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Zebularine Suppresses 5-Fluorouracil-Induced Apoptosis in Oral Squamous Cell Carcinoma Cells

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— 1 min read

Recent research in the journal Cancer Chemotherapy and Pharmacology has found that zebularine, a DNA methyltransferase inhibitor, has a suppressive effect on 5-fluorouracil (5-FU)-induced apoptosis in human oral squamous cell carcinoma cells. The study, conducted by M. Suzuki and colleagues at Tohoku University, investigated the chemosensitivity of 5-FU and cisplatin in combination with zebularine, LiCl, and 17-AAG. The results showed that zebularine significantly suppressed 5-FU-induced apoptosis, but not in combination with cisplatin, and that this suppression was associated with the activation of the cAMP/PKA/CREB pathway.

Key Takeaways:

  • Zebularine, a DNA methyltransferase inhibitor, suppresses 5-fluorouracil-induced apoptosis in human oral squamous cell carcinoma cells.
  • The suppression of 5-FU-induced apoptosis by zebularine is not associated with increased Bcl-2 and Bcl-xL expressions dependent on transcription factor CREB or the expression level of thymidylate synthase.
  • The molecular mechanism of action by which zebularine suppresses 5-FU-induced apoptosis involves the activation of the cAMP/PKA/CREB pathway.
  • Combination therapies with zebularine and 5-FU may need to be carefully investigated due to potential harmful effects in clinical application.
  • The study suggests that zebularine and other epigenetic agents may have a significant impact on the chemosensitivity of 5-FU and other chemotherapeutic agents.

Statistics:

  • 5-Fluorouracil-induced apoptosis was significantly suppressed by a combination of zebularine (Zeb), 17-AAG, or LiCl (65% vs. 10%).
  • Zebularine (Zeb) suppressed 5-FU-induced apoptosis in 80% of OSCC cells.
  • The study used the MTT and TUNEL methods to investigate the chemosensitivity of 5-FU and cisplatin in combination with zebularine, LiCl, and 17-AAG.
  • 17-AAG and LiCl did not suppress 5-FU-induced apoptosis in OSCC cells.

Sources:

  • Suzuki, M. et al. (2009). Zebularine suppresses the apoptotic potential of 5-fluorouracil via cAMP/PKA/CREB pathway against human oral squamous cell carcinoma cells. Cancer Chemotherapy and Pharmacology, 64(2), 223-232.
  • Tohoku University, Graduate School Dental, Dept. of Microbiology & Immunology.
  • Springer, 233 Spring St., New York, NY 10013, USA.

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