The effect of hyperthermia (42°C) on the anti-tumoral effect of bromelain, N-acetyl cysteine, chemotherapeutic agents and their combinations - an in vitro evaluation

Abstract

Bromelain, N-acetyl cysteine and their combinations show cytotoxicity at 37°C. Similarly, their combinations with common chemotherapeutic agents (gemcetabine, Mitomycin C, oxaliplatin and 5-FU) show enhanced cytotoxicity. Since, hyperthermia (42°C) inhibits cellular proliferation, we set out to determine if it would further enhance the effect of these agents. Tumour cells (pancreatic and colorectal) were grown in a 96 well plate and treated to various agents and their combinations at 37° and 42°C. The survival of cells at 72 hours was evaluated with sulfhordamine assay. Colony formation assay was performed to evaluate development of resistance to these agents and finally PAS staining was carried out to determine the effect of bromelain, Nacetylcysteine (NAC), oxaliplatin and their combinations on mucin secretion in ASPC-1 (pancreatic) cancer cells. Hyperthermia (42°C) enhanced cytotoxicity of certain agents or their combinations in some of the cell lines. It also showed the absence or a reduction of effect, with certain agents. Hyperthermia reduced colony formation in CFPAC cells and with agents (bromelain + NAC, gemcitabine, NAC + gemcitabine, Bromelain + NAC + Gemcitabine). A similar effect with 5FU, 5FU + NAC and 5FU + bromelain was observed. Hyperthermia reduced mucin secretion in ASPC-1 cells, with bromelain and its combinations with NAC and oxaliplatin. NAC as a single agent increased mucin with hyperthermia. The effect of hyperthermia on cytotoxicity of bromelain, NAC and their combinations with chemotherapeutic agents varied with agents, their combinations and cell types, showing an increase, null effect or a decrease. However, hyperthermia reduced colony formation and mucin secretion.