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Updated: May 10, 2026
11:56
A Rapid and Specific Microplate Assay for the Determination of Intra- and Extracellular Ascorbate in Cultured Cells
Published on: April 11, 2014
Ascorbic acid derivatives as a new class of antiproliferative molecules
Benoit Bordignon1, Julien Chiron, Michel Fontés
1Therapy of Genetic Disorders, EA 4263, Aix-Marseille Université (AMU), Faculté de Médecine, 27 Boulevard Jean Moulin, F-13385 Marseille, France.
Cancer Letters
|June 25, 2013
Summary
New ascorbic acid (AA) derivatives show potent antiproliferative and cytotoxic effects against cancer cells. These compounds, like K873, are effective at lower concentrations and selectively target tumors, offering a promising new avenue for cancer therapy.
Area of Science:
- Biochemistry
- Oncology
- Pharmacology
Background:
- Ascorbic acid (AA) exhibits antiproliferative properties but requires high concentrations and intravenous administration.
- Achieving sustained high concentrations of AA in vivo is challenging due to physiological regulation.
- Existing limitations necessitate the development of more effective and manageable therapeutic agents.
Purpose of the Study:
- To investigate novel ascorbic acid (AA) derivatives as potential anti-cancer agents.
- To evaluate the antiproliferative and cytotoxic efficacy of these derivatives compared to AA.
- To assess the selective toxicity and in vivo anti-tumor activity of a lead compound.
Main Methods:
- Synthesis and screening of AA derivatives for anti-cancer activity.
- Determination of IC50 values for lead compounds against various human tumor cell lines.
- In vitro assessment of selective toxicity towards cancer versus normal cells.
- In vivo efficacy studies using xenografted immunodeficient mice treated with K873.
- Gene expression analysis (microarrays) to elucidate mechanisms of action.
Main Results:
- AA derivatives demonstrated significantly lower IC50 values than AA itself.
- K873 exhibited potent cytotoxic and antiproliferative effects on human tumor cells at micromolar concentrations.
- K873 selectively killed cancer cells while sparing normal, poorly dividing cells.
- K873 treatment in vivo markedly inhibited tumor progression in xenograft models.
- K873 reduced the expression of key cell cycle-related genes (translation initiation factors, tRNA synthetases) in tumors, similar to AA.
Conclusions:
- AA derivatives, exemplified by K873, represent a promising new class of anti-cancer drugs.
- K873 displays selective anti-tumor activity and inhibits tumor progression in vivo.
- The mechanism of action for K873 appears to involve downregulating genes critical for cell cycle progression, similar to AA.
- These findings support the potential of AA derivatives as monotherapy or combination therapy for cancer treatment.
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