Institute of Nautical Medicine, Nantong University, Nantong 226001, China.
Invest New Drugs. 2012 Feb;30(1):17-24. doi: 10.1007/s10637-010-9508-1. Epub 2010 Aug 10.
A novel series of 4β-[(4-substituted) aroylthiourea] derivatives of podophyllotoxin were synthesized and their abilities to inhibit the growth of cancer cells were investigated by MTT assay. Compound 4a possessed the highest cytotoxicity on HepG2, A549 and HCT-116 cancer cell lines with the IC(50) values of 0.1 μM. Apoptosis in HCT-116 cells induced by compound 4a was observed by Hoechst33342-Propidium iodide (PI) and acridine orange (AO)-ethidium bromide (EB) double staining assays. DNA flow cytometric analysis revealed that 4a induced cell cycle arrest at G2/M phase and kDNA decatenation assay indicated that 4a inhibited topoisomerase IIα-mediated kDNA decatenation. Our results indicated that compound 4a possessed promising antitumor activity, which need to be studied further.
我们合成了一系列新型的 4β-[(4-取代)芳酰基硫脲]鬼臼毒素衍生物，并通过 MTT 法研究了它们抑制癌细胞生长的能力。化合物 4a 对 HepG2、A549 和 HCT-116 癌细胞系表现出最高的细胞毒性，IC50值分别为 0.1 μM。通过 Hoechst33342-碘化丙啶（PI）和吖啶橙（AO）-溴化乙锭（EB）双重染色实验观察到化合物 4a 诱导 HCT-116 细胞凋亡。DNA 流式细胞术分析显示，4a 诱导细胞周期停滞在 G2/M 期，kDNA 解连环实验表明 4a 抑制拓扑异构酶 IIα介导的 kDNA 解连环。我们的结果表明，化合物 4a 具有有前途的抗肿瘤活性，需要进一步研究。
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