Increased immune cell infiltration in patient-derived tumor explants treated with Traniplatin: an original Pt(iv) pro-drug based on Cisplatin and Tranilast

Abstract

Elevated intra-tumoral immune infiltrate is associated with an improved prognosis in cancer of distinct origins. Traniplatin (TPT) is a novel platinum(iv) pro-drug based on Cisplatin (CDDP) and the marketed drug Tranilast. When compared in vitro to Cisplatin, TPT showed increased cytotoxic activity against colon and lung cancer cells but decreased activity against immune cells. In addition, TPT efficiency was evaluated in tumor explants derived from colorectal cancer samples from patients subjected to intended curative surgery. TPT induced strong intra-tumoral cytotoxic activity yet was associated with an elevated presence of immune cell infiltrate, suggesting a reduced cytotoxic activity against immune cells in colorectal cancer.

Anti‐tumor platinum (IV) complexes bearing the anti‐inflammatory drug naproxen in the axial position

“…of ascorbic acid resulted in a strong signal for cisplatin at −2094 ppm. [34] Complex 1 was completely reduced after 3 hr of incubation with ascorbic acid at 37°C, in line with the HPLC analyses.…”

“…The 195 Pt-NMR spectra of 1 in D 2 O gave a quintet peak due to the spin to spin coupling between 195 Pt and two 14 N nuclei at 992 ppm, which is consistent with reported data. [34] These resonances were shifted downfield to 1170-1180 ppm in the dicarboxylato complexes (2-5; Figures S2-S5). The presence of an additional electron-withdrawing carboxylate ligand caused a greater deshielding effect on the platinum (IV) metal center in the dicarboxylato complexes than the monocarboxylato ones that cause the observed downfield shift on their 195 Pt-NMR resonances.…”

“…[28] Moreover, the axial coordination site can serve as a binding site for other biologically active ligands to form a single molecule that combines two biologically active compounds called dual-threat pharmaceutical agents. [29][30][31][32][33][34] On the other hand, a large number of studies have showed the effect of chronic inflammation in tumorgenesis, [35,36] and the role of using non-steroidal anti-inflammatory drugs (NSAIDs) as anti-cancer agents. [37][38][39][40] Although the use of NSAIDs can cause some problems, such as gastrointestinal bleeding and increased cardiovascular (CV) issues, [41] the anti-inflammatory drug naproxen ( Figure 1) has fewer CV effects with a possible cardioprotective role in humans.…”

Synthetic Lethality Screening Identifies FDA-Approved Drugs that Overcome ATP7B-Mediated Tolerance of Tumor Cells to Cisplatin

“…Tranilast inhibits the production of interleukin-6 and is normally used as an anti-allergic drug, which is well tolerated by most patients at very substantial doses [43]. Notably, a new compound based on cisplatin and Tranilast was developed recently and exhibited excellent cytotoxicity in tumor explants [44]. Telmisartan is also quite a safe agent, which operates as an angiotensin II receptor antagonist to treat hypertension [45].…”

Interfering in apoptosis and DNA repair of cancer cells to conquer cisplatin resistance by platinum(iv) prodrugs

“…20,21 This prodrug strategy has been widely used for the construction of multifunctional Pt complexes as illustrated in many studies. [22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38] BRCA and RAD51 play essential roles in HR, and BRCA-procient tumors are usually refractory to CDDP due to effective HR. Recently, we designed two Pt IV -artesunate prodrugs, which inhibited HR via downregulating RAD51 and exhibited higher cytotoxicity against BRCA-procient cancer cells than CDDP.…”