Microbial amphiphiles: a class of promising new-generation anticancer agents

Abstract

Developing new classes of anticancer molecules has always been a major scientific challenge owing to multidrug resistance of cancer cells to conventional chemotherapeutic agents. Microbial amphiphiles, particularly lipopeptides and glycolipids, have recently emerged as potential new-generation anticancer agents, owing to low toxicity, high efficacy and easy biodegradability. They exhibit anticancer activities by retarding cell cycle progression, inhibiting crucial signaling pathways such as Akt, extracellular signal-regulated kinase/c-Jun N-terminal kinase (ERK/JNK) and Janus kinase/signal transducer and activator of transcription (JAK/STAT), reducing angiogenesis, activating natural killer T (NKT) cells and inducing apoptosis through death receptors in cancer cells. It has been well established that the oncogenic signals of cancer cells are amplified by the overexpression of various membrane-bound receptors such as Epidermal Growth Factor Receptor (EGFR), Vascular Endothelial Growth Factor Receptor (VEGFR), Platelet-derived Growth Factor Receptor (PDGFR) and Insulin-like Growth Factor Receptor (IGFR). Microbial amphiphiles, upon interaction with the cell membrane, are believed to suppress the activities of these cell surface receptors by fatty acid chain mediated membrane destabilization. This review analyzes the modes and mechanisms of action of these green molecules for application as potential anticancer agents.