Ion-Channel-Targeting Scorpion Recombinant Toxin as Novel Therapeutic Agent for Breast Cancer

Abstract

Breast cancer remains the leading cause of cancer-related mortality among women worldwide, with limited therapeutic efficacy due to treatment resistance and adverse effects. Emerging evidence suggests that ion channels play crucial roles in tumor progression, regulating proliferation, apoptosis, migration, and metastasis. Voltage-gated potassium (Kv) and sodium (Nav) channels have been implicated in oncogenic signaling pathways. Scorpion venom peptides, known for their selective ion-channel-blocking properties, have demonstrated promising antineoplastic activity. This study explores the potential therapeutic applications of bioactive fractions derived from Chihuahuanus coahuilae, in breast cancer cell lines. Through chromatographic separation, mass spectrometry, and functional assays, we assess their effects on cell viability, proliferation, and ion channel modulation. Our preliminary data suggest that these venom-derived peptides interfere with cancer cell homeostasis by altering ion fluxes, promoting apoptosis, and inhibiting metastatic traits. These findings support the therapeutic potential of ion-channel-targeting peptides as selective anticancer agents. Further investigations into their molecular mechanisms may pave the way for novel, targeted therapies with improved efficacy and specificity for breast cancer treatment.

Keywords: C. coahuliae; antineoplastic; breast cancer; cell viability; doxorubicin; ion channel; proliferation.

Figure 1

Identification of Fas (CD95) expression by flow cytometry in the MCF-7 cell line using an antiCD95 antibody and FasL-biotin reagent; isotype IgG and streptavidin-PE alone were used as controls. For each experiment 50,000 events were acquired in a Attune NXT flow cytometer, and data were analyzed in FlowJo.

Figure 2

Assessment of viable cells using 7AAD staining by flow cytometry. Dose–response curve illustrating the effect of doxorubicin exposure for 48 h on MCF-7 breast cancer cells. The analysis was conducted using serial dilutions ranging from 12.5 µM to 0.024 µM. Data were acquired via flow cytometry (Attune NxT) to evaluate the impact of doxorubicin on cell viability.

Figure 3

Antagonistic interaction of doxorubicin and recombinant toxin rChcoh43 in MCF-7 breast cancer cells. (A) Dose–response curve using doxorubicin at a fixed concentration of 0.1 µM and serial dilutions of rChcoh43 starting at 0.575 µM. (B) Comparative analysis of doxorubicin (0.1 µM), rChcoh43 (0.008 µM), and native nChcoh43 toxin, alongside doxorubicin alone, using untreated cells as controls in standard medium. Cell viability was assessed after 48 h of incubation. Data were assessed through an Attune NxT flow cytometer. Experiments were performed in triplicate. Statistical analysis was conducted as described in the Materials and Methods section.

Figure 4

Evaluation of Ki-67 expression in MCF-7 cells by flow cytometry. Cells were incubated for 48 h with native (n) (0.743 µM) and recombinant (r) Chcoh43 (1.437 µM) toxin. Data were acquired by an Attune NxT flow cytometer. Experiments were performed in triplicate. Statistical analysis was conducted as described in the Materials and Methods section.