Molecular targets of celastrol in cancer: Recent trends and advancements

Despite the advancement in the well-equipped and sophisticated laboratories and facilities, cancer remains to be a major cause of death worldwide. Consequently, further investigation of novel strategies need to be evolved. Since the last few decades, the utilization of phytochemicals is emerging against several human cancers, including lung, breast, colon carcinoma, lymphoma, and other hematological malignancies. Terpenoids are a category of therapeutically active phytochemicals that have been utilized against cancer, cardiovascular and neurodegenerative disorders. Particularly, celastrol, a pentacyclic terpenoid, is well-studied for its variety of pharmacological properties. It is well documented that celastrol can modulate a variety of signaling pathways. Celastrol's anti-proliferative role has been found to be associated with its pro-apoptotic (via protein kinase B), anti-angiogenic (via vascular endothelial growth factor and vascular endothelial growth factor receptor), anti-metastatic (via matrix metalloproteinases), and anti-inflammatory (via cytokines and chemokines) activities. This review describes various molecular mechanisms of celastrol for understanding the biology of cancer initiation, progression as well as designing efficacious therapeutic strategies.