Toona sinensis extracts induces apoptosis via reactive oxygen species in human premyelocytic leukemia cells.
Toona sinensis (T. sinensis), well known in Taiwan as a traditional Chinese medicine, has been shown to exhibit antioxidant effects. In this study, therefore, the ability of T. sinensis to induce apoptosis was studied in cultured human premyelocytic leukemia HL-60 cells. Treatment of the HL-60 cells with a variety of concentrations of the aqueous extracts of T. sinensis (TS extracts) (10-75 microg/ml) and gallic acid (5-10 microg/ml), the natural phenolic components purified from TS extracts, resulted in dose- and time-dependent sequences of events marked by apoptosis, as shown by loss of cell viability and internucleosomal DNA fragmentation. Furthermore, apoptosis in the HL-60 cells was accompanied by the release of cytochrome c, caspase 3 activation and specific proteolytic cleavage of poly (ADP-ribose) polymerase (PARP). This increase in TS extracts- and gallic acid-induced apoptosis was also associated with a reduction in the levels of Bcl-2, a potent cell-death inhibitor, and an increase in those of the Bax protein, which heterodimerizes with and thereby inhibits Bcl-2. Interestingly, TS extracts- and gallic acid-induced dose-dependent reactive oxygen species (ROS) generation in HL-60 cells. We found that catalase significantly decreased TS extracts- or gallic acid-induced cytotoxicity, DNA fragmentation, and ROS production, however, slight reduction was observed with vitamins C and E. Our results indicate that TS extracts- or gallic acid-induced HL-60 apoptotic cell death could be due to the generation of ROS, especially H(2)O(2). The data suggest that T. sinensis exerts antiproliferative action and growth inhibition on HL-60 cells through apoptosis induction, and, therefore, that it may have anticancer properties valuable for application in food and drug products.
Yang
Hsin-Ling
HL
Institute of Nutrition, China Medical University, Taichung, Taiwan.
Chang
Wen-Huei
WH
Chia
Yi-Chen
YC
Huang
Chin-Jung
CJ
Lu
Fung-Jou
FJ
Hsu
Hseng-Kuang
HK
Hseu
You-Cheng
YC
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000096:biosynthesis; D002374:Catalase / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005707:Gallic Acid / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D029582:Meliaceae / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; C494826:BAX protein, human; D004365:Drugs, Chinese Herbal; D010936:Plant Extracts; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D005707:Gallic Acid; D045304:Cytochromes c; D002374:Catalase; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3