Journal of Stem Cell Research & Therapy

Pharmacological modulation of the mitochondrial potassium channel KV1.3 triggers apoptosis of cancer stem cells and prevents mammosphere formation

7^th International Conference and Expo on Cell and Stem Cell Research

June 28, 2023 | Webinar

Gayathri Viswanathan, Luca Menilli, Magdalena Bachmann, Greta Avancini, Tatiana Varanita, Vanessa Checchetto, Francesca Moret and Ildiko Szabo

University of Padova, Padova, Italy

Posters & Accepted Abstracts: J Stem Cell Res Ther

Abstract:

Triple Negative Breast Cancer (TNBC) is a heterogenous, recurring cancer with a high rate of metastasis, poor prognosis and lack of therapeutic targets. Various murine and human TNBC cells express high level of the mitochondrial Kv1.3 ion channel. Therefore, we investigated the effects of Kv1.3 inhibitors that are either membrane-impermeant and act on the plasma membrane-located channels, or two inhibitors that act on the mitochondria-located channel. These latter inhibitors, PAPTP and PCARBTP, were able to trigger apoptosis in 2D TNBC cultures by altering the mitochondrial function and leading to reactive oxygen species release. Gemcitabine acted synergistically with PAPTP and PCARBTP. These modulators at sublethal doses were very efficient in 3D mammosphere models, developed with both murine and mammalian TNBC cells as well, while membrane-impermeant toxin inhibitors of Kv1.3 were without effect. The efficiency of PAPTP and PCARTP to inhibit mammosphere formation was increased in combination treatment with gemcitabine. The combination treatment abolished CSC population in the mammospheres, as confirmed by advanced Aldefluor assay. Further biochemical experiments highlighted that PAPTP in combination with gemcitabine affected cellular pathways that are crucial for cancer stemness potential. Overall, our results show that mitochondrial Kv1.3 inhibitors along with gemcitabine are promising agents against TNBC as they efficiently impair mammosphere formation.

Biography :

Gayathri Viswanathan is a PhD graduate under the supervision of Dr. Ildiko Szabo, Biochemistry and Biophysics Laboratory, University of Padova, Department of Biology, Italy. Her research interests are stem cell, regenerative medicine, cancer and oncology, Therapeutic potential of Azadiradione on Lung cancer and Selective elimination of breast cancer cells via modulation of potassium channels.