Natural Products and Small Molecules Targeting Cellular Ceramide Metabolism to Enhance Apoptosis in Cancer Cells

Abstract

Molecular targeting strategies have been used for years in order to control cancer progression and are often based on targeting various enzymes involved in metabolic pathways. Keeping this in mind, it is essential to determine the role of each enzyme in a particular metabolic pathway. In this review, we provide in-depth information on various enzymes such as ceramidase, sphingosine kinase, sphingomyelin synthase, dihydroceramide desaturase, and ceramide synthase which are associated with various types of cancers. We also discuss the physicochemical properties of well-studied inhibitors with natural product origins and their related structures in terms of these enzymes. Targeting ceramide metabolism exhibited promising mono- and combination therapies at preclinical stages in preventing cancer progression and cemented the significance of sphingolipid metabolism in cancer treatments. Targeting ceramide-metabolizing enzymes will help medicinal chemists design potent and selective small molecules for treating cancer progression at various levels.

Hepatotoxicity assessment of innovative nutritional supplements based on olive-oil formulations enriched with natural antioxidants

“…Certain genes, including ASAH1, FASN, HYOU1, and ACTB, exhibit exclusive upregulation in response to Formulations, indicating a nuanced regulatory response to the different compositions. ASAH1, encoding acid ceramidase, plays a crucial role in sphingolipid metabolism by hydrolyzing ceramide into sphingosine and fatty acid, thereby influencing cellular processes such as apoptosis, cell growth, and inflammation ( 45–47 ). HYOU1, functions as a molecular chaperone under hypoxic and endoplasmic reticulum (ER) stress conditions, modulates protein folding and cell survival, although limited literature exists on natural products influencing HYOU1 upregulation ( 48–50 ).…”

Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology

“…These inhibitors, most of which are natural products, have been extensively used in basic research to study the complex intricate biology of sphingolipids and understand reaction mechanisms. More importantly, they hold significant promise for therapeutic interventions in a range of diseases, including cancer, LSDs, immune system dysfunctions, and neurodegenerative diseases ( Bu et al, 2021 ; Afrin et al, 2023 ).…”