Comparative efficacy of fractionated Cape cobra (Naja nivea) venom on breast and cervical cancer cells

Introduction: Cancer remains a leading global cause of mortality, with an estimated 20 million new cases and 9.7 million deaths reported in 2022, projected to rise to 35 million by 2050 . In South Africa, it accounts for nearly a quarter of premature non-communicable disease deaths. Chemotherapy remains the most widely used treatment, but its lack of specificity and associated side effects highlight the urgent need for targeted therapies. Venoms have gained attention as potential drug sources, with some venom-derived compounds already FDA-approved for conditions such as hypertension. Snake venoms contain bioactive components with selective cytotoxicity against cancer cells. However, little is known about South African snake venoms, and the anti-cancer potential of fractionated Cape cobra (Naja nivea) venom has not been systematically explored. This study represents a novel investigation into its efficacy against breast and cervical cancer cell lines. Methods: Composition of the Cape cobra venom fractions was previously identified using high-resolution liquid chromatography-mass spectrometry (HR-LC-MS/MS). Six fractions were initially screened for cytotoxic effects, and the two most potent were selected for further testing. These were evaluated on breast (MCF7, T47D, MDA-MB-231) and cervical (CaSki, SiHa, HeLa) cancer cell lines, alongside non-malignant fibroblast (FG0) and retinal pigment epithelial (ARPE-19) cells. Short-term cytotoxicity was assessed by MTT assay and IC50 values calculated. Based on these results, long-term assays were conducted, including clonogenic assays to assess colony-forming ability and scratch assays to assess cell migration. Stability of venom fractions was evaluated using high-performance liquid chromatography (HPLC). Results: Fractions 5 and 6 showed the greatest cytotoxicity, significantly reducing viability in breast (MCF7, T47D) and cervical (CaSki, SiHa) cancer cell lines. In contrast, their effects on non-malignant FG0 and ARPE-19 cells were minimal, with survival rates above 70%. Dose-dependent decreases in colony formation were observed in MCF7 and CaSki cells treated with 12 IC50, IC50, and 2X IC50 concentrations. Migration assays revealed reduced motility at these concentrations in only the SiHa cell line. HPLC analysis showed that repeated freeze-thaw cycles, up to 3 times, resulted in degradation of the venom fractions. Furthermore, storage of the fractions in PBS led to degradation in a manner proportional to the duration of storage. In contrast, the lyophilised venom fractions remained stable over the same period. Conclusion: Cape cobra venom fractions exhibit anti-cancer activity, particularly against ER+ breast and HPV-16 cervical cancer cell lines. Fractions 5 and 6 showed strong activity in MCF7 and slightly less activity in CaSki cell lines , with minimal impact on non-malignant cells, indicating potential selectivity. The stability data highlight challenges in handling and storage but do not diminish their therapeutic promise. Collectively, these findings suggest that Cape cobra venom components represent promising candidates for further development as selective breast and cervical cancer therapies.

Grantor dc:publisher

Stellenbosch : Stellenbosch University

Year dc:date.issued

2026

Author dc:creator

• Palekar, Sidrah

Advisors dc:contributor.advisor

• Kellermann, Tracy A.
• Prince, Sharon
• Khan, Saif F.

Language dc:language.iso

en

Repository record dc:identifier.uri

https://scholar.sun.ac.za/handle/10019.1/135965

OAI identifier oai:identifier

oai:scholar.sun.ac.za:10019.1/135965