRY mutant and the AT1AR DRY mutant (used as a reference) are capable of efficient activation of G protein-mediated signaling. Therefore, contrary to common belief, they do not constitute suitable tools for dissection of arrestin-mediated, G protein-independent signaling downstream of these receptors.

Lycopene depresses glutamate release through inhibition of voltage-dependent Ca2+ entry and protein kinase C in rat cerebrocortical nerve terminals

Lycopene is a natural dietary carotenoid that was reported to exhibit a neuroprotective profile. Considering that excitotoxicity and cell death induced by glutamate are involved in many brain disorders, the effect of lycopene on glutamate release in rat cerebrocortical nerve terminals and the possible mechanism involved in such effect was investigated. We observed here that lycopene inhibited 4-aminopyridine (4-AP)-evoked glutamate release and intrasynaptosomal Ca2+ concentration elevation. The inhibitory effect of lycopene on 4-AP-evoked glutamate release was markedly reduced in the presence of the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channel blocker ω-conotoxin MVIIC, but was insensitive to the intracellular Ca2+-release inhibitors dantrolene and CGP37157. Furthermore, in the presence of the protein kinase C inhibitors GF109203X and Go6976, the action of lycopene on evoked glutamate release was prevented. These results are the first to suggest that lycopene inhibits glutamate release from rat cortical synaptosomes by suppressing presynaptic Ca2+ entry and protein kinase C activity.