Background: Pineapple was traditionally used as a folk medicine to cure different ailments by the aboriginal inhabitants of Central and South America and its extract derived from the stem and juice of the plant, called bromelain, was first manufactured as a pharmaceutical product in 1956.1 Through interaction with a variety of physiological pathways and processes, bromelain has shown efficacy in a number of inflammatory and auto-immune diseases, cardiovascular and respiratory disorders, musculoskeletal injuries, genitourinary conditions, infections and malignancies.2 In the present study, cytotoxic effects of bromelain on four different cancer cell lines of gastrointestinal origin have been investigated.
Methods: Two human gastric carcinoma cell lines (KATO-III and MKN45) and two chemoresistant sub-populations of human colon adenocarcinoma cell line HT29 (HT29-5M21 and HT29-5F12) were treated with a range of concentrations of bromelain. The effect of bromelain on the growth and proliferation of the cancer cells was determined after 72 hours of treatment using Sulforhodamine B (SRB) assay. Moreover, the expression of apoptosis-associated proteins in MKN45 cells treated with bromelain was analysed by western blotting.
Results: Bromelain inhibited proliferation of HT29-5F12, HT29-5M21, MKN45 and KATO-III cells with IC50 values of 0.030, 0.034, 0.094 and 0.142 mg/ml, respectively. Western blot analysis of a number of proteins involved in apoptosis revealed that bromelain activated apoptotic pathways. This was observed as altered caspases 3, 8 and 9, cleavage of PARP and p53, increased cytochrome-C, decreased bcl-2 and phospho-Akt, and removal of MUC-1, collectively indicating dose-dependent apoptosis with involvement of both intrinsic and extrinsic pathways.
Conclusion: We report for the first time the bromelain-induced cytotoxicity in the gastric and colon carcinoma cells studied.