Aspirin and ITS combinations as new chemopreventive strategies against cancer

Cancer has become one of the most common causes of death in industrialized countries and has been defined as the medical challenge of our times. The high aggressiveness and therapeutic resistance of some tumors have motivated the development of new strategies for their prevention and/or treatment. Chemoprevention, a relatively new and promising strategy to prevent cancer, is defined as the use of natural and/or synthetic substances to block, reverse, or retard the process of carcinogenesis. To achieve greater inhibitory effects on cancer cells, combinations of two or more chemotherapeutic agents are commonly considered as a better preventive and/or therapeutic strategy. Optimization of such combinations based on the elucidation of molecular mechanisms may result in an increased tumor response and reduction of toxicity in normal cells. Aspirin (acetylsalicylic acid) and other non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cycloxygenase (COX) enzyme, reducing inflammation associated to several types of cancer, such as colorectal, breast, lung, prostate, esophagus, stomach and ovary cancers. Moreover, epidemiological evidence suggests a promising chemo-preventive role of aspirin against various cancers. In order to avoid adverse effects, such as ulcers, associated with aspirin's oral admin-istration, it has been proposed its combination at lower conc-entrations with other chemopreventive compounds. This combination would potentate aspirin's ability to inhibit neoplastic cells proliferation and to induce apoptosis. Lunasin is a 43-amino acid peptide initially discovered in soybean, and then, identified in other seeds and plants. Lunasin has been found to exert anti-carcinogenic activity both in in vitro and in vivo assays, as well as anti-inflammatory and antioxidant properties. It has been demon-strated, in cell culture and xenograft mouse models, to play a chemo-preventive role against breast cancer. Moreover, lunasin has been found to potentate breast cancer cells proliferation inhibitory and apoptosis inducing properties of aspirin. These results demonstrate that lunasin not only acts as a promising anti-cancer agent, but also as an auxiliary agent in chemopreventive therapy. This review summarizes the bioactivity and molecular mechanism of action of aspirin, alone or in combination with lunasin and other chemopreventive agents against cancer. Different vitamins, minerals, phytochemicals, and chemical drugs have been used in combination with aspirin to achieve a better chemopreventive effect.