Abstract
The use of plant polyphenols to prevent cancer has been studied extensively. However, recent findings regarding the cancer-promoting effects of some antioxidants have led to reservations regarding the therapeutic use of food-derived antioxidants including polyphenols. The aim of this study was to evaluate the therapeutic potential of food-derived polyphenols and their use and safety in cancer patients. The free-radical scavenging ability of sulforaphane and various food-derived polyphenols including curcumin, epigallocatechin gallate, epicatechin, pelargonidin, and resveratrol was compared with their growth inhibitory effect on ovarian cancer cells. Oxidative stress and/or antioxidant responses and anti-proliferative pathways were evaluated after administering sulforaphane and polyphenols at doses at which they have been shown to inhibit the growth of ovarian cancer cells. No correlation was observed between their ability to scavenge free radicals and their ability to inhibit the growth of ovarian cancer cells. With the exception of epigallocatechin gallate, all of the antioxidants that were tested at doses that inhibited cell growth significantly increased NAD(P)H quinone dehydrogenase I (NQO1) expression but induced cell cycle arrest and/or apoptotic signaling. Epigallocatechin gallate exhibited a higher free radical scavenging activity but did not induce NQO1 expression at either the mRNA or at the protein level. Treatment with polyphenols at physiological doses did not significantly alter the growth of ovarian cancer cells or NQO1 expression. Therefore, individual food-derived polyphenols appear to have different anti-cancer mechanisms. Their modes of action in relation to their chemical properties should be established, rather than collectively avoiding the use of these agents as antioxidants.
Highlights
A multitude of epidemiological studies have suggested that plant foods may help reduce the risk of cancer [1]
The ability of various polyphenols found in food to reduce DPPH and ABTSþ radicals (Fig. 1A) was measured and compared with Sul, which is known to be a strong inducer of NAD(P)H:quinone oxidoreductase-1 (NQO1) [19]
The rest of compounds are flavonoids; Epi and EGCG are classified as flavan-3-ols and Cya, malvidin chloride (Mal), and pelargonidin chloride (Pel) are anthocyanidins
Summary
A multitude of epidemiological studies have suggested that plant foods may help reduce the risk of cancer [1]. Plant foods rich in antioxidants are thought to prevent cancer because they protect cells from damage, especially DNA damage, which can increase the risk of developing cancer [2]. Oral supplementation with N-acetylcysteine (NAC) or vitamin E after the induction of lung cancer has been reported to increase tumor progression and to reduce survival in both B-RAF- and K-RAS-induced mouse models of lung cancer [3]. NAC administered after the formation of small nevi increased lymph-node metastases in a transgenic mouse model of melanoma [4]. In keeping with these preclinical results, a meta-analysis found that high consumption (20e30 mg/day) of b-carotene was significantly associated with a higher risk of lung cancer among current smokers [5]. A large phase III randomized placebo-controlled trial concluded that dietary supplementation with vitamin E (400 IU of a-tocopheryl acetate/day) significantly increased the risk of prostate cancer in men who were otherwise healthy [6]
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