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Plant flavone apigenin binds to nucleic acid bases and reduces oxidative DNA damage in prostate epithelial cells.

Abstract
Oxidative stress has been linked to prostate carcinogenesis as human prostate tissue is vulnerable to oxidative DNA damage. Apigenin, a dietary plant flavone, possesses anti-proliferative and anticancer effects; however, its antioxidant properties have not been fully elucidated. We investigated sub-cellular distribution of apigenin, it's binding to DNA and protective effects against H2O2-induced DNA damage using transformed human prostate epithelial RWPE-1 cells and prostate cancer LNCaP, PC-3 and DU145 cells. Exposure of cells to apigenin exhibited higher accumulation in RWPE-1 and LNCaP cells, compared to PC-3 and DU145 cells. The kinetics of apigenin uptake in LNCaP cells was estimated with a Km value of 5 µmole/L and Vmax of 190 pmoles/million cells/h. Sub-cellular fractionation demonstrated that nuclear matrix retains the highest concentration of apigenin (45.3%), followed by cytosol (23.9%), nuclear membranes (17.9%) and microsomes (12.9%), respectively. Spectroscopic analysis of apigenin with calf-thymus DNA exhibited intercalation as the dominant binding mode to DNA duplex. Apigenin exposure resulted in significant genoprotective effects in H2O2-stressed RWPE-1 cells by reduction in reactive oxygen species levels. In addition, apigenin exposure suppressed the formation of 8-hydroxy-2' deoxyguanosine and protected exposed cells from apoptosis. Our studies demonstrate that apigenin is readily taken up by normal prostatic epithelial cells and prostate cancer cells, and is incorporated into their nuclei, where its intercalation with nucleic acid bases may account for its antioxidant and chemopreventive activities.
AuthorsHaripaul Sharma, Rajnee Kanwal, Natarajan Bhaskaran, Sanjay Gupta
JournalPloS one (PLoS One) Vol. 9 Issue 3 Pg. e91588 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID24614817 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References
  • Nucleic Acids
  • Reactive Oxygen Species
  • Apigenin
  • 8-Hydroxy-2'-Deoxyguanosine
  • DNA
  • calf thymus DNA
  • Hydrogen Peroxide
  • Deoxyguanosine
Topics
  • 8-Hydroxy-2'-Deoxyguanosine
  • Apigenin (chemistry, pharmacology)
  • Cell Death (drug effects)
  • Cell Line, Tumor
  • Cytoprotection (drug effects)
  • DNA (metabolism)
  • DNA Damage
  • Deoxyguanosine (analogs & derivatives, metabolism)
  • Endocytosis (drug effects)
  • Epithelial Cells (drug effects, metabolism)
  • Humans
  • Hydrogen Peroxide (toxicity)
  • Kinetics
  • Male
  • Nucleic Acids (metabolism)
  • Oxidation-Reduction (drug effects)
  • Prostate (cytology)
  • Prostatic Neoplasms (pathology)
  • Reactive Oxygen Species (metabolism)
  • Spectrophotometry, Ultraviolet
  • Subcellular Fractions (drug effects, metabolism)

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