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Author Zhou, Yao ♦ Zhao, Hong-Ye ♦ Jiang, Du ♦ Wang, Lu-Yao ♦ Xiang, Cen ♦ Wen, Shao-Peng ♦ Fan, Zhen-Chuan ♦ Zhang, Yong-Min ♦ Guo, Na ♦ Teng, Yu-Ou ♦ Yu, Peng
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ APOPTOSIS ♦ BORON CHLORIDES ♦ CELL PROLIFERATION ♦ CHLOROFORM ♦ CONCENTRATION RATIO ♦ DNA ♦ IN VITRO ♦ LARGE INTESTINE ♦ LEUKEMIA ♦ LIVER ♦ MAMMARY GLANDS ♦ MITOCHONDRIA ♦ TOXICITY ♦ TUMOR CELLS
Abstract The cytotoxic activity of camptothecin derivatives is so high that these compounds need to be further modified before their successful application as anti-cancer agents clinically. In this study, we reported the synthesis and biological evaluation of a novel camptothecin derivative called compound 2–47. The changes in structure did not reduce its activity to inhibit DNA topoisomerase I. Compound 2–47 induced apoptosis of many tumor cells including leukemia cells K562, Jurkat, HL-60, breast cancer cell BT-549, colon cancer cell HT-29 and liver cancer cell HepG2 with a half maximal inhibitory concentration (IC{sub 50}) of 2- to 3-fold lower than HCPT as a control. In particular, 2–47 inhibited the proliferation of Jurkat cells with an IC{sub 50} of as low as 40 nM. By making use of Jurkat cell as a model, following treatment of Jurkat cells, compound 2–47 activated caspase-3 and PARP, resulting in a decreased Bcl-2/Bax ratio. These data showed that compound 2–47 induces Jurkat cell death through the mitochondrial apoptotic pathway. In addition, compound 2–47 showed a decreased cytotoxic activity against normal cells and an improved solubility in low-polar solvent. For example, compound 2–47 solutes in CHCl{sub 3} 130-fold higher than HCPT. Taken together, our data demonstrated that camptothecin derivative 2–47 notably inhibits the tumor cell proliferation through mitochondrial-mediated apoptosis in vitro. - Highlights: • Compound 2–47 showed a wide inhibitory effect on the tested tumor cell lines with an IC{sub 50} of 3 times lower than that of HCPT in general. • Compound 2–47 inhibited the proliferation of the human leukemia cell Jurkat at an IC{sub 50} of as low as 40 nM. • As compared to HCPT, compound 2–47 showed much reduced cytotoxicity on normal human cells. • As compared to others, compound 2–47 showed a hundreds-fold higher solubility in non-polar organic solution.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2016-04-08
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 472
Issue Number 3


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