Cancers, Vol. 12, Pages 2576: Amino Acids Regulate Cisplatin Insensitivity in Neuroblastoma

Cancers, Vol. 12, Pages 2576: Amino Acids Regulate Cisplatin Insensitivity in Neuroblastoma Cancers doi: 10.3390/cancers12092576 Authors: Venugopal Gunda Anup S. Pathania Srinivas Chava Philip Prathipati Nagendra K. Chaturvedi Don W. Coulter Manoj K. Pandey Donald L. Durden Kishore B. Challagundla Neuroblastoma are pediatric, extracranial malignancies showing alarming survival prognosis outcomes due to their resilience to current aggressive treatment regimens, including chemotherapies with cisplatin (CDDP) provided in the first line of therapy regimens. Metabolic deregulation supports tumor cell survival in drug-treated conditions. However, metabolic pathways underlying cisplatin-resistance are least studied in neuroblastoma. Our metabolomics analysis revealed that cisplatin-insensitive cells alter their metabolism; especially, the metabolism of amino acids was upregulated in cisplatin-insensitive cells compared to the cisplatin-sensitive neuroblastoma cell line. A significant increase in amino acid levels in cisplatin-insensitive cells led us to hypothesize that the mechanisms upregulating intracellular amino acid pools facilitate insensitivity in neuroblastoma. We hereby report that amino acid depletion reduces cell survival and cisplatin-insensitivity in neuroblastoma cells. Since cells regulate their amino acids levels through processes, such as autophagy, we evaluated the effects of hydroxychloroquine (HCQ), a terminal autophagy inhibitor, on the ...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research