Disparate effects of similar phenolic phytochemicals as inhibitors of oxidative damage to cellular DNA

Abstract

Phenolic phytochemicals are natural plant substances whose cellular effects have not been completely determined. Nordihydroguaiaretic acid (NDGA) and curcumin are two phenolic phytochemicals with similar molecular structures, suggesting that they possess comparable chemical properties particularly in terms of antioxidant activity. To examine this possibility in a cellular system, this study evaluated the capacities of NDGA and curcumin to function as antioxidants in inhibiting oxidative damage to DNA. Jurkat T-lymphocytes were pre-incubated for 30 min with 0-25 microM of either NDGA or curcumin to allow for uptake. The phenolic phytochemical-treated cells were then oxidatively challenged with 25 microM hydrogen peroxide (H2O2). Afterwards, cells were subjected to alkaline micro-gel electrophoresis (i.e. comet assay) to assess the extent of single-strand breaks in DNA. In a concentration-dependent manner, NDGA inhibited H2O2-induced DNA damage, whereas curcumin did not. In fact, incubating Jurkat T-lymphocytes with curcumin alone actually induced DNA damage. This effect of curcumin on DNA did not appear to reflect the DNA fragmentation associated with apoptosis because there was no proteolytic cleavage of poly-(ADP-ribose)-polymerase, which is considered an early marker of apoptosis. Curcumin-induced damage to DNA was prevented by pre-treatment of the cells with the lipophilic antioxidant, alpha-tocopherol, suggesting that curcumin damaged DNA through oxygen radicals. Therefore, it is concluded that NDGA has antioxidant activity but curcumin has prooxidant activity in cultured cells based on their opposite effects on DNA.

Chemo-resistant melanoma sensitized by tamoxifen to low dose curcumin treatment through induction of apoptosis and autophagy

“…In a study by Kelly et al on Jurkat T-lymphocytes, curcumin's pro-oxidant activity was evident once it failed to not only prevent DNA damage (breaks in the DNA), but in fact was the cause of it. 25 In agreement with our findings, it has been speculated that below 50 μM, curcumin acts as a pro-oxidant in vitro in transformed cells, resulting in increased ROS production, mitochondrial swelling, dissipation of the mitochondrial membrane potential, disruption of redox homeostasis and release of cytochrome c.…”

Unpolished Thai Rice Prevents ACF Formation and Dysplastic Progression in AOM-Induced Rats and Induces Apoptosis Through Redox Alteration in CaCo-2 Cells

“…In this study, we found that UTR extract had significantly induced cellular oxidants in a dose dependent manner. This finding is in agreement with previous studies, various phytophenolics such as EGCG, curcumin, quercetin, and gallic acid can be generated ROS with dose-and time-dependent manners in various cancer cells (Kelly et al, 2001;Long et al, 2002). …”

The dark side of curcumin

“…21 Accumulating data have demonstrated since then that curcumin can induce DNA damage and chromosomal alterations both in vitro and in vivo at concentrations similar to those reported to exert beneficial effect. [22][23][24][25][26][27][28][29][30] For instance, curcumin concentrations of 2.5 and 5 lg mL À1 were shown to induce DNA damage to both the mitochondrial and nuclear genomes in cells. 28 These reports raise concern about curcumin safety, as the induction of DNA alterations is a common event in carcinogenesis.…”