Acid Ceramidase: A Novel Therapeutic Target in Cancer
Sphingolipids are important constituents of the eukaryotic cell membrane which govern
various signaling pathways related to different aspects of cell survival. Ceramide and Sphingosine are
interconvertible sphingolipid metabolites, out of which Ceramide is pro-apoptotic and sphingosine is
anti-apoptotic in nature. The conversion of ceramide to sphingosine is mediated by Acid Ceramidase
(ASAH1) thus maintaining a rheostat between a tumor suppressor and a tumor promoter. This rheostat
is completely altered in many tumors leading to uncontrolled proliferation. This intriguing property of
ASAH1 can be used by cancer cells to their advantage, by increasing the expression of the tumor promoter,
sphingosine inside cells, thus creating a favorable environment for cancer growth. The different
possibilities through which this enzyme serves its role in formation, progression and resistance of different
types of cancers will lead to the possibility of making Acid Ceramidase a promising drug target.
This review discusses the current understanding of the role of acid ceramidase in cancer progression,
metastasis and resistance, strategies to develop novel natural and synthetic inhibitors of ASAH1 and
their usefulness in cancer therapy.
Journal Title: Current Topics in Medicinal Chemistry