Toxicity assessments and transcriptional effects of monofunctionalized Pt(II) complex under dark and light irradiation condition in Caenorhabditis elegans

Hui Chong; Siyu Fang; Di Yang; Chuan Tan; Junjie Wei; Shu-Han Chang; Hongying Fan; Hang Yao; Aijian Qin; Hongxia Shao; Yuefei Zhang; Junling Leng; Dawei Su; Chengyin Wang; Hualing Li

doi:10.1016/j.jinorgbio.2022.111720

Toxicity assessments and transcriptional effects of monofunctionalized Pt(II) complex under dark and light irradiation condition in Caenorhabditis elegans

J Inorg Biochem. 2022 May:230:111720. doi: 10.1016/j.jinorgbio.2022.111720. Epub 2022 Jan 6.

Authors

Hui Chong¹, Siyu Fang², Di Yang³, Chuan Tan², Junjie Wei³, Shu-Han Chang⁴, Hongying Fan⁵, Hang Yao², Aijian Qin⁶, Hongxia Shao⁶, Yuefei Zhang⁷, Junling Leng⁷, Dawei Su⁸, Chengyin Wang⁹, Hualing Li¹⁰

Affiliations

¹ College of Chemistry and Chemical Engineering, Yangzhou University, 180 Si-Wang-Ting Road, 225002, Yangzhou, Jiangsu Province, China. Electronic address: [email protected].
² College of Chemistry and Chemical Engineering, Yangzhou University, 180 Si-Wang-Ting Road, 225002, Yangzhou, Jiangsu Province, China.
³ Institute of Translational Medicine, Medical College, Yangzhou University, City of Yangzhou, Jiangsu Province 225001, China.
⁴ Department of Acupuncture and Moxibustion, Yangzhou Hospital of Traditional Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, City of Yangzhou, Jiangsu Province 225012, China.
⁵ Testing Centre of Yangzhou University, City of Yangzhou, Jiangsu Province 225009, China.
⁶ Ministry of Education Key Lab for Avian Preventive Medicine, Key Laboratory of Jiangsu Preventive Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, City of Yangzhou, Jiangsu Province 225009, China.
⁷ Department of Emergency, Affiliated Hospital of Yangzhou University, Yangzhou 225000, Jiangsu, China.
⁸ Center for Clean Energy Technology, School of Mathematical and Physical Science, Faculty of Science, University of Technology Sydney, NSW 2000, Australia. Electronic address: [email protected].
⁹ College of Chemistry and Chemical Engineering, Yangzhou University, 180 Si-Wang-Ting Road, 225002, Yangzhou, Jiangsu Province, China. Electronic address: [email protected].
¹⁰ Institute of Translational Medicine, Medical College, Yangzhou University, City of Yangzhou, Jiangsu Province 225001, China; Jiangsu Key laboratory of integrated traditional Chinese and Western Medicine for prevention and treatment of Senile Diseases, Yangzhou University, City of Yangzhou, Jiangsu Province 225001, China; Jiangsu Key Laboratory of Zoonosis, Yangzhou University, City of Yangzhou, Jiangsu Province 225001, China. Electronic address: [email protected].

PMID: 35221123
DOI: 10.1016/j.jinorgbio.2022.111720

Abstract

In vivo toxicity of aromatic ring (BODIPY, 1,3,5,7,8-pentamethyl dipyrrin borondifluoride) attached monofunctional Pt(II) complexes mCBP {[cis-Pt(NH₃)₂Cl] 8-(para-pyridine-methylene),1,3,5,7-tetramethyl dipyrrin borondifluoride}⁺ Nitrate^- and dCBP {[cis-Pt(NH₃)₂Cl]₂8-(1,3-pyrimidine-5-methylene),1,3,5,7-tetramethyl dipyrrin borondifluoride}²⁺ diNitrate^2- were tested in Caenorhabditis elegans (C. elegans). dCBP showed promising reactive oxygen ROS (reactive oxygen species) generating capability. This complex resulted reduction of lifespan, body length and egg laying rate under dark and light irradiation in both N2 (wild-type, cisplatin resistant) and ok938 (asna-1, cisplatin sensitive) C. elegans. Expressional change of several key cancer related pathway (JNK (c-Jun N-terminal kinase) and Wnt/β-catenin (Wingless/Integrated/β-catenin)) related genes (for instance, jnk-1, wrm-1 and gst-4) were confirmed by RNA sequencing experiments. These transcriptional alternations could explain physiological parameters change in nematode and partially revealed how both Pt(II) based complexes influence cancer related pathways. Furthermore, these associated genes exhibited the function of apoptosis, reduced chemoresistance of cancer cells and most of those expressional changes were linked to extended survival of cancer patients.

Keywords: Caenorhabditis elegans; Monofunctionalized Pt(II) complex; ROS; Toxicity; Transcriptional influence.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Caenorhabditis elegans Proteins* / genetics
Caenorhabditis elegans Proteins* / metabolism
Caenorhabditis elegans*
Cisplatin / pharmacology
Cytoskeletal Proteins / genetics
Cytoskeletal Proteins / metabolism
Cytoskeletal Proteins / pharmacology
Humans
Platinum / pharmacology*
Reactive Oxygen Species / metabolism
beta Catenin / metabolism
beta Catenin / pharmacology

Substances

Caenorhabditis elegans Proteins
Cytoskeletal Proteins
Reactive Oxygen Species
WRM-1 protein, C elegans
beta Catenin
Platinum
Cisplatin