Anticancer effects of genistein, green tea catechins, and cordycepin on oral squamous cell carcinoma

Oral squamous cell carcinoma (OSCC) is the most frequent form of oral cancer and holds the eighth position in the cancer incidence ranking. OSCC patients are treated by classical therapeutic modalities consisting of surgery, radiotherapy, and/or chemotherapy. But OSCC still shows significant mortality rates. Thus, new therapeutic approaches have been investigated and the most promising one is naturally acquired agents with known anti-cancer effects. Genistein is a compound extracted from soy bean. Its anti-cancer effect on breast cancer is well established now and it is investigated whether it has similar effect on OSCC. It inhibited the growth and invasiveness of OSCC cells in vitro, but these effects did not work in living animals in vivo. Catechin is a compound from green tea and its anti-cancer effect on OSCC is known better than other agents. Catechin showed its anti-cancer effect in vitro via induction of apoptosis, cell cycle arrest, inhibition of growth, and down-regulation of invasion/metastasis. These effects were confirmed in vivo with mouse model. Cordycepin is one of major pharmacologically important components in Cordyceps Militaris and may exert its anti-cancer effect as an adenosine receptor agonist. In recent study, it inhibited the proliferation of OSCC cells via A3 adenosine receptor. But because there is very scarce evidence on this effect, more researches are needed on this theme.

Survivin, Possible Marker and Prognostic Factor in Oral Squamous Cell Carcinomas

Survivin is a member of the inhibitors of apoptosis (IAP) family that have been known to inhibit activated caspases in apoptosis. In contrast to most IAP family members, survivin mRNA is expressed during fetal development, is not found in normal adult tissues and is overexpressed again in the cancer. Though survivin expression has been documented in most human cancers, little is known about its expression in OSCC and its potential value as a predictor of cancer survival. The purpose of this study was to investigate survivin expression in OSCC and to evaluate its value as a prognostic marker. We evaluated survivin expressions in cancer lines and OSCC samples and investigated the relationships between survivin expressions and clinico-pathological parameters including stage, differentiation, proliferation, lymph node metastasis, blood vessel density, and gelatinolytic activity. With immunohistochemistry, we analyzed survivin expression in 38 OSCCs. Patients' clinico-pathological parameters and their survival rate were analyzed to reveal their correlations with Survivin expressions. We cultured oral cancer cell lines and evaluated the correlation between gelatinolytic activities and survivin expressions of them. Survivin protein was observed both in nuclei and cytoplasm of tumor specimens while little or not observed in normal gingival mucosal tissues. Additionally, survivin expressions were correlated with lymph node metastasis, tumor proliferation and survival rate. Survivin expression was observed in 100% of 38 samples of OSCC and its expression levels are statistically associated with the proliferative activity of the tumors, lymph node metastasis and the survival of the patients. Based on these results, survivin is commonly expressed in OSCC and may thus provide valuable prognostic information related with lymph node metastasis, proliferation and survival rate as well as a potential therapeutic target in OSCC.

Effect of Docosahexaenoic Acid (DHA) on the Apoptosis of Human Endothelial ECV304 Cells

DHA, one of w-3 fatty acids, modulates cell growth or death though the changes of apoptotic signaling in human endothelial ECV304 cells. We investigated the effects of DHA on the changes of apoptotic signaling in human vascular endothelial ECV304 cells using lipid peroxidation (LPO) metabolites. LPO could be originated by dietary polyunsaturated fatty acids such as linoleic acid (LA), arachidonic acid (AA) and docosahexaenoic acid (DHA). DHA caused cell death of ECV304 cells compared to LA, AA or control as evidenced by changes in cell morphology and MTT assay. LPO levels was significantly elevated by 10 fold in DHA-treated ECV 304 cells and caspase-3 activity was increased by DHA corresponding to increasing incubation times compared to control. One of reasons of the cell death in DHA-treated ECV304 cells could be expected that caspase activity, marker for mitochondrial damages, might be triggered by the increasing LPO levels. Our results strongly indicated that DHA induced LPO production has an important role on apoptotic signaling pathway in ECV304 cells. LPO production in endothelial cells which was metabolized by oxidation of dietary PUFA, might be one of risk factors in the initial progression of atherosclerosis.

Chemopreventive effect of genistein in hamster buccal pouch carcinogenesis

Recently, the consumption of soy products has been associated with low rates of hormone-dependent and hormone-independent cancers. Asians, who consume 20~50times more soy per capita than Americans, have lower incidence and death rates from breast and prostate cancer. Because soy contains the isoflavones genistein and daidzein (present as their glycosidic conjugates) at mg/g concentrations, it has been suggested that isoflavones might be acting as natural chemopreventive agents. During the 1980s several groups of investigators carried out experiments to test the effectiveness of soy in the diet in animal models of cancer. These studies reported a protective effect of soy; none showed that soy increased cancer risk. Genistein was shown to inhibit the growth of a wide variety of tumor cell types in culture. The purpose of this study was to evaluate the effects of genistein on the carcinogenesis induced by topical application of 0.5% 9, 10-dimethyl 1,2-benzanthracene (DMBA) on the hamster buccal pouch. 48 syrian hamsters were employed in this study, divided into experimental group and control. 24 animals (DMBA topical application group) had the right buccal pouch painted 3times weekly with 0.5% DMBA in mineral oil, 24 animals (genistein group) were supplied with 0.1mg genistein with DMBA topical application. 3 animals in the experimental group and control were sacrificed at serially each other week after experiments. Their buccal pouches were removed and routinely processed for microscopic examination. The results were as follows: 1. In DMBA topical application and genistein group, they showed carcinogenesis as time goes by experimental stage. 2. Genistein group was retarded in carcinogenesis related to the acanthosis, hyperkeratosis, epithelial dysplasia. 3. p53 immunohistochemical study showed that the p53 protein of genistein group was less expressed than that of the control group. Thus, it seems that genistein has chemopreventive effect on the carcinogenesis in the oral cavity, but further study is required to elucidate the anticancer mechanism of genistein.