Multifunctional pentacyclic triterpenoids as adjuvants in cancer chemotherapy: a review

Abstract

Chemotherapeutic agents are a mainstay in the treatment of cancer. However, the nonselectivity of cytotoxic anticancer agents results in multiorgan toxicities. Cancer chemotherapy is often associated with toxicities, which can be expensive to manage and may affect the patient quality of life. Very few organ-protective agents like amifostine are proved as adjuvants to cancer chemotherapy. Amifostine protects against a wide range of chemo- and radiotherapy-related toxicities and reduces costs of supportive care. Multifunctional natural compounds like pentacyclic triterpenoids and their semisynthetic derivatives possess organ-protective activities against drug-induced toxicities. Triterpenoids interact with biomolecules involved in the cytotoxicity of chemotherapeutic agents. They also sensitize cancer cells for cytotoxic effect of chemotherapy. Further, pentacyclic triterpenoids themselves possess anticancer activity. The efficacy of pentacyclic triterpenoids as organotropic, anticancer and chemo sensitizers may prove these agents as adjuvant to cancer chemotherapy. The current review focuses on the systematic studies of the multifunctional role of pentacyclic triterpenoids and their derivatives in chemotherapy. Interactions of pentacyclic triterpenoids with molecular targets like nuclear factor erythroid-derived 2-like 2 (NrF2), nuclear factor kappa B (NFκ-B), protein kinase C (PKC), free radical scavenging, and cell longevity pathways that contribute to cytoprotective, anticancer, chemosensitizer and chemopreventive effects have been emphasized. The therapeutic utility of pentacyclic triterpenoids as multifunctional adjuvants in cancer chemotherapy is highlighted.