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Combination therapy consists in the simultaneous administration of a conventional chemotherapy drug (or sometimes, a radiotherapy protocol) together with one or more natural bioactives (usually from plant or fungal origin) of small molecular weight. This combination of anticancer drugs may be applied to cell cultures of tumor cells, or to an animal model for a cancer type (or its xenograft), or to a clinical trial in patients. In this review, we summarize current knowledge describing diverse synergistic effects on colorectal cancer cell cultures, animal models, and clinical trials of various natural bioactives (stilbenes, flavonoids, terpenes, curcumin, and other structural families), which may be important with respect to diminish final doses of the chemotherapy drug, although maintaining its biological effect. This is important as these approaches may help reduce side effects in patients under conventional chemotherapy. Also, these molecules may exerts their synergistic effects via different cell cycle pathways, including different ones to those responsible of resistance phenotypes: transcription factors, membrane receptors, adhesion and structural molecules, cell cycle regulatory components, and apoptosis pathways.

Synthetic antioxidant food additives, such as BHA, BHT and TBHQ, are going through a difficult time, since these products generate a negative perception in consumers. This has generated an increased pressure on food manufacturers to search for safer natural alternatives like phytochemicals (such as polyphenols, including flavonoids, and essential oils rich in terpenoids, including carotenoids). These plant bioactive compounds have antioxidant activities widely proven in in vitro tests and in diverse food matrices (meat, fish, oil and vegetables). As tons of food are wasted every year due to aesthetic reasons (lipid oxidation) and premature damage caused by inappropriate packaging, there is an urgent need for natural antioxidants capable of replacing the synthetic ones to meet consumer demands. This review summarizes industrially interesting antioxidant bioactivities associated with terpenoids and polyphenols with respect to the prevention of lipid oxidation in high fat containing foods, such as meat (rich in saturated fat), fish (rich in polyunsaturated fat), oil and vegetable products, while avoiding the generation of rancid flavors and negative visual deterioration (such as color changes due to oxidized lipids). Terpenoids (like monoterpenes and carotenoids) and polyphenols (like quercetin and other flavonoids) are important phytochemicals with a broad range of antioxidant effects. These phytochemicals are widely distributed in fruits and vegetables, including agricultural waste, and are remarkably useful in food preservation, as they show bioactivity as plant antioxidants, able to scavenge reactive oxygen and nitrogen species, such as superoxide, hydroxyl or peroxyl radicals in meat and other products, contributing to the prevention of lipid oxidation processes in food matrices.