Antioxidants cancer therapy

Biesalski, FI. K., and Frank, J. (2002). Antioxidants in cancer therapy Is there a rationale to recommend antioxidants during cancer therapy In "Thiol Metabolism and Redox Regulation of Cellular Functions" (A. Pompella, G. Banhegyi, and M. Wellman-Rousseau, eds.), NATO Science Series, Series I Life and Behavioural Sciences. Vol. 347, pp. 252-264. lOS Press, The Netherlands. 

Despite the numerous well-known complications of naturopathy and antioxidant therapy (antioxidants could blunt the effect of standard therapies, particularly alkylating, platinum, and tumor antibiotic agents, which are oxidative in nature), the biomedical research community has witnessed a remarkable optimism in the attitude of many conventional practitioners toward naturopathy and antioxidant therapy in recent years. Although this may appear as a theoretical concern, a plethora of pubhshed papers shows that this proposed interaction of anti- and pro-oxidant therapies has tremendous imphcations, and it is time to put this controversy in the proper perspective. Approaches to cancer therapy have been remarkably consistent for the last several decades. Smgeiy, radiation, and chemotherapy alone—or their reasonable... 

Fucoxanthin is known to be important free-radical scavengers and antioxidants for the prevention of oxidative damage, which is an important contributor in carcinogenesis. Therefore, it might be suggested that fucoxanthin has potent capacities for new anticancer product developments in the food industries as well as in pharmaceuticals as novel chemopreventing agents for cancer therapy. 

At present, numerous free radical studies related to many pathologies have been carried out. The amount of these studies is really enormous and many of them are too far from the scope of this book. The main topics of this chapter will be confined to the mechanism of free radical formation and oxidative processes under pathophysiological conditions. We will consider the possible role of free radicals in cardiovascular disorders, cancer, anemias, inflammation, diabetes mellitus, rheumatoid arthritis, and some other diseases. Furthermore, the possibilities of antioxidant and chelating therapies will be discussed. 

In 1965 1967 a great interest has been attached to the possible role of free radicals in cancer after studies by Emanuel and his coworkers who reported the excessive production of free radicals in tumor cells (see, for example, Ref. [145]). On these grounds the authors suggested to apply antioxidant therapy for the treatment of cancer patients. Unfortunately, experimental proofs of overproduction of free radicals in cancer tissue turn out to be erroneous [146], A new interest in the role of free radicals in cancer development emerged after the discovery of superoxide and superoxide dismutases. 

Pulmonary gene therapy is attractive for the treatmment of chronic bronchitis, cystic fibrosis, a-1 antitrypsin deficiency, familial emphysema, asthma, pulmonary infections, surfactant deficiency, pulmonary hypertension, lung cancer, and malignant mesothelioma. The pulmonary endothelium may act as a bioreactor for the production and secretion of therapeutic proteins, such as clotting factors and erythropoietin into the blood circulation. There is a potential benefit for acquired lung diseases, as well as cancers, to be controlled and possibly treated by expression of cytokines, surfactant, antioxidant enzymes, or mucoproteins within lung cells. 

The major pigment in Curcuma species (Zingiberaceae family) is the yellow phenolic diarylheptanoid curcumin (Jl). Curcumin and its analogs have potent antioxidant and antiinflammatory effects, cytotoxicity against tumor cells, and antitumor-promoting activity (96). The biologic effects and targets of curcumin, as well as its possible roles in cancer prevention and therapy, have been reviewed recently (97, 98). 

O Brien, P.J. Antioxidants and cancer molecular mechanisms. In Free Radicals in Diagnostic Medicine. A Systems Approach to Laboratory Technology, Clinical Correlations, and Antioxidant Therapy, Advances in Experimental Medicine and Biology, Armstrong, D., Ed. Plenum Press New York, 1994 366, 215-239. 

In the case of ifosfamide, the mechanism ofifosfamide-induced nephrotoxicity has been the topic of intense study which has yielded important clues as pathophysiology [54, 76-82], As noted above, ifosfamide is a prodrug that must undergo activation to ifosfamide mustard to exert its anticancer effects (Fig. 6). Ifosfamide metabolism can produce either ifosfamide mustard by ring hydrox-ylation or chloracetaldehyde by side chain oxidation [71, 77, 79], It has been demonstrated that chloracetaldehyde produced by intrarenal metabolism can act as a potent renal toxin, both in vitro and in vivo [76, 77, 80], It has also been clearly demonstrated that the use of concurrent antioxidant therapy—in the case of ifosfamide with 27-acetylcysteine—can prevent ifosfamide-induced renal injury, again both in vitro and in vivo [79-81], This approach has been shown in a small number of case reports to be effective in children with cancer [82],... 

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