A-Tocopherol succinate (TS), an analogue of vitamin E, has growth-inhibitory activity in a wide spectrum of in vitro and in vivo cancer models. Here, we report that modulation of oncogenic Ras is associated with TS activity. TS inhibits the proliferation and induces apoptosis of NIH3T3 cells stably transfected with oncogenic K-Ras and H-Ras, but not NIH3T3 cells expressing empty vector. TS treatment resulted in decreased Ras protein levels in oncogenic Ras expressing NIH3T3 cells but not in parental NIH3T3 cells. Treatment with TS suppressed the levels of phospho-Akt and phospho-Erk1/2 in oncogenic Ras expressing NIH3T3 cells. Overexpression of constitutively active phosphoinositide-3-kinase, Akt, and Mek1/2 significantly attenuated TS growth inhibition of oncogenic Ras-transformed NIH3T3 mouse fibroblast cell lines. In addition, transcriptional targets of oncogenic Ras such as c-Myc, cyclin D1, and E2F1 were down-regulated by TS in oncogenic Ras-expressing cells. The above TS effects on oncogenic Ras signaling were also observed in endogenous oncogenic K-Ras expressing HCT 116 (human colon cancer) and MDA-MB-231 (human breast cancer) cells. Taken together, these data show that TS down-regulation of the Ras signaling pathways that are mediated by Mek/Erk and phosphoinositide-3-kinase/Akt plays, at least in part, a critical role in TS inhibition of proliferation and survival of transformed cells. This data supports further investigation of the chemopreventive and therapeutic potential of TS in tumors that are dependent on activated Ras signaling and identifies phosphor-Erk and phosphor-Akt as potential biomarkers of TS activity.

Veterinary profession sphere overlaps three major biology arenas namely agriculture, basic sciences, and human medicine. Thus, so far the investments in veterinary field are not proportional to the scope of their responsibilities. Rededication and rejuvenation can help veterinary profession to maximize outcomes in poverty alleviation, food security, environmental protection, integrated zoonotic disease prevention and control, integrated public services delivery, animal welfare and human-animal bond. Transforming backyard farming into farm management; symptomatic treatment philosophy into prevention and control ethos; one medicine, require capacity building, continuing education as well as curriculum reforms. Consensus needs to be built within the profession to enrol stakeholder participation in professional growth and outcomes enhancement. In this article, authors used developed world experience to suggest a customized reform and manpower empowerment approach for increasing veterinary profession stature and contributions for India. It is hoped that awareness brought forward to elevate discussion on veterinary profession opportunities would be beneficial to the profession as well as to the society.