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Repurposing Kir6/SUR2 Channel Activator Minoxidil to Arrests Growth of Gynecologic Cancers
Daniela Fukushiro-Lopes1, Alexandra D Hegel1,2, Angela Russo3
1Department of Pharmacology, Loyola University Chicago, Maywood, IL, United States.
Abstract:
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.
Insights
Targeting Kir6.2/SUR2 potassium channels with minoxidil shows promise for gynecologic cancers. This approach may offer a safe, new treatment option alongside chemotherapy by disrupting cancer cell metabolism and causing DNA damage.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Gynecologic cancers represent a significant health challenge, particularly in advanced stages.
- Ion channels play crucial roles in cellular functions and are emerging as potential cancer therapeutic targets.
- The specific role of ion channel modulation in gynecologic cancers remains largely unexplored.
Purpose of the Study:
- To investigate the prognostic significance of the Kir6.2/SUR2 potassium channel in gynecologic cancers.
- To evaluate the anti-tumor effects of pharmacological stimulation of the Kir6.2/SUR2 channel using minoxidil.
- To elucidate the underlying mechanisms by which minoxidil affects cancer cell viability.
Main Methods:
- Analysis of Kir6.2/SUR2 potassium channel expression as a prognostic factor.
- In vivo studies using a xenograft ovarian cancer model treated with minoxidil.
- Assessment of cellular and molecular changes, including metabolic state, mitochondrial function, DNA damage, and cell death pathways.
Main Results:
- Kir6.2/SUR2 potassium channel expression was identified as a favorable prognostic indicator in gynecologic cancers.
- Minoxidil treatment significantly inhibited tumor growth in an ovarian cancer xenograft model.
- Minoxidil induced mitochondrial disruption, DNA damage, and caspase-3 independent cell death in cancer cells.
Conclusions:
- The Kir6.2/SUR2 potassium channel is a potential prognostic marker for gynecologic cancers.
- Pharmacological activation of Kir6.2/SUR2 channels with minoxidil demonstrates anti-tumor efficacy.
- Repurposing FDA-approved potassium channel activators could offer a novel, safe adjuvant therapy for gynecologic cancers.
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