Chemopreventive role of aspirin and its combinations 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. 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) inhibits cycloxygenase (COX) enzyme, reducing inflammation associated to several types of cancer, such as colorectal, breast, lung, prostate, oesophagus, stomach and ovary cancers. Epidemiological evidence suggests a promising chemopreventive role of aspirin against various cancers. In order to avoid adverse effects, such as ulcers, associated with aspirin's oral administration, it has been proposed its combination at lower concentrations with other chemopreventive compounds. Lunasin is a 43-amino acid peptide initially discovered in soybean, and then, identified in other seeds. 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 demonstrated lunasin plays a chemopreventive role against breast cancer in the MDAMB-231 cell culture, and in a xenograft breast cancer cell and chemical carcinogeninduced mouse models. Moreover, lunasin has also 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.