Dolastatins and their analogues present a compelling landscape of potential natural and synthetic anticancer drug candidates

Abstract

Human cancer remains a leading cause of global mortality. Traditional treatment methods, while effective are often associated with substantial side effects, high technical requirements, and considerable expenses. Recently, anticancer peptides, such as dolastatin-type peptides naturally found in marine mollusc Dolabella auricularia, have gained attention due to their enhanced characteristics and specific targeting of cancer cells with minimal toxicity to normal cells. This review aims to provide a comprehensive summary of the anticancer activities of natural dolastatins and synthetic analogues over the past 35 years, focusing on their utilization in advancing cancer treatment strategies. This updated review encompasses a detailed analysis of numerous studies demonstrating the cytotoxic effects of dolastatins and their synthetic analogues on various human tumour cell lines. The analysis includes investigations into their ability to activate apoptosis pathways, inhibit cell cycle progression, and indirectly limit inflammation and angiogenesis in tumours. Both natural dolastatins and synthetic analogues have demonstrated significant anticancer properties through a variety of mechanisms in vitro and in vivo pharmacological studies. Some have even advanced to clinical trials, either alone or in combination with other agents, and have shown promising outcomes. The biological activities of dolastatins and their synthetic analogues offer a promising path in the development of more effective and sustainable anticancer drugs. Their specific action on cancer cells and relative non-toxicity to normal cells highlight their potential as superior cancer therapeutic agents. The current study provides a platform for the most recent preclinical and clinical research on dolastatins and their analogues. Further research into these marine peptides may contribute to the development of sustainable and efficient treatment models for cancer, filling a significant gap in the current cancer therapeutic portfolio.

Keywords

• Dolastatins
• Synthetic analogues
• Anticancer activity
• Marine-derived compounds
• Apoptosis
• Cytotoxicity