New mechanisms for old drugs: Insights into DNA-unrelated effects of platinum compounds and drug resistance determinants

p62/SQSTM1 as an oncotarget mediates cisplatin resistance through activating RIP1‐NF‐κB pathway in human ovarian cancer cells

“…Recently, investigators have paid more attention to these "nonnuclear" effects and the molecular pathways that are involved in the cell survival and apoptotic escape. (3) Our previous study showed that sequestosome-1 (p62/SQSTM1) was highly expressed in cisplatin-resistant ovarian cancer cells. Furthermore, resistance to Pt was removed when we inhibited the p62 expression with the siRNA.…”

“…Since the 1970s, tolerance to Pt has been blamed on effects unrelated to DNA damage. Recently, investigators have paid more attention to these “non‐nuclear” effects and the molecular pathways that are involved in the cell survival and apoptotic escape . Our previous study showed that sequestosome‐1 (p62/SQSTM1) was highly expressed in cisplatin‐resistant ovarian cancer cells.…”

Unexpected Growth-Promoting Effect of Oxaliplatin in Excision Repair Cross-Complementation Group 1 Transfected Human Colon Cancer Cells

“…The cytotoxicity of these compounds is due to the interaction with DNA and the formation of DNA-platinum adducts, with the subsequent induction of apoptosis [3]. Recently reviewed results also strongly suggest more complex mechanisms involved in this cytotoxicity, such as the interaction with mitochondria and with the immunologic tumour environment [4]. Several resistance mechanisms have been proposed to be involved in a decreased clinical response to platinum derivatives, such as modified expression of membrane copper transporters [5], increased inactivation of intracellular platinum derivatives by glutathione [6], defects in the apoptotic machinery [7] or increased repair activity on the DNA adducts [8,9].…”

Study of the cytotoxic and genotoxic potential of the carbonyl ruthenium(II) compound, ct‐[RuCl(CO)(dppb)(bipy)]PF6 [dppb = 1,4‐bis(diphenylphosphino)butane and bipy = 2,2′‐bipyridine], by in vitro and in vivo assays

“…Classical anticancer drugs inhibit cell replication and transcription through the direct or indirect interaction with DNA, and induce mutagenic, cytotoxic, genotoxic and carcinogenic effects (Chen, Chang, & Cheng, ; Fonseca et al, ; Lin et al, ). For example the platinum‐based drugs such as cisplatin and other square‐planar platinum analogs (carboplatin and oxaliplatin), which, despite their success as chemotherapeutics, cause renal failure and nephrotoxicity, peripheral neuropathy, hepatic toxicity, myelotoxicity, gastrointestinal toxicity, ototoxicity, hematological toxicity and drug resistance (Bergamo et al, ; Brock et al, ; Gatti, Cassinelli, Zaffaroni, Lanzi, & Perego, ; Grozav et al, ; Keppler, Berger, & Heim, ; Mengoli, Parmeggiani, Mengoli, Grinzi, & Tolomelli, ; Muggia, ; Quasthoff & Hartung, ). Treatment with these drugs is therefore limited.…”