Pleiotrophic effects of natural products in ROS-induced carcinogenesis: the role of plant-derived natural products in oral cancer chemoprevention.

Cancer is a multistage process where each stage involves different molecular, biochemical and cellular events all of which, however, contribute to malignant transformation. Over the last years, substantial scientific evidence has promoted the hypothesis that ROS-induced cellular damage underlies key steps during development of the malignant phenotype including evasion of apoptosis, limitless proliferation, angiogenesis, tissue invasion and metastasis, etc. On the other hand, natural products hold great promise as anti-cancer compounds in preventing against carcinogenesis both in vitro and in vivo. Throughout this article, we aim to review the evidence as to how some of these natural products exert their chemopreventive effects in human carcinogenesis. For this reason, we have placed particular emphasis on oral cancer where significant efforts have been made in alternative therapeutic strategies such as the use of plant-derived natural products. This is of paramount importance given the disease's high morbidity and mortality rates across the world and specifically in the geographic regions of India and South-East Asia where its incidence is increasing.

Autocrine signaling involved in cell volume regulation: the role of released transmitters and plasma membrane receptors.

Cell volume regulation is a basic homeostatic mechanism transcendental for the normal physiology and function of cells. It is mediated principally by the activation of osmolyte transport pathways that result in net changes in solute concentration that counteract cell volume challenges in its constancy. This process has been described to be regulated by a complex assortment of intracellular signal transduction cascades. Recently, several studies have demonstrated that alterations in cell volume induce the release of a wide variety of transmitters including hormones, ATP and neurotransmitters, which have been proposed to act as extracellular signals that regulate the activation of cell volume regulatory mechanisms. In addition, changes in cell volume have also been reported to activate plasma membrane receptors (including tyrosine kinase receptors, G-protein coupled receptors and integrins) that have been demonstrated to participate in the regulatory process of cell volume. In this review, we summarize recent studies about the role of changes in cell volume in the regulation of transmitter release as well as in the activation of plasma membrane receptors and their further implications in the regulation of the signaling machinery that regulates the activation of osmolyte flux pathways. We propose that the autocrine regulation of Ca2+-dependent and tyrosine phosphorylation-dependent signaling pathways by the activation of plasma membrane receptors and swelling-induced transmitter release is necessary for the activation/regulation of osmolyte efflux pathways and cell volume recovery. Furthermore, we emphasize the importance of studying these extrinsic signals because of their significance in the understanding of the physiology of cell volume regulation and its role in cell biology in vivo, where the constraint of the extracellular space might enhance the autocrine or even paracrine signaling induced by these released transmitters.