Gallic acid, a major component of Toona sinensis leaf extracts, contains a ROS-mediated anti-cancer activity in human prostate cancer cells.
Prostate cancer, the most frequently diagnosed malignancy in elderly males of the United States, has become a major health issue in Asia. Previous studies have demonstrated that leaf extracts of Toona sinensis Roem. contain cytotoxic activity on several cancer cells including prostate cancer cells. In this study, gallic acid is identified as the major anti-cancer compound in T. sinensis leaf extracts. It is cytotoxic to DU145 prostate cancer cells, through generation of reactive oxygen species (ROS) and mitochondria-mediated apoptosis, which were reversed by antioxidants catalase and N-acetylcysteine. Furthermore, gallic acid is shown to block the growth of DU145 cells at G2/M phases by activating Chk1 and Chk2 and inhibiting Cdc25C and Cdc2 activities. In addition, gallic acid has a synergistic effect with doxorubicin in suppressing the growth of DU145 cells. Taken together, our results suggest that gallic acid has the potential to be developed into an anti-prostate cancer drug and is worthy of further studies.
Chen
Huei-Mei
HM
Graduate Institute of Natural Products, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan, ROC.
Wu
Yang-Chang
YC
Chia
Yi-Chen
YC
Chang
Fang-Rong
FR
Hsu
Hseng-Kuang
HK
Hsieh
Ya-Ching
YC
Chen
Chih-Chen
CC
Yuan
Shyng-Shiou
SS
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000071877:Checkpoint Kinase 1; D064447:Checkpoint Kinase 2; D020552:Comet Assay; D019926:Cyclin B / Q000378:metabolism; D018844:Cyclin-Dependent Kinases; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D004357:Drug Synergism; D005434:Flow Cytometry; D005707:Gallic Acid / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015151:Immunoblotting; D008297:Male; D029582:Meliaceae / Q000737:chemistry*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015394:Molecular Structure; D018515:Plant Leaves / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020687:cdc25 Phosphatases / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D019926:Cyclin B; D017382:Reactive Oxygen Species; D005707:Gallic Acid; D004317:Doxorubicin; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C000605867:CHEK1 protein, human; C578634:CHEK2 protein, human; D000071877:Checkpoint Kinase 1; D017346:Protein Serine-Threonine Kinases; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases