Possible Interaction: Cisplatin and Vitamin B 6

“Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism as a central regulator of cisplatin responses in vitro and in vivo.”

“ Pyridoxine (vitamin B6) has been shown to reduce cisplatin and fluoropyrimidine-related neurotoxicity but its administration with OHP has not yet been studied.”

“The cell inactivating effect of cis-DDP was significantly reduced when the aldehyde analogs pyridoxal or pyridoxal 5'-phosphate were simultaneously present with cis-DDP.”

“Altogether, these results suggest that the combined regimen of cisplatin plus pyridoxine mediates immune-dependent antineoplastic effects against NSCLC.”

“Here, we evaluated the putative synergistic interaction of CDDP with pyridoxine in the treatment of an orthotopic mouse model of non-small-cell lung cancer (NSCLC).”

“Immunocompetent mice that had been cured from NSCLC by the combined regimen of CDDP plus pyridoxine became resistant against subcutaneous rechallenge with the same (but not with an unrelated) cancer cell line.”

“In vitro, CDDP and pyridoxine did not only cause synergistic killing of NSCLC cells but also elicited signs of immunogenic cell death including an endoplasmic reticulum stress response and exposure of calreticulin at the surface of the NSCLC cells.”

“NSCLC cells treated with CDDP plus pyridoxine in vitro elicited a protective anticancer immune response upon their injection into immunocompetent mice.”

“As a result, cisplatin resistance can be overcome by co-administration of pyridoxine , and cisplatin-resistant cancer cells become exquisitely sensitive to killing by inhibitors of poly(ADP-ribose) polymerase, starvation, and antimetabolites targeting nucleotide biosynthesis.”

“As a result, cisplatin and pyridoxine can be advantageously combined for the treatment of mice with lung cancers.”

“Importantly, pyridoxine does not only shift the dose response to cisplatin to lower levels with regard to apoptosis.”

“ Pyridoxine also enhances the efficacy of cisplatin with regard to the induction of the ER stress response, thereby improving the potential of the drug to trigger ICD (Figure ​(Figure1).1).”

“The synergistic interaction between cisplatin and pyridoxine is largely dependent on an adaptive anticancer immune response.”

“Accordingly, pyridoxine promoted the antineoplastic activity of CDDP in NSCLC-bearing mice only in the presence of an intact immune system.”

“We have recently demonstrated that pyridoxine , a precursor of vitamin B6, increases the immunogenicity of non-small cell lung carcinoma (NSCLC) cells succumbing to cisplatin (cis-diamminedichloroplatinum(II), CDDP).”

“This synergistic effect can be ascribed to the introduction of thermolabile sites by the combined action of cis-DDP and pyridoxal.”