Berberine Synergistically Enhances Anticancer Activity of the Vincristine in Vitro and in Vivo

Vinca alkaloids isolated from the periwinkle plant, Vinca rosea Linn. like vincristine (VCR) and vinblastine have proved to be the most active antitumor agents. VCR has been widely used in the treatment of many neoplastic diseases, including the non- Hodgkin’s and Hodgkin’s lymphomas, ALL, breast carcinoma, Wilms’ tumor, neuroblastoma, and embryonal rhabdomyosarcoma, etc. The major antitumor effect of this agent appears to be related to its high-affinity binding to the basic protein subunit of microtubules, tubulin, which results in disruption of the mitotic spindle apparatus and arrest of cells in metaphase. VCR also binds to neuronal tubulin, disrupting axonal microtubules and resulting in neurotoxicity, therefore limiting the maximum clinical dose of VCR to 2.0 mg regardless of body surface area. Thus, vincristine neurotoxicity is major limitation in successful treatment of cancer that negatively impacts quality of life of cancer patients.