Selective Toxicity of Weak Organic Acids in Tumors
Author Information
Author(s): A.R. Karuri, E. Dobrowsky, I.F. Tannock
Primary Institution: Ontario Cancer Institute and University of Toronto
Hypothesis
Can organic acids cause acidification and death of cells at low pHe, and are these effects increased by agents that inhibit pHi regulation?
Conclusion
Weak acids can cause selective cellular acidification and toxicity at low pHe in culture, but their effectiveness in vivo is limited by low achievable concentrations.
Supporting Evidence
- Weak acids caused intracellular acidification of murine EMT-6 and human MGH-Ul cells in a concentration and pHe dependent manner.
- At low pHe (<6.5), weak acids caused in vitro cytotoxicity to these cells.
- Acid-dependent cytotoxicity was enhanced by exposure to Na+/H+ exchange inhibitors.
Takeaway
Weak acids can make cancer cells sick by making them too acidic, but they don't work well in real patients because there isn't enough of them in the body.
Methodology
The study evaluated the effects of weak organic acids on cellular acidification and cytotoxicity in murine and human cancer cell lines under varying pH conditions.
Limitations
The low concentrations of weak acids achievable in vivo limit their potential therapeutic effects.
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