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|Title: ||Differential modulation of benzo[a]pyrene-derived DNA adducts in MCF-7 cells by marine compounds.|
|Authors: ||M. Arif, Jamal.|
M. Siddiqui, Yunus.
A. El Sayed, Khalid.
Y. Orabi, Khaled.
N. Al-Ahdal, Mohammed.
M. Al-Khodairy, Fahad.
|Issue Date: ||2004 |
|Publisher: ||NOVA PUPLISHER|
|Abstract: ||Despite several marine anticancer compounds to be DNA-interactive, causing from reductive DNA cleavage to DNA adduct formation, not much attention has been given to the DNA adduct as early biomarker in the screening and development of marine anticancer drugs. Most of these compounds have been tested in vitro by high-throughput cost-effective screening assays for their anticancer potential. In the present study, chemically diverse marine compounds were screened using benzo[a]pyrene (BP)-derived DNA adduct formation in MCF-7 cells. Briefly, MCF-7 cells were incubated with the marine compounds, namely manzamine A, sarcophine, aaptamine, verongiaquinol, curcuphenol, and curcudiol (10, 50 and 100 μM) for 24 h followed by treatment with BP (0.5 μM). After 24 h re-incubation, cellular DNA was isolated and analyzed for BP-derived DNA adducts by 32P-postlabeling technique. Interestingly, at 50 μM dose, only manzamine A, a probable antitumor compound, increased the BP-DNA adducts by 3-folds while curcuphenol and curcudiol lowered the BP-DNA adduction by up to 50%. Other compounds insignificantly modulated the BP-DNA adduction. At 10 μM, all the marine compounds were ineffective except aaptamine, which induced BP-DNA adduction by 2-fold. Further at 100 μM dose, all the compounds except manzamine A and verongiaquinol increased the BP-DNA adducts by up to 500%. In addition, verongiaquinol (50 μM) substantially down-regulated the levels of p53, p21, and p16, while manzamine A (50 μM), significantly inhibited the expression of p53. Aaptamine (50 μM) induced the p53 expression by 40%, however, other compounds were ineffective. All other marine compounds resulted in a differential response related to p21 and p16 expression.|
|Appears in Collections:||College of Science|
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