Malaysian Journal of Biochemistry
& Molecular Biology
(E-ISSN: 2600-9005)
The Official Publication of the Malaysian Society for Biochemistry & Molecular Biology (MSBMB)
Indexed by SCOPUS and Malaysian Citation Index (MYCITE)
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April
Malay. J. Biochem. Mol. Biol. (2026) 29 (1)
Page range 1-130
Regular Article
DOI:
Page 57-79
Mriganka Mandal, Jishu Mandal, Sourav Pakrashy and Amrita Basak
SPHINGOLIPID METABOLISM AND CERAMIDE AS A KEY INTER PLAYER FOR MALIGNANT CELL DEATH: INSIGHT MOLECULAR STUDY AND THERAPEUTIC EFFICACY
Abstract
Lipids, particularly sphingolipids, are key biomolecules responsible for numerous cellular processes in mammalian cells. Sphingolipids influence a wide range of functions, including cell proliferation, differentiation, adhesion, motility, and death. Their metabolism activates various signaling pathways, many of which are directly associated with the anti-tumorigenic apoptotic pathway. Ceramide, the central metabolite of sphingolipids, has been extensively studied in recent decades. Evidence shows that chemotherapeutic drugs and radiation therapy increase endogenous ceramide levels, thereby inducing malignant cell death through multiple death-signaling pathways. Other sphingolipid derivatives, such as gangliosides and sphingosine-1-phosphate, also play pivotal roles in diverse cellular functions. Malignant cell death initiated by sphingolipids has been demonstrated in various cell lines, and sphingolipid metabolism is increasingly recognized as a promising target for therapeutic intervention. This review highlights the molecular pathways of ceramide-induced cell death, emphasizing both intrinsic and extrinsic apoptotic mechanisms. Since ceramide is composed of sphingosine and a fatty acid, its metabolism and related signaling cascades provide important insights into anti-tumour activity. A deeper understanding of the molecular basis of ceramide action may enhance knowledge of disease pathogenesis and support the development of novel therapeutic strategies. Here, we also summarize the diverse functional roles of sphingolipid metabolism in malignant cell death and the associated signaling pathways.