Berberine Synergistically Enhances Anticancer Activity of 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.

Berberine (BER), a botanical alkaloid, is purified from the roots and bark of the Berberis species. BER reportedly possesses multiple pharmacological properties, including anti-diarrheal, anti-fungal, anti‑diabetic, hepatoprotective and cardioprotective effects. BER also suppresses tumor growth through the induction of apoptosis and cell cycle arrest in cancer cells. Berberine has potential as a chemotherapy adjuvant due to its low toxicity and anticancer properties. This study attempted to investigate the synergistic anticancer efficacy of vincristine-berberine combination in vitro and in vivo with the purpose of reducing chemotherapeutic dose of vincristine and thereby circumventing the neuropathy associated with it.