In Vitro Drug Repurposing: Focus on Vasodilators

Abstract

Drug repurposing aims to identify new therapeutic uses for drugs that have already been approved for other conditions. This approach can save time and resources compared to traditional drug development, as the safety and efficacy of the repurposed drug have already been established. In the context of cancer, drug repurposing can lead to the discovery of new treatments that can target specific cancer cell lines and improve patient outcomes. Vasodilators are a class of drugs that have been shown to have the potential to influence various types of cancer. These medications work by relaxing the smooth muscle of blood vessels, increasing blood flow to tumors, and improving the delivery of chemotherapy drugs. Additionally, vasodilators have been found to have antiproliferative and proapoptotic effects on cancer cells, making them a promising target for drug repurposing. Research on vasodilators for cancer treatment has already shown promising results in preclinical and clinical studies. However, additionally research is needed to fully understand the mechanisms of action of vasodilators in cancer and determine the optimal dosing and combination therapy for patients. In this review, we aim to explore the molecular mechanisms of action of vasodilators in cancer cell lines and the current state of research on their repurposing as a treatment option. With the goal of minimizing the effort and resources required for traditional drug development, we hope to shed light on the potential of vasodilators as a viable therapeutic strategy for cancer patients.

Targeting Transcription Factor YY1 for Cancer Treatment: Current Strategies and Future Directions

“…One example is nitroglycerin, which has shown promising results in lung cancer patients when used in combination with cisplatin, leading to improved response rates and longer time to progression [ 167 ]. Similarly, a clinical trial using slow-releasing nitroglycerine patches in men with high levels of prostate-specific antigen (PSA) after primary therapy resulted in a prolonged PSA doubling time, suggesting that nitric-oxide-induced inhibition of hypoxia-mediated progression may play a role in the observed therapeutic effects (NCT01704274) [ 168 ]. As a nitric oxide donor, nitroglycerin could inhibit NF-κB through S-nitrosylation, which could consequently interfere with NF-κB binding to DNA [ 169 , 170 ].…”

Understanding the Clinical Use of Levosimendan and Perspectives on its Future in Oncology

“…Previously, we evaluated the combination of levosimendan with 5-fluorouracil (5-FU), an antineoplastic drug, and found that this drug could help increase the cytotoxicity of 5-FU, decreasing the viability of bladder cancer cells [ 20 ].…”

“…This combination demonstrated a significantly greater reduction in cell viability compared to using the repurposed drug individually. Particularly noteworthy was the combination of 100 μM of levosimendan with the IC50 value of 5-FU (13.41 μM), which resulted in an impressive 59% decrease in cell viability compared to treating with 100 μM of levosimendan alone [ 20 ].…”

“…Moreover, the use of well-established drugs for purposes beyond their original intended use, such as vasodilators, is a new strategy for treating cancer. In a previous study [ 20 ], our group hypothesized that the use of levosimendan could enhance the cytotoxic effect of 5-fluorouracil (5-FU) in bladder cancer cells. The rationale behind this strategy is grounded in the fact that the toxicological profiles of the repurposed drugs are already well-documented and deemed safe.…”

Repurposing of the Drug Tezosentan for Cancer Therapy

“…Examples of vasodilators include drugs such as angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers, nitrates, PDE5 inhibitors, and endothelin antagonists, among others. These drugs work through different mechanisms to relax the smooth muscles in blood vessels, thereby reducing blood pressure and improving blood flow throughout the body [ 7 ].…”