Abstract 4809: Monoethanolamine stimulates calcium-induced metabolic stress leading to autophagic cell death in prostate cancer

Abstract

Abstract Mitochondrial activity and metabolism are crucial to meet the energy demands of cancer cells. We have recently shown the efficacy of monoethanolamine (Etn), an orally deliverable lipid formulation, in reducing tumor growth in various xenograft models including prostate cancer (PCa). Etn increased the metabolic stress of PCa cells by depleting cellular glucose and glutamine levels. However, the precise mechanism of Etn-mediated metabolic stress in cancer cells remains elusive. Herein, we examined how Etn alters the activity and structure of the mitochondria to induce cell death. Etn treatment modulated phosphatidylethanolamine (PE) lipid and glycerophosphoethanolamine (GPE) levels in PCa cells. Altered PE lipids correlated with disruption of mitochondrial cristae and led to a concomitant accumulation of autophagosomes. Deregulated functional activity of mitochondria, as evidenced by reduced oxygen consumption rate (OCR), extracellular acidification rate (ECAR), were associated with structural distortions of the mitochondria and a transient increase in the intracellular calcium concentration. Etn treatment reduced the amount of cytosolic lipid droplets (LD) and caused a reduction in PE/GPE ratio. Further, we observed an increase in lipolysis and death-inducing autophagy activation in Etn-treated PCa cells. These data suggest that Etn is a promising anticancer agent for PCa and further studies to determine its efficacy in other cancer types are warranted. Citation Format: Chakravarthy Garlapati. Monoethanolamine stimulates calcium-induced metabolic stress leading to autophagic cell death in prostate cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 4809.