Repurposing Kir6/SUR2 Channel Activator Minoxidil to Arrests Growth of Gynecologic Cancers
| Autor: | Joanna E. Burdette, Margaret Liotta, Vitalyi Senyuk, Gyda C. Beeson, Angela Russo, Craig Beeson, Daniela Fukushiro-Lopes, Alexandra D. Hegel, Ronald K. Potkul, Saverio Gentile |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Programmed cell death repurposing drug medicine.medical_treatment minoxidil Cellular homeostasis cancer treatment 03 medical and health sciences 0302 clinical medicine medicine oxidative stress Pharmacology (medical) Original Research Pharmacology Chemotherapy Activator (genetics) business.industry lcsh:RM1-950 ion channels medicine.disease Potassium channel mitochondria 030104 developmental biology lcsh:Therapeutics. Pharmacology Minoxidil 030220 oncology & carcinogenesis Cancer cell Cancer research Ovarian cancer business medicine.drug |
| Zdroj: | Frontiers in Pharmacology, Vol 11 (2020) Frontiers in Pharmacology |
| ISSN: | 1663-9812 |
| Popis: | Gynecologic cancers are among the most lethal cancers found in women, and, advanced stage cancers are still a treatment challenge. Ion channels are known to contribute to cellular homeostasis in all cells and mounting evidence indicates that ion channels could be considered potential therapeutic targets against cancer. Nevertheless, the pharmacologic effect of targeting ion channels in cancer is still understudied. We found that the expression of Kir6.2/SUR2 potassium channel is a potential favorable prognostic factor in gynecologic cancers. Also, pharmacological stimulation of the Kir6.2/SUR2 channel activity with the selective activator molecule minoxidil arrests tumor growth in a xenograft model of ovarian cancer. Investigation on the mechanism linking the Kir6.2/SUR2 to tumor growth revealed that minoxidil alters the metabolic and oxidative state of cancer cells by producing mitochondrial disruption and extensive DNA damage. Consequently, application of minoxidil results in activation of a caspase-3 independent cell death pathway. Our data show that repurposing of FDA approved K+ channel activators may represent a novel, safe adjuvant therapeutic approach to traditional chemotherapy for the treatment of gynecologic cancers. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|