Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitation and hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.

Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention

Chemoprevention, a relatively new and promising strategy to prevent cancer, is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the process of carcinogenesis. The chemopreventive effects elicited by these natural dietary compounds are believed to include antioxidative, anti-inflammatory activity, induction of phase II enzymes, apoptosis, and cell cycle arrest. Many mechanisms have been shown to account for the anticarcinogenic actions of natural dietary compounds; attention has recently been focused on intracellular-signaling cascades as common molecular targets for various chemopreventive natural dietary compounds. In this critical review, we will summarize current knowledge on natural dietary compounds that act through the signaling pathways and modulate gene expression to induce detoxifying enzymes, programmed cell death, anti-inflammatory, and anti-proliferative effects, thus providing evidence for these substances in cancer chemopreventive action (128 references).

Chemopreventive effects of natural dietary compounds on cancer development

http://ir.lib.isu.edu.tw/bitstream/987654321/10816/1/10816-1.PDF

Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells.

Cancer chemoprevention with garlic and its constituents

Purpose: Cyclooxygenase-2 (COX-2) inhibitors hold promise for cancer chemoprevention; however, recent toxicity concerns suggest that new strategies are needed. One approach to overcome this limitation is to use lower doses of COX-2 inhibitors in combination with other established agents with complementary mechanisms. In this study, the effect of (−)epigallocatechin-3-gallate (EGCG), a promising chemopreventive agent from green tea, was tested alone and in combination with specific COX-2 inhibitors on the growth of human prostate cancer cells both in vitro and in vivo . Experimental Design: Human prostate cancer cells LNCaP, PC-3, and CWR22Rν1 were treated with EGCG and NS398 alone and in combination, and their effect on growth and apoptosis was evaluated. In vivo , athymic nude mice implanted with androgen-sensitive CWR22Rν1 cells were given green tea polyphenols (0.1% in drinking water) and celecoxib (5 mg/kg, i.p., daily, 5 days per week), alone and in combination, and their effect on tumor growth was evaluated. Results: Combination of EGCG (10-40 μmol/L) and NS-398 (10 μmol/L) resulted in enhanced ( a ) cell growth inhibition; ( b ) apoptosis induction; ( c ) expression of Bax, pro-caspase-6, and pro-caspase-9, and poly(ADP)ribose polymerase cleavage; ( d ) inhibition of peroxisome proliferator activated receptor γ; and ( e ) inhibition of nuclear factor-κB compared with the additive effects of the two agents alone, suggesting a possible synergism. In vivo , combination treatment with green tea polyphenols and celecoxib resulted in enhanced ( a ) tumor growth inhibition, ( b ) lowering of prostate-specific antigen levels, ( c ) lowering of insulin-like growth factor-I levels, and ( d ) circulating levels of serum insulin-like growth factor binding protein-3 compared with results of single-agent treatment. Conclusions: These data suggest synergistic and/or additive effects of combinatorial chemopreventive agents and underscore the need for rational design of human clinical trials.

https://clincancerres.aacrjournals.org/content/clincanres/13/5/1611.full.pdf

Combined Inhibitory Effects of Green Tea Polyphenols and Selective Cyclooxygenase-2 Inhibitors on the Growth of Human Prostate Cancer Cells Both In vitro and In vivo

Combination chemoprevention by diet-derived agents that induce apoptosis is a promising strategy to control gastric cancer, the second most common malignancy worldwide. The present study was undertaken to investigate the apoptosis-inducing potential of a combination of S-allylcysteine (SAC), an organosulphur constituent of garlic and lycopene, a tomato carotenoid during N-methyl-N'-nitro-N-nitroso-guanidine (MNNG) and saturated sodium chloride (S-NaCl)-induced gastric carcinogenesis in Wistar rats using the apoptosis-associated proteins Bcl-2, Bax, Bim, caspase 8 and caspase 3 as markers. Animals administered MNNG followed by S-NaCl developed squamous cell carcinomas of the stomach associated with increased Bcl-2 expression and decreased expression of Bax, Bim, caspase 8 and caspase 3. Although SAC and lycopene alone significantly suppressed the development of gastric cancer, administration of SAC and lycopene in combination was more effective in inhibiting MNNG-induced stomach tumours and modulating the expression of apoptosis-associated proteins. Our results suggest that induction of apoptosis by SAC and lycopene combination represents one of the possible mechanisms that could account for their synergistic chemopreventive activity against gastric cancer.

A Mani

Papers

Combination of S-allylcysteine and lycopene induces apoptosis by modulating Bcl-2, Bax, Bim and caspases during experimental gastric carcinogenesis