Please use this identifier to cite or link to this item:
http://hdl.handle.net/1942/37527
Title: | Enhanced anticancer potency with reduced nephrotoxicity of newly synthesized platin-based complexes compared with cisplatin | Authors: | Salehi, Roya Abyar, Selda Ramazani, Fatemeh Khandar, Ali Akbar Hosseini-Yazdi, Seyed Abolfazl White, Jonathan M. Edalati, Mahdi KAHROBA, Houman Talebi, Mehdi |
Issue Date: | 2022 | Publisher: | NATURE PORTFOLIO | Source: | Scientific Reports, 12 (1) (Art N° 8316) | Abstract: | As a platinum-containing anticancer drug, cisplatin is the keystone for treating many malignancies. Nephrotoxicity is the main dose-limiting toxicity, and several hydration therapies and supplementary strategies are utilized to reduce cisplatin-induced kidney damage, so the discovery and development of effective and safe antitumor drugs are still on the path of human health. Herein, a new four-coordinated Pt complex [Pt(TSC)Cl] using N(4)-phenyl-2-formylpyridine thiosemicarbazone (HTSC) was synthesized and characterized by single-crystal X-ray diffraction, (HNMR)-H-1, FT-IR, LC/MS and CHN elemental analysis. The Pt(TSC)Cl complex revealed antiproliferative activity against A549, MCF-7 and Caco-2 cell lines with a low micromolar IC50 (200-1.75 mu M). Specifically, the Pt(TSC)Cl complex displayed more selectivity in Caco-2 cells (IC50 = 2.3 mu M) than cisplatin (IC50 = 107 mu M) after 48 h of treatment. Moreover, compared with cisplatin, a known nephrotoxic drug, the Pt(TSC)Cl complex exhibited lower nephrotoxicity against Hek293 normal cells. We also found that the Pt(TSC)Cl complex can effectively prevent cancer cell propagation in sub-G1 and S phases and induce apoptosis (more than 90%). Real time PCR and western analysis demonstrated that the expression pattern of apoptotic genes and proteins is according to the intrinsic apoptosis pathway through the Bax/Bcl-2-Casp9-Casp3/Casp7 axis. Collectively, our findings indicated that the Pt(TSC)Cl complex triggers apoptosis in Caco-2 cell lines, while low nephrotoxicity was shown and may be considered a useful anticancer drug candidate for colorectal cancers for further optimization and growth. | Notes: | Salehi, R (corresponding author), Tabriz Univ Med Sci, Fac Adv Med Sci, Drug Appl Res Ctr, Tabriz 5165665811, Iran.; Salehi, R (corresponding author), Tabriz Univ Med Sci, Fac Adv Med Sci, Dept Med Nanotechnol, Tabriz 5165665811, Iran.; Khandar, AA (corresponding author), Univ Tabriz, Fac Chem, Dept Inorgan Chem, Tabriz 5166614766, Iran. salehiro@tbzmed.ac.ir; akhandar@yahoo.com |
Keywords: | Apoptosis;Caco-2 Cells;Cell Line, Tumor;HEK293 Cells;Humans;Spectroscopy, Fourier Transform Infrared;Antineoplastic Agents;Cisplatin | Document URI: | http://hdl.handle.net/1942/37527 | ISSN: | 2045-2322 | e-ISSN: | 2045-2322 | DOI: | 10.1038/s41598-022-11904-3 | ISI #: | WOS:000797636300031 | Rights: | Te Author(s) 2022 Open Access Tis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. Te images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2023 |
Appears in Collections: | Research publications |
Files in This Item:
File | Description | Size | Format | |
---|---|---|---|---|
Enhanced anticancer potency with reduced nephrotoxicity of newly synthesized platin-based complexes compared with cisplatin.pdf | Published version | 2.48 MB | Adobe PDF | View/Open |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.