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Cell cycle–dependent uptake and cytotoxicity of arsenic-based drugs in single leukemia cells

Cell cycle–dependent uptake and cytotoxicity of arsenic-bas...

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第十一届全国化学生物学学术会议

作者： Ying Zhou Haibo Wang Eric Tse Hongyan Li Hongzhe Sun Department of Chemistry The University of Hong Kong Department of Medcine Queen Mary HospitalThe University of Hong Kong

Cell is a complex system whose components change with time and space,and heterogeneity is a widespread event existing in all cells .Most previous studies are based on bulk analysis which lead to the losing of key information about the distribution within one *** cell analysis gives us a more accurate result,offering comprehensive information on the fundamental mechanism of biological *** have long been used as therapeutic *** the mechanism of action of arsenic-based drugs enables more effective arsenic drugs to be *** cycle has been known to play a critical role for cell division and ***,we establish a methodology to evaluate the uptake of two arsenic-based drugs(ATO and ZIO-101) across the cell cycle in single leukemia cells,i.e.,NB4 and HL60,using a double thymidine block combined with time-resolved ICP-MS .We show that cells absorb maximal amounts of both ATO and ZIO-101 in G2/M phase and minimum in S phase,and such variation is less apparent for ZIO-101 than ATO(NB4-G2/M:S=2.5:1 for ATO and 1.6:1 for ZIO-101).We subsequently demonstrate that AQP9,an ATO transporter,is highly expressed in G1 phase(50.2%-46.9%) and least expressed in S phase(27.6%-24.6%);while xCT,a ZIO-101 transporter,is mostly expressed in G2/M phase(74.8%-76.1%),and least expressed in G1 phases(55.4-59.8%).Furthermore,we show that the cytotoxicity of ATO and ZIO-101 on NB4 cells is also cell cycle dependent,with the highest cytotoxicity at S+G2/M phase and the lowest at G1+S *** studies provide the first evidence on cell cycle dependent uptake and cytotoxicity of arsenic-based drugs at single cell levels,may have general implications for precise evaluation of other anticancer drugs by considering cell cycle phase.

关键词： Single cell Cell cycle arsenic-based drugs leukemia

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