On the Discovery, Biological Effects, and Use of Cisplatin and Metallocenes in Anticancer Chemotherapy

Abstract

<jats:p>The purpose of this paper is to summarize mode of action of cisplatin on the tumor cells, a brief outlook on the metallocene compounds as antitumor drugs as well as the future tendencies for the use of the latter in anticancer chemotherapy. Molecular mechanisms of cisplatin interaction with DNA, DNA repair mechanisms, and cellular proteins are discussed. Molecular background of the sensitivity and resistance to cisplatin, as well as its influence on the efficacy of the antitumor immune response was evaluated. Furthermore, herein are summarized some metallocenes (titanocene, vanadocene, molybdocene, ferrocene, and zirconocene) with high antitumor activity.</jats:p>

Upregulated glutathione transferase omega-1 correlates with progression of urinary bladder carcinoma

“…Moreover, the high toxicity of cisplatin, due to its preferential binding to non-DNA targets, depends on the cellular redox state. Namely, it is known that only 5-10% intracellular concentration of cisplatin is found in DNA fraction, while 75-85% binds to nucleophilic sites of intracellular constituents, such as thiol-containing peptides, proteins, replication enzymes, and RNA [24]. It can be speculated that disturbances in redox status of tumor cells and increased GSTO1 deglutathionylase activity could affect this process through the changes in glutathionylation/deglutathionylation balance, in which case high thiol groups favor cisplatin binding to proteins.…”

Anticancer Applications and Recent Investigations of Metallodrugs Based on Gallium, Tin and Titanium

“…The 1,2-intrastrand d(GpG) cross-link is the major adduct. Binding of cisplatin to DNA causes significant distortion of the helical structure and results in inhibition of DNA replication and transcription ( Figure 2) [6]. The Pt 2+ unit covalently binds to deoxyribonucleic acid (DNA), particularly to the N7 of either guanine (G) or adenine (A) in the nucleotide sequences GG and AG to form interstrand cross-links [7] The so-formed cisplatin-DNA unit activates a new cellular pathway which leads to transcription inhibition, cell-cycle arrest, DNA repair, and finally apoptosis [8].…”

Antiproliferative Activity of Gold(III) Complexes with Esters of Cyclohexyl-Functionalized Ethylenediamine-N,N’-Diacetate

“…The two major problems associated with the use of cisplatin derivatives are the severe toxic side effects (11)(12)(13)(14)(15) and the intrinsic or acquired resistance manifested in various types of cancers (16). Therefore, in recent decades, a large number of new metal-based complexes have been developed and tested (17)(18)(19).…”