Objective: Gemcitabine (GEM) is commonly chosen for treating pancreatic cancer. However, its use is limited by toxicity. Earlier in vitro studies with GEM in combination with Bromelain (Brom) and Acetylcysteine (Ac) indicated a substantial reduction in IC50. Here, we investigated the efficacy and safety of Brom and Ac (BromAc) in the pancreatic cancer model in vivo. Design: Both low dose and high dose studies for safety and efficacy of BromAc and GEM were conducted in nude mice. Body weight,

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... lbeing and tumor volume were monitored. At autopsy, tumor weight, tumor density, percentage of tumor necrosis, expression of Ki67 antigen, and immunohistological evaluation of vital organs were compared between the treatment groups. Results: The low and high doses of BromAc alone and with chemotherapy agents were safe. A very significant reduction in pancreatic tumor volume, weight, and ki67 were seen with BromAc therapy and was equal to treatment with GEM alone and better than treatment with 5-FU. In addition, tumor density was significantly reduced by BromAc. Conclusion: These encouraging results are the first in vivo evidence of the efficacy of BromAc in pancreatic cancer and provide some mechanistic leads.