Chromatographic Characterization and Anticancer Activity of Scorpio fuscus Venom in Colorectal Cancer Models

To evaluate the anticancer effects of Israeli black scorpion (Scorpio fuscus) venom (SFV) on human colorectal cancer (CRC) models using integrated in vitro and in vivo approaches, researchers characterized SFV constituents using gel electrophoresis, followed by high-performance liquid chromatography (HPLC) and UV-visible (UV-vis) spectrometry. A paper based on this research was published in Investigational New Drugs ^(1).

The third most prevalent cancer worldwide and the second most lethal form of cancer, the incidences of colon and rectal cancer are expected to increase by 71.5% and 60.0%, respectively, by 2035.^(2,3) While surgical excision is the primary treatment for resectable CRC, while chemotherapy, radiotherapy, and immunotherapy are the standard treatments for unresectable CRC, these therapies possess disadvantages, such as high cytotoxicity and lack of specificity, which can result in secondary complications.⁽⁴⁾ While these therapies can be combined based on the extent and progression of the CRC, more than half of the patients still relapse with multidrug-resistant CRC.⁽⁵⁾ Although there has been significant progress in CRC screening, surgery, and adjuvant treatment, the death rate remains high, which spotlights the critical need for cutting-edge therapies which increase the sensitivity of resistant tumors to chemotherapy.⁽⁶⁾

The peptides that make up scorpion venom include neurotoxins which target ion channels in the nervous system and potassium channel-blocking toxins, such as charybdotoxin, that block potassium channels and alter the excitability of neurons and muscles, as well asmetalloproteases, hyaluronidases, and phospholipases, which contribute to tissue degradation, cell membrane disruption, and the spread of venom throughout the prey’s body.^(7,8) In addition, antimicrobial peptides within scorpion venom have been shown torespond positively against bacteria, fungi, and even cancer cells, which highlights their therapeutic potential.⁽⁹⁾ “This biochemical diversity,” write the authors of the article ⁽¹⁾, “makes scorpion venom a rich source for pharmacological research and drug development.”

For this research, identified peptides were subjected to structural modeling and in silico docking analyses against selected proteins associated with colorectal cancer and apoptosis-related pathways. The cytotoxic effects of SFV were assessed in human CRC cell lines (DLD-1, HT-29, and CaCo-2) and a healthy colon epithelial cell line (CCD-18Co) using Alamar Blue assays after 48-h treatment, and half-maximal inhibitory concentration (IC₅₀) values were determined. SFV treatment resulted in a dose-dependent reduction in cancer cell viability, accompanied by decreased migratory capacity and colony formation ability. Apoptotic responses were further evaluated by flow cytometry and gene expression analyses, indicating modulation of apoptosis-associated genes. For in vivo validation, subcutaneous and orthotopic xenograft colon cancer models were established in mice. SFV administration led to reduced tumor growth compared with control groups. Immunohistochemical analyses revealed altered expression patterns of selected tumor-related markers in SFV-treated tumors. Gene expression profiling demonstrated greater than twofold changes in over 50 genes.⁽¹⁾

“Collectively,” write the authors of the study, “these findings indicate that SFV exerts significant antitumor effects in colorectal cancer models and support its potential as a promising anticancer agent, warranting further mechanistic and translational investigation.” ⁽¹⁾,

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References

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Xia, Z.; Xie, L.; Li, B. et al. Antimicrobial Potential of Scorpion-Venom-Derived Peptides. Molecules 2024, 29 (21), 5080. DOI: 10.3390/molecules29215080