NDLI: The induction of lysis in lysogenic strains of Escherichia coli by a new antitumor transplatin derivative and its DNA interactions

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Gibson, Dan Pracharova, Jitka Kasparkova, Jana Brabec, Viktor Novakova, Olga
Description	Author Affiliation: Brabec V ( Institute of Biophysics, Academy of Sciences of the Czech Republic, v.v.i.., Kralovopolska 135, CZ-61265 Brno, Czech Republic. brabec@ibp.cz.)
Abstract	The toxicity of the new derivative of transplatin, namely $trans-[PtCl_{2}(DEA)(NH_{3})]$ (DEA = diethylamine), in which only one $NH_{3}$ group was replaced by a small, non-bulky DEA ligand, in the cisplatin sensitive and resistant tumor cell lines was examined. The results indicate that this very small modification of the transplatin molecule results in a considerable enhancement of toxicity in the cancer cells. Thus, this finding is consistent with the thesis that the trans geometry in $Pt^{II}-dichlorido$ compounds can also be effectively activated by the replacement of only one $NH_{3}$ ligand in transplatin by the non-bulky ligand, such as the short aliphatic amine, $(C_{2}H_{5})_{2}NH.$ We also demonstrate that $trans-[PtCl_{2}(DEA)(NH_{3})],$ in contrast to transplatin, can be grouped with the coordination compounds exhibiting antitumor activity and capable of inducing lysis in lysogenic bacteria. Thus, these results afford, for the first time, experimental support for the view that DNA is the potential cellular target also for antitumor derivatives of transplatin. DNA binding mode of $trans-[PtCl_{2}(DEA)(NH_{3})]$ in cell-free media was examined as well. The results show that the small aliphatic DEA ligand has significant consequences for the DNA conformational changes. Unlike ‘classical’ transplatin, modification of DNA with $trans-[PtCl_{2}(DEA)(NH_{3})]$ leads to mainly bifunctional cross-links. The extent and destabilization of the double-helical structure of DNA by this new trans-platinum complex are similar to those induced by cisplatin. As a consequence the lesions effectively inhibit transcription of template DNA similarly to the lesions of cisplatin, but markedly more than the lesions of transplatin. The stronger inhibition of DNA transcription by the adducts of $trans-[PtCl_{2}(DEA)(NH_{3})]$ in comparison with the adducts of transplatin adds a new dimension to the impact of the activated trans geometry in platinum compounds on biological processes, possibly including DNA transcription.
ISSN	14779226
Issue Number	8
Volume Number	44
e-ISSN	13645447
Journal	Dalton Trans.
Language	English
Publisher	Royal Society of Chemistry
Publisher Date	2015-02-28
Publisher Place	Great Britain (UK)
Access Restriction	Subscribed
Subject Keyword	Antineoplastic Agents Chemistry Cisplatin DNA Pharmacology Apoptosis Drug Effects Cell Line, Tumor Circular Dichroism Metabolism DNA Adducts Escherichia Coli Genetics Humans MCF-7 Cells Transcription, Genetic Journal Article Research Support, Non-U.S. Gov't
Content Type	Text
Resource Type	Article
Subject	Inorganic Chemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in