Acid Ceramidase, a Double-edged Sword in Cancer Aggression: A Minireview

Abstract

Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway, hydrolyzes pro-apoptotic ceramide to sphingosine, which is metabolized to mitogenic sphingosine-1-phosphate by the action of sphingosine-1-kinase. The intracellular level of AC determines ceramide/ sphingosine-1-phosphate rheostat, which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased, and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy, thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.