Chenopodium album metabolites act as dual topoisomerase inhibitors and induce apoptosis in the MCF7 cell line

被引:10
作者
Chakraborty, Debanjana [1 ]
Jain, Chetan Kumar [2 ]
Maity, Arindam [1 ]
Ghosh, Shekhar [1 ]
Choudhury, Susanta Roy [3 ]
Jha, Tarun [4 ]
Majumder, Hemanta K. [2 ]
Mondal, Nirup B. [1 ]
机构
[1] Indian Inst Chem Biol, Council Sci & Ind Res, Dept Chem, 4 Raja SC Mullick Rd, Kolkata 700032, W Bengal, India
[2] Indian Inst Chem Biol, Council Sci & Ind Res, Mol Parasitol Lab, 4 Raja SC Mullick Rd, Kolkata 700032, W Bengal, India
[3] Saroj Gupta Canc Ctr & Res Inst, Div Res, MG Rd, Kolkata 700063, W Bengal, India
[4] Jadavpur Univ, Div Med & Pharmaceut Chem, Dept Pharmaceut Technol, POB 17020, Kolkata 700032, W Bengal, India
关键词
LEUKEMIA-CELLS; SEED EXTRACT; S-PHASE; CANCER; REPLICATION; ACTIVATION; TOXICITY; POISONS; ARREST; ATM;
D O I
10.1039/c5md00502g
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Desgalactotigonin (DGT) and oleanolic acid 3-O-beta-D-glucuronide (OAG) were isolated from Chenopodium album seeds, characterized using spectral analysis and evaluated for cytotoxic activity against various cancer cell lines. DGT and OAG induced apoptosis in a human breast cancer cell line (MCF-7) and were found to effectively inhibit human topoisomerases I and II in vitro. The study of the mode of enzyme inhibition revealed that both acted as catalytic inhibitors. IC50 values for DGT and OAG on MCF-7 cells were found to be 8.27 mu M and 11.33 mu M respectively. Using FACS and western blot analysis, the compounds were observed to block the cell cycle at S phase. Activation of caspases 7 and 9 suggested that caspase pathways were involved in inducing apoptosis.
引用
收藏
页码:837 / 844
页数:8
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