Chemosensitizing efficacy of curcumin in paclitaxel chemotherapy as evidenced by chemical-induced and xenograft models of cervical cancer
Ruby John Anto Integrated Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India, 695014
Abstract:
Paclitaxel is the most potent antineoplastic drug ever been isolated from plants. However, dose limiting toxicity and drug resistance remain as major obstacles in its clinical application. Innovation of strategies that can overcome chemoresistance can enhance its therapeutic efficacy. We have previously shown that curcumin, a natural polyphenol, enhances paclitaxel-induced cytotoxicity in vitro through down-regulation of NF-κB and Akt pathways. The present study was conducted to verify whether this synergism exists in vivo and to elucidate the underlying molecular mechanisms. Multistage squamous cell carcinoma was induced in the uterine cervix of Swiss albino mice using 3-methylcholanthrene to evaluate the synergistic anticancer effect of paclitaxel and curcumin. The synergism was also elucidated in a xenograft tumor model of human cervical cancer in NOD-SCID mice. The results proves that curcumin augments the chemotherapeutic efficacy of paclitaxel by down-regulating the survival signals such as NF-κB, Akt and MAPKs that play key roles in proliferation, survival, angiogenesis and metastasis. We also observed that pre-exposure of carcinoma cells isolated from 3-MC-induced tumors to curcumin potentiates paclitaxel-induced apoptosis. Taken together, the findings of this preclinical study provide a strong rationale for the validation of this combination through clinical trials, which may be beneficial to cancer patients.
