Naphthalimide Platinum(IV) Compounds as Antitumor Agents with Dual DNA Damage Mechanism to Overcome Cisplatin Resistance

2018 ◽  
Vol 2018 (40) ◽  
pp. 4442-4451 ◽  
Author(s):  
Qingpeng Wang ◽  
Guoshuai Li ◽  
Zhifang Liu ◽  
Xiaoxiao Tan ◽  
Zhuang Ding ◽  
...  
Keyword(s):  
Dna Damage ◽  
Antitumor Agents ◽  
Cisplatin Resistance ◽  
Damage Mechanism

Design, synthesis and biological evaluation of dihydro-2-quinolone platinum(iv) hybrids as antitumor agents displaying mitochondria injury and DNA damage mechanism

2021 ◽  
Vol 50 (1) ◽  
pp. 362-375
Author(s):  
Zhifang Liu ◽  
Zuojie Li ◽  
Tao Du ◽  
Yan Chen ◽  
Qingpeng Wang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Antitumor Agents ◽  
Cisplatin Resistance ◽  
Damage Mechanism ◽  
Biological Evaluation ◽  
Antitumor Activities ◽  
Design Synthesis ◽  
Synthesis And Biological Evaluation

Dihydro-2-quinolone platinum(iv) hybrids exhibit effective antitumor activities by causing serious mitochondria injury and DNA damage, and show great potential in reversing cisplatin resistance and improving antitumor efficacies.

scholarly journals Platinum Complexes in Colorectal Cancer and Other Solid Tumors

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2073
Author(s):  
Beate Köberle ◽  
Sarah Schoch
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Dna Repair ◽  
Cancer Cells ◽  
Cisplatin Resistance ◽  
Platinum Complexes ◽  
Dna Lesions ◽  
Dna Damage Signaling ◽  
Repair Mechanisms ◽  
P53 Inactivation

Cisplatin is one of the most commonly used drugs for the treatment of various solid neoplasms, including testicular, lung, ovarian, head and neck, and bladder cancers. Unfortunately, the therapeutic efficacy of cisplatin against colorectal cancer is poor. Various mechanisms appear to contribute to cisplatin resistance in cancer cells, including reduced drug accumulation, enhanced drug detoxification, modulation of DNA repair mechanisms, and finally alterations in cisplatin DNA damage signaling preventing apoptosis in cancer cells. Regarding colorectal cancer, defects in mismatch repair and altered p53-mediated DNA damage signaling are the main factors controlling the resistance phenotype. In particular, p53 inactivation appears to be associated with chemoresistance and poor prognosis. To overcome resistance in cancers, several strategies can be envisaged. Improved cisplatin analogues, which retain activity in resistant cancer, might be applied. Targeting p53-mediated DNA damage signaling provides another therapeutic strategy to circumvent cisplatin resistance. This review provides an overview on the DNA repair pathways involved in the processing of cisplatin damage and will describe signal transduction from cisplatin DNA lesions, with special attention given to colorectal cancer cells. Furthermore, examples for improved platinum compounds and biochemical modulators of cisplatin DNA damage signaling will be presented in the context of colon cancer therapy.

scholarly journals Design, Synthesis and Pharmacological Evaluation of Three Novel Dehydroabietyl Piperazine Dithiocarbamate Ruthenium (II) Polypyridyl Complexes as Potential Antitumor Agents: DNA Damage, Cell Cycle Arrest and Apoptosis Induction

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1453
Author(s):  
Haoran Wang ◽  
Jianhua Wei ◽  
Hong Jiang ◽  
Ye Zhang ◽  
Caina Jiang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Antitumor Agents ◽  
Mechanistic Study ◽  
Ros Generation ◽  
Polypyridyl Complexes ◽  
Expression Levels ◽  
Cycle Arrest ◽  
Study Results

The use of cisplatin is severely limited by its toxic side-effects, which has spurred chemists to employ different strategies in the development of new metal-based anticancer agents. Here, three novel dehydroabietyl piperazine dithiocarbamate ruthenium (II) polypyridyl complexes (6a–6c) were synthesized as antitumor agents. Compounds 6a and 6c exhibited better in vitro antiproliferative activity against seven tumor cell lines than cisplatin, they displayed no evident resistance in the cisplatin-resistant cell line A549/DPP. Importantly, 6a effectively inhibited tumor growth in the T-24 xenograft mouse model in comparison with cisplatin. Gel electrophoresis assay indicated that DNA was the potential targets of 6a and 6c, and the upregulation of p-H2AX confirmed this result. Cell cycle arrest studies demonstrated that 6a and 6c arrested the cell cycle at G1 phase, accompanied by the upregulation of the expression levels of the antioncogene p27 and the down-regulation of the expression levels of cyclin E. In addition, 6a and 6c caused the apoptosis of tumor cells along with the upregulation of the expression of Bax, caspase-9, cytochrome c, intracellular Ca2+ release, reactive oxygen species (ROS) generation and the downregulation of Bcl-2. These mechanistic study results suggested that 6a and 6c exerted their antitumor activity by inducing DNA damage, and consequently causing G1 stage arrest and the induction of apoptosis.

The toxicity and DNA-damage mechanism of α-Fe2O3 nanoparticles

2016 ◽  
Vol 26 (2) ◽  
pp. 384-389
Author(s):  
Xiaoxing Wang ◽  
Yan Gu ◽  
Davidmark Johnson ◽  
Chuncheng Chen ◽  
Yingping Huang
Keyword(s):  
Dna Damage ◽  
Damage Mechanism ◽  
Fe2o3 Nanoparticles

scholarly journals The inhibition of MARK2 suppresses cisplatin resistance of osteosarcoma stem cells by regulating DNA damage and repair

2020 ◽  
Vol 23 ◽  
pp. 100290
Author(s):  
Liang Xu ◽  
Zhengkao Sun ◽  
Xianfu Wei ◽  
Hongdong Tan ◽  
Peng Kong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Dna Damage ◽  
Cisplatin Resistance ◽  
Dna Damage And Repair

Design and synthesis of a new series of low toxic naphthalimide platinum(IV) antitumor complexes with dual DNA damage mechanism

2018 ◽  
Vol 124 ◽  
pp. 127-136 ◽  
Author(s):  
Qingpeng Wang ◽  
Xiaoxiao Tan ◽  
Zhifang Liu ◽  
Guoshuai Li ◽  
Ruiyan Zhang ◽  
...  
Keyword(s):  
Dna Damage ◽  
Damage Mechanism ◽  
Design And Synthesis ◽  
Low Toxic ◽  
Antitumor Complexes
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