Taxol, Camptothecin and Beyond for Cancer Therapy

Plants produce a remarkably diverse array of metabolites, many of which have evolved to confer effectiveness against microbial attack, resist environmental stress or function as signalling molecules in interplant communication. Further, botanical preparations have been used for treating and preventing various human diseases throughout history. More than half of the current anti-cancer drugs in clinical use are natural products or their derivatives, and many are plant-derived agents. Two renowned examples of plant-based drugs used for humans are paclitaxel and camptothecin (CPT). Paclitaxel (taxol), originally identified from Pacific yew Taxus brevifolia Nutt, and its semi-synthesized analogues docetaxel (Taxotere), and CPT, originally identified from Camptotheca acuminata Decne, a native tree to China, as well as its more water-soluble derivatives topotecan (Hycamtin) and irinotecan or CPT-11 (Camptosar), are used as chemotherapeutic drugs for various cancers. This review offers a current and integrative account of the two representative chemotherapeutic phytoagents paclitaxel and CPT in terms of their discovery, development of authentic compounds and improvement by synthetic chemistry approaches, as well as their mechanisms of action and clinical applications. We also discuss the bench-side or clinically observed drug resistance and adverse side effects of both drugs, which are the major drawbacks to their use for cancer. Despite intensive efforts and substantial advances in improving treatment, cancer is still a life-threatening and leading cause of death, especially with recurring, metastatic or drug-resistant tumours. The successful experiences with the discovery and development of paclitaxel and CPT as anti-cancer drugs have been significant milestones for the design of alternative strategies and remedies from plant-derived agents in cancer management.