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Does administration of isosorbide mononitrate affect cellular proliferation in oral squamous cell carcinoma? A
Ian P Downie1, Tijjani Umar, David J Boote
1Salisbury District Hospital, Wilts, UK.
Purpose:
There has been much interest in the role that the signaling molecule nitric oxide (NO) plays in cancer. NO has both tumor-promoting and tumor-inhibiting effects that are dependent on its local tissue concentration. In animal studies, the administration of exogenous NO has reduced both tumor growth and dissemination, and in vitro NO administration causes death of oral cancer cell lines. We evaluated the oral administration of the NO donor drug isosorbide mononitrate (ISMO) on cellular proliferation in patients with oral squamous cell carcinoma.
Materials And Methods:
A prospective randomized double-blind study was performed on 31 patients with biopsy-confirmed oral squamous cell carcinoma. Following incisional biopsy, patients were randomized to receive either ISMO (at a dose of 20 mg twice a day) or placebo tablets for 2 weeks before definitive resection. Cellular proliferation was compared between biopsy and resection specimens, using the immunohistochemical marker Ki-67.
Results:
No statistical difference was found between Ki-67 indices in initial biopsy and resection specimens after ISMO (P =.23) or placebo (P =.5) administration. There were no obvious clinical changes seen in the tumor during the clinical trial as a result of ISMO administration.
Conclusion:
Although high concentrations of NO are cytotoxic, it is unlikely that administration of NO at an increased dose would be useful in the management of oral cancer because this would result in unacceptable systemic side effects. The possible manipulation of NO in oral cancer is discussed.
Insights
Oral cancer patients receiving isosorbide mononitrate (ISMO), a nitric oxide (NO) donor, showed no significant change in cellular proliferation. This suggests NO therapy may not be effective for oral squamous cell carcinoma due to potential side effects.
Area of Science:
- Oncology
- Cancer Biology
- Pharmacology
Background:
- Nitric oxide (NO) has complex roles in cancer, exhibiting both tumor-promoting and inhibiting effects based on concentration.
- Exogenous NO administration has shown promise in reducing tumor growth and dissemination in animal models and inducing cell death in vitro.
- The potential of NO donors in cancer therapy warrants investigation, particularly in oral cancers.
Purpose of the Study:
- To evaluate the effect of orally administered isosorbide mononitrate (ISMO), an NO donor, on cellular proliferation in patients with oral squamous cell carcinoma.
- To determine if ISMO influences the proliferation marker Ki-67 in oral cancer tissues.
Main Methods:
- A prospective, randomized, double-blind study involving 31 patients with oral squamous cell carcinoma.
- Patients received either ISMO (20 mg twice daily) or placebo for 2 weeks prior to tumor resection.
- Cellular proliferation was assessed by comparing Ki-67 indices in biopsy and resection specimens.
Main Results:
- No statistically significant difference in Ki-67 indices was observed between biopsy and resection specimens in either the ISMO or placebo groups.
- Oral administration of ISMO did not lead to apparent clinical changes in tumor size or appearance during the trial.
- The study found no evidence that ISMO impacts cellular proliferation in oral squamous cell carcinoma under the tested conditions.
Conclusions:
- Increased nitric oxide (NO) dosage is unlikely to be beneficial for managing oral cancer due to the risk of unacceptable systemic side effects.
- The study highlights the complex role of NO in cancer and suggests limitations for NO-based therapies in oral squamous cell carcinoma.
- Further research into the nuanced manipulation of NO pathways in oral cancer treatment is warranted.
