Bromocoumarinplatin, targeting simultaneously mitochondria and nuclei with p53 apoptosis pathway to overcome cisplatin resistance

Ma，Jing1; Li，Linrong1; Yue，Kexin1; Li，Yingguang1; Liu，Hanfang1; Wang，Peng George4; Wang，Chaojie3; Wang，Jiajia2; Luo，Wen3; Xie，Songqiang1

2020-06-01

10.1016/j.bioorg.2020.103768

BIOORGANIC CHEMISTRY   影响因子和分区

0045-2068

1090-2120

Mitochondria as one of potential anticancer target, alternatively damaging mtDNA other than nDNA is a potential method for platinum-based anticancer drugs to overcome cisplatin resistance. We herein report that bromocoumarinplatin 1, a coumarin-Pt(IV) prodrug, targeted simultaneously mitochondria and nuclei with the contents of Pt in nDNA and mtDNA were 25.75% and 65.91%, respectively, which demonstrated mtDNA apoptosis played a key role in overcoming cisplatin resistance. Moreover, 1 promoted the expression of p53 gene and protein more effectively than cisplatin, leading to the increased anticancer activity of 1 through p53 pathway. The property of preferential accumulation in cancer cells (Snu-368 and Snu-739) compared to the matched normal cells (HL-7702 cells) demonstrated that 1 was potentially safe for clinical therapeutic use. In addition, the higher therapeutic indices of 1 for HCT-116 cells in vivo indicated that bromocoumarinplatin behaved a vital function in the treatment of colon cancer.

SCI

英语

其他

National Natural Science Foundation of China[21807025][21907022][81573465] ; China Postdoctoral Science Foundation[2018M640673][2019M652528] ; Postdoctoral Research Grant in Henan Province[001802020] ; Key Scientific Research Projects in Henan Colleges and Universities[19A350002] ; Scientific Research Cultivating Program for Young Talents in Henan Medical School[2019006] ; Program for Innovative Research Team (in Science and Technology in University of Henan Province)[19IRTSTHN004] ; Project of Innovation and Entrepreneurship Support Program for College Students of Henan University Minsheng College[MSCXCY2018058] ; Henan University[201910475012][2019102004] ; key scientific research projects of universities in Henan province[202102310471]

Biochemistry & Molecular Biology ; Chemistry

Biochemistry & Molecular Biology ; Chemistry, Organic

WOS:000537405500002

ACADEMIC PRESS INC ELSEVIER SCIENCE

BIOLOGY & BIOCHEMISTRY

2-s2.0-85082009389

Scopus

1.School of Pharmacy,Institute for Innovative Drug Design and Evaluation,Henan University,475004, Kaifeng,Jinming Ave,China
2.Joint National Laboratory for Antibody Drug Engineering; School of Basic Medicine Science,Henan University,Kaifeng,China
3.The Key Laboratory of Natural Medicine and Immuno-Engineering,Henan University,Kaifeng,China
4.School of Medicine,Southern University of Science and Technology,Shenzhen,518005,China

Ma，Jing,Li，Linrong,Yue，Kexin,et al. Bromocoumarinplatin, targeting simultaneously mitochondria and nuclei with p53 apoptosis pathway to overcome cisplatin resistance[J]. BIOORGANIC CHEMISTRY,2020,99.

Ma，Jing.,Li，Linrong.,Yue，Kexin.,Li，Yingguang.,Liu，Hanfang.,...&Xie，Songqiang.(2020).Bromocoumarinplatin, targeting simultaneously mitochondria and nuclei with p53 apoptosis pathway to overcome cisplatin resistance.BIOORGANIC CHEMISTRY,99.

Ma，Jing,et al."Bromocoumarinplatin, targeting simultaneously mitochondria and nuclei with p53 apoptosis pathway to overcome cisplatin resistance".BIOORGANIC CHEMISTRY 99(2020).