Nicotinamide pre-treatment reduced Cisplatin cytotoxicity in non-small cell lung cancer cell lines, likely due to thermodynamically favorable coordination with reactive Cisplatin species.
Does Nicotinamide interact with Cisplatin and modulate its cytotoxicity in non-small cell lung cancer cells?
Nicotinamide may interact with reactive Cisplatin species, potentially reducing its cytotoxicity and highlighting a potential drug-nutrient interaction in platinum-based chemotherapy.
Cisplatin remains a widely used anticancer agent; however, its effectiveness can be influenced by systemic toxicity, resistance mechanisms, and interactions with exogenous compounds. Nicotinamide (vitamin B3), an NAD+ precursor and a commonly used dietary supplement, is involved in cellular metabolism, redox homeostasis, and DNA repair pathways, which may potentially modulate the cellular responses to Platinum-based agents. Here, we combine chemical synthesis, computational studies, spectroscopic analysis, and biological assays to investigate the molecular and biological aspects of Cisplatin–Nicotinamide interactions. A novel cis-Pt(NH3)2NicotinamideClNO3 complex was obtained and its structure analyzed. Density functional theory (DFT) calculations indicate a thermodynamically favorable coordination of Nicotinamide to the first hydrolysis product of Cisplatin (CisPt1) with binding energies comparable to those calculated for nucleobase coordination under the same theoretical conditions. In non-small cell lung cancer cell lines (A549 and PC-9), in vitro results suggest that Nicotinamide pre-treatment reduces Cisplatin cytotoxicity under specific experimental conditions, but the pre-formed complex does not exert anticancer effects. These data are consistent with a model in which Nicotinamide may interact with reactive Cisplatin species, potentially contributing to the reduced availability of reactive Platinum(II) species. This work provides mechanistic insight into potential drug–nutrient interactions involving Platinum-based chemotherapy and highlights the need for further investigation under clinically relevant conditions in the near future.
Szefler et al. (Sat,) conducted a other in Non-small cell lung cancer (in vitro). Cisplatin and Nicotinamide was evaluated on Cisplatin cytotoxicity and molecular interactions. Nicotinamide pre-treatment reduced Cisplatin cytotoxicity in non-small cell lung cancer cell lines, likely due to thermodynamically favorable coordination with reactive Cisplatin species.