Advanced Pharmaceutical Bulletin
Volume:4 Issue: 5, Dec 2014

The aim of this article is to emphasize and focus on the preclinical and clinical update on phytochemicals and their role in prevention of oral carcinogenesis. Accordingly, the literature search was made following database: Embase, Medline, Science Citation index, NIH public access, pubmed and Cochrane Database of systematic reviews. Several internet websites were also searched to access publications from major phytochemical research sites and relevant information was obtained with regards to each plant chemical. The authors also spotted different list servers through wignet.com, Stanford cancer research etc: The data base search was made from the inception to 1988 and updated till 2013. A systematic method was obtained for literature search and data collection was critiqued. 60 articles were searched, among which there were only 6 systematic reviews on phytochemicals regarding oral carcinogenesis. Additional articles were obtained on phytochemicals and their mechanism of action in other cancers, which were regarded as background material. The studies done by various authors on each phytochemical has been briefly emphasized.

Cancer is uncontrolled growth of abnormal cells in the body. Nowadays, cancer is considered as a human tragedy and one of the most prevalent diseases in the wide, and its mortality resulting from cancer is being increased. It seems necessary to identify new strategies to prevent and treat such a deadly disease. Control survival and death of cancerous cell are important strategies in the management and therapy of cancer. Anticancer agents should kill the cancerous cell with the minimal side effect on normal cells that is possible through the induction of apoptosis. Apoptosis is known as programmed cell death in both normal and damaged tissues. This process includes some morphologically changes in cells such as rapid condensation and budding of the cell, formation of membrane-enclosed apoptotic bodies with well-preserved organelles. Induction of apoptosis is one of the most important markers of cytotoxic antitumor agents. Some natural compounds including plants induce apoptotic pathways that are blocked in cancer cells through various mechanisms in cancer cells. Multiple surveys reported that people with cancer commonly use herbs or herbal products. Vinca Alkaloids, Texans, podo phyllotoxin, Camptothecins have been clinically used as Plant derived anticancer agents. The present review summarizes the literature published so far regarding herbal medicine used as inducers of apoptosis in cancer.

The antitumor activity of Kielmeyera coriacea (Clusiaceae), a medicinal plant used in the treatment of parasitic, as well as fungal and bacterial infections by the Brazilian Cerrado population, was investigated. A chloroform extract (CE) of K. coriacea was tested in the murine melanoma cell line (B16F10-Nex2) and a panel of human tumor cell lines. Tumor cell migration was determined by the wound-healing assay and the in vivo antitumor activity of CE was investigated in a melanoma cell metastatic model. 1H NMR and GC/MS were used to determine CE chemical composition. We found that CE exhibited strong cytotoxic activity against murine melanoma cells and a panel of human tumor cell lines in vitro. CE also inhibited growth of B16F10-Nex2 cells at sub lethal concentrations, inducing cell cycle arrest at S phase, and inhibition of tumor cell migration. Most importantly, administration of CE significantly reduced the number of melanoma metastatic nodules in vivo. Chemical analysis of CE indicated the presence of the long chain fatty compounds, 1-eicosanol, 1-docosanol, and 2-nonadecanone as main constituents. These results indicate that K. coriacea is a promising medicinal plant in cancer therapy exhibiting antitumor activity both in vitro and in vivo against different tumor cell lines.

Accumulating evidence indicates that glycyrrhizin (GZ) and its hydrolyzed metabolite 18-β glycyrrhetinic acid (GA) exhibit anti-inflammatory and anticancer activities. The objective of this study was to examine the in vitro cytotoxic activity of GA on human ovarian cancer A2780 cells. A2780 cells were cultured in RPMI1640 containing 10% fetal bovine serum. Cells were treated with different doses of GA and cell viability and proliferation were detected by dye exclusion and 3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) assays. Apoptosis induction and expression of Fas and Fas ligand (FasL) were analyzed by flow cytometry. We observed that GA decreases cell viability and suppressed cells proliferation in a dose-dependent manner as detected by dye-exclusion and XTT assayes. In addition, our flow cytometry data show that GA not only induces apoptosis in A2780 cells but also upregulates both Fas and FasL on these cells in a dose-dependent manner. we demonstrate that GA causes cell death in A2780 cells by inducing apoptosis.

The main purpose of this study was to investigate the protective role of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced oxidative damage in erythrocyte during aging in humans. Human erythrocyte membrane bound Ca2+-ATPase and Na+/K+-ATPase activities were determined as a function of human age. Protective role of epigallocatechin-3-gallate was evaluated by in vitro experiments by adding epigallocatechin-3-gallate in concentration dependent manner (final concentration range 10-7M to 10-4M) to the enzyme assay medium. Oxidative stress was induced in vitro by incubating washed erythrocyte ghosts with tertiary butyl hydroperoxide (10-5 M final concentration). We have reported concentration dependent effect of epigallocatechin-3-gallate on tertiary butyl hydroperoxide induced damage on activities of Ca2+-ATPase and Na+/K+-ATPase during aging in humans. We have detected a significant (p < 0.001) decreased activity of Ca2+-ATPase and Na+/K+ -ATPase as a function of human age. Epigallocatechin-3-gallate protected ATPases against tertiary butyl hydroperoxide induced damage in concentration dependent manner during aging in humans. Epigallocatechin-3-gallate is a powerful antioxidant that is capable of protecting erythrocyte Ca2+-ATPase and Na+/K+ -ATPase against oxidative stress during aging in humans. We may propose hypothesis that a high intake of catechin rich diet may provide some protection against development of aging and age related diseases.

The aim of present study was to determine effects of L-Arginine supplementation on antioxidant status and body composition in obese patients with prediabetes. A double-blind randomized control trial was performed on 46 (24 men, 22 women) obese patients with prediabetes. They were divided randomly into two groups. Patients in intervention (n = 23) and control group (n=23) received 3 gr/day L-arginine and placebo, respectively for 8 weeks. Anthropometric indices, dietary intake and biochemical measurements ((serum total antioxidant capacity (TAC), Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD)) were performed at the baseline and after 8-week intervention. The mean age and BMI of participants were 44.29±8.65 years old and 28.14±1.35 kg/m2, respectively. At the end of study, in both intervention and control group, percentage of carbohydrate decreased and %fat intake increased compared to the baseline (P<0.05). After adjusting for dietary intake, no significant difference was observed in Fat Mass (FM) and Fat Free Mass (FFM) between two groups (P>0.05). Among measured biochemical factors, only serum TAC level showed significant differences at the end of study in the intervention group compared to the control group (pv<0.01). 3gr/day L-Arginine supplementation increased TAC level in obese patients with prediabetes.

The aim of present study was to determine effects of L-Arginine supplementation on antioxidant status and body composition in obese patients with prediabetes. A double-blind randomized control trial was performed on 46 (24 men, 22 women) obese patients with prediabetes. They were divided randomly into two groups. Patients in intervention (n = 23) and control group (n=23) received 3 gr/day L-arginine and placebo, respectively for 8 weeks. Anthropometric indices, dietary intake and biochemical measurements ((serum total antioxidant capacity (TAC), Glutathione Peroxidase (GPx) and Superoxide Dismutase (SOD)) were performed at the baseline and after 8-week intervention. The mean age and BMI of participants were 44.29±8.65 years old and 28.14±1.35 kg/m2, respectively. At the end of study, in both intervention and control group, percentage of carbohydrate decreased and %fat intake increased compared to the baseline (P<0.05). After adjusting for dietary intake, no significant difference was observed in Fat Mass (FM) and Fat Free Mass (FFM) between two groups (P>0.05). Among measured biochemical factors, only serum TAC level showed significant differences at the end of study in the intervention group compared to the control group (pv<0.01). 3gr/day L-Arginine supplementation increased TAC level in obese patients with prediabetes.

Naturally occurring substances as novel drugs in cancer therapy, at all times, represent a challenge to science since medicinal plants are proving to be brilliant sources of new chemopreventive agents. In the present study, methanol extract from aerial parts of Marrubium crassidens was assessed for its antiproliferative activity in the breast cancer cell line MCF-7 through MTT bioassay using cell viability and cytotoxicity indices. The antioxidant property of M. crassidens extract together with its phenolic and flavonoids content were evaluated, as well. According to data obtained in the study, M. crassidens exhibited antiproliferative activity with a gradual rise in cytotoxicty effect setting out on 240µg/mL concentration of the extract. Moreover, the RC50 value for antioxidant activity of the extract was determined as 40µg/mL and values for the total phenolic and flavonoids were calculated as 512.64mg gallic acid equivalent and 212.73mg quercetin equivalent per 100g of dry plant material. Generally, the observed antiproliferative and antioxidant properties of M. crassidens could be certified to the high amounts of phenolic and flavonoid content detected in the extract.

Despite significant advances have been achieved in cancer therapy, response to conventional treatments like surgery, radiotherapy and chemotherapy varies among individuals. Immunotherapy is known to be an effective strategy for patients who are resistant to the currently available interventions. Ninety-six male Balb/c mice (aged 6-8 weeks) were selected and divided into twelve groups of eight. Approximately, 1×106of WEHI-164 cells were injected to each mouse for tumor genesis. Five immunotherapy treatments were considered in this study, including Heat Shock Proteins (HSP), Bacillus Calmette-Guérin (BCG), Bifidobacterium, Immuno-Modulator Drug (IMOD) and Thalidomide. After tumor formation, the groups were treated with one or more of these therapies. Tumor size and survival rate was regularly monitored. Depending on the treatment group, tumor sizes were different. In some groups, combined treatments demonstrated more inhibitory effects on tumor growth rate. The mice in group (IMOD+ Thalidomide) had the lowest survival rate but group (BCG+ HSP+ Thalidomide) survived until the end of the experiment. The (HSP+ BCG+ Thalidomide) group exhibited satisfactory outcomes and two third of the mice in this group went into complete remission. Some combination therapies in test groups had significant impacts on survival and tumor growth rate.

Breast cancer is the most common female malignancy in the world. Beta glucan may improve quality of life in cancer patients receiving chemotherapy. The aim of this trial was to determine the effect of Beta glucan on quality of life in women with breast cancer undergoing chemotherapy. This study was conducted on 30 women with breast carcinoma. The eligible participants were randomly assigned to intervention (n=15) or placebo (n=15) groups using a block randomization procedure. Patients in the intervention group received two 10-mg capsules of soluble 1–3, 1–6, D-beta glucan daily and the placebo group received placebo for 21 days, in an interval between two courses of chemotherapy. Health - related quality of life (HRQL) was evaluated using the EORTC Quality of Life Questionnaire version.3.0 (EORTC QLQ-C30) at the beginning and end of the study. At the end of the study, the Global health status /QoL score for the Beta glucan group was significantly increased (P=0.023), but the difference between the two groups was not significant. After intervention, the Functional scales score showed no significant change (P=0.099) between the two groups or within the groups. At the end of the study, the Symptom scales\items score was decreased significantly in Beta glucan group comparing the placebo group (P=0.048), as well as after adjusting for baseline score. The Symptom scales\items score’s change was significant (P=0.012) within the Beta glucan group, compared with the baseline score. The findings suggest that Beta glucan may be useful as a complementary or adjuvant therapy for improving quality of life in breast cancer patients in combination with cancer therapies.