Cancer Chemoprevention & Herbal Antioxidants 85 promotion. This process is generally characterized by two important cellular events viz., cellular proliferation and apoptosis. Cellular proliferation, under normal conditions is a well regulated process where proliferation signals interplay with cell cycle checkpoint proteins. However, in transformed cells these regulatory processes are over-ridden to cause hyper proliferation under the influence of certain promotion signals like stress etc. Proliferation can be initiated by different endogenous and exogenous signals like mitogenic stimuli like growth factors, oxidative stress and hormones. Irrespective of the stimuli certain cellular pathways and down stream events remain similar in number of tissues and cell types. Few of such bio-molecules or effectors are protein kinase C (PKC family of proteins), PI3Kinase, MAP kinases like erk, jnk, p38 etc. These kinases upon activation upregulate a number of transcription factors like jun, fos, Nuclear factor kappa B (NF-kB), c-myc etc. that in turn regulate cell pro- liferation [9]. Thus, agents which can decrease activation of these signaling molecules can suppress the proliferation and hence promotion. Such agents are generally termed as suppressors. Another important cellular event exploited in chemo- prevention is apoptosis, which is characterized by cell shrinkage, membrane blebbing, chromatin condensation and DNA fragmentation. Induction of apoptosis or cell cycle arrest by elimination of cells under stress or genetically damaged cells may represent a protective mechanism by which chemopreventive agents can inhibit promotion/pro- gression stages of carcinogenesis. General mechanisms for induction of apoptosis are hypothesized to be via stress signals elicited by chemopreventive agents that lead to the loss of mitochondrial membrane potential followed by release of cytochrome c. Consequently, an apoptosome is formed by the cytochrome c, apoptotic protease activating factor-1 (APAF-1) and caspase 9, which later results into activation of downstream effector caspases [10]. Loss of mitochondrial membrane potential is also inhibited by Bcl2 (anti-apoptotic protein) or induced by Bax (proapoptotic protein). Further- more, dietary agent induced activation of p53 (activator of bax) can also mediate apoptosis in response to DNA damage [11]. Hence, chemopreventive agents can alter the trigger for apoptosis by altering the expression of anti/pro- apoptotic proteins, which in turn regulate mitochondrial membrane potential and caspase activation. Chemopreventive antioxidants can also induce apoptosis by modulating acti- vation of certain transcription factors such as NF-kB and AP1 family members which are involved in induction of cell survival genes (Fig. 4). Herbal Compounds as Chemopreventive Agents Among various chemopreventive compounds, dietary agents, due to their high tolerability and low toxicity are Vol. 40, No. 2, 2007 Fig. 4. Schematic presentations of signaling cascade where chemopreventive agents act as a suppressor. Chemopre- ventive agent can act as a suppressor either by inhibiting signaling kinases that activate transcription factor like AP-1 and NF-kB which in turn activate cell proliferation genes or by inducing apoptosis via activation of proapo- ptotic proteins like bax. C = chemopreventive agent; wt = wild type. fast becoming lucrative targets. Based on experimental and epidemiological evidences, chemoprevention or dietary intervention especially employing herbal anti-oxidants is receiving increasing attention as they have shown anti- initiating and/or anti-promoting activities in experimental systems [4]. Tabulated below is a partial list of plants reported to possess chemopreventive potential along with probable active component(s) and their mode(s) of action (Table 1). Few of the compounds like epigallocatechin gallate (green tea catechin), curcumin, indole-3-carbinol, resvera- trol, etc. mentioned in Table 1 are currently undergoing clin- ical trials [12]. Of the many chemopreventive agents listed in the Table 1, we have focused our studies on turmeric and black tea. Studies on Chemopreventive Efficacies of Turmeric The powdered rhizome of the plant Curcuma longa known as turmeric has number of medicinal properties. Studies in our lab have shown turmeric and its active