Effects of bafilomycin A1, a vacuolar type H+ ATPase inhibitor, on the thermosensitivity of a human pancreatic cancer cell line.

Abstract

PURPOSE:

It has been known that the thermosensitivity of tumour cells can be increased by lowering intra-cellular pH (pHi) by inhibiting pHi control mechanisms. The pHi is partially controlled by transport of H+ from cytoplasm into endocytic and secretary systems in the cells mediated by vacuolar type H+ATPase and also by transport of H+ through plasma membrane.

METHODS:

This study investigated the effects the bafilomycine A1, an inhibitor of the vacuolar type H+ATPase and the EIPA, an inhibitor of the Na+/H+ exchanger in plasma membrane, on thermosensitivity of AsPC-1 cells, a human pancreatic cancer cell line. It also investigated the effects of combination of bafilomycine A1 and EIPA.

RESULTS:

The treatment of cancer cells with bafilomycine A1 or EIPA individually slightly lowered pHi of the cells in vitro and increased the thermosensitivity of the cells.

CONCLUSION:

The combination of these two drugs significantly lowered pHi and increased thermosensitivity of cancer cells in vitro and enhanced the heat-induced the growth delay of AsPC-1 tumours grown s.c in the legs of BALB/cA nude mice.

• Authors: Yasuo Hayashi, Kanji Katayama, Tamotsu Togawa, Toshihisa Kimura, Akio Yamaguchi
• Journal: International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group (Int J Hyperthermia) Vol. 22 Issue 4 Pg. 275-85 (Jun 2006) ISSN: 0265-6736 [Print] England
• PMID: 16754349 (Publication Type: Journal Article)

Chemical References

• Enzyme Inhibitors
• Macrolides
• Sodium-Hydrogen Exchangers
• Amiloride
• bafilomycin A1
• Proton-Translocating ATPases
• ethylisopropylamiloride

Topics

• Amiloride (analogs & derivatives, pharmacology)
• Animals
• Antineoplastic Combined Chemotherapy Protocols
• Body Temperature Regulation (drug effects, physiology)
• Cell Line, Tumor
• Cell Membrane (drug effects, physiology)
• Combined Modality Therapy
• Enzyme Inhibitors (pharmacology)
• Humans
• Hydrogen-Ion Concentration
• Hyperthermia, Induced
• Macrolides (pharmacology)
• Male
• Mice
• Mice, Nude
• Pancreatic Neoplasms (physiopathology, therapy)
• Proton-Translocating ATPases (antagonists & inhibitors)
• Sodium-Hydrogen Exchangers (antagonists & inhibitors)
• Transplantation, Heterologous (pathology)