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Discovery of Leptulipin, a New Anticancer Protein from theIranian Scorpion, Hemiscorpius lepturus
Ali Rezaei1,2, Saeme Asgari3, Samira Komijani2
1Department of Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 3514799422, Iran.
Abstract:
Cancer is one of the leading causes of mortality in the world. Unfortunately, the present anticancer chemotherapeutics display high cytotoxicity. Accordingly, the discovery of new anticancer agents with lower side effects is highly necessitated. This study aimed to discover an anticancer compound from Hemiscorpius lepturus scorpion venom. Bioactivity-guided chromatography was performed to isolate an active compound against colon and breast cancer cell lines. 2D electrophoresis and MALDI-TOF were performed to identify the molecule. A partial protein sequence was obtained by mass spectrometry, while the full-length was deciphered using a cDNA library of the venom gland by bioinformatics analyses and was designated as leptulipin. The gene was cloned in pET-26b, expressed, and purified. The anticancer effect and mechanism action of leptulipin were evaluated by MTT, apoptosis, and cell cycle assays, as well as by gene expression analysis of apoptosis-related genes. The treated cells displayed inhibition of cell proliferation, altered morphology, DNA fragmentation, and cell cycle arrest. Furthermore, the treated cells showed a decrease in BCL-2 expression and an increase in Bax and Caspase 9 genes. In this study, we discovered a new anticancer protein from H. lepturus scorpion venom. Leptulipin showed significant anticancer activity against breast and colon cancer cell lines.
Insights
Researchers discovered leptulipin, a novel anticancer protein from *Hemiscorpius lepturus* scorpion venom. This compound effectively inhibits breast and colon cancer cell proliferation with reduced cytotoxicity.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Cancer remains a leading global cause of death.
- Current chemotherapy drugs exhibit significant cytotoxicity.
- Novel anticancer agents with improved safety profiles are urgently needed.
Purpose of the Study:
- To isolate and characterize a novel anticancer compound from *Hemiscorpius lepturus* scorpion venom.
- To evaluate the anticancer activity and mechanism of action of the isolated compound against cancer cell lines.
Main Methods:
- Bioactivity-guided chromatography for compound isolation.
- 2D electrophoresis and MALDI-TOF mass spectrometry for identification.
- Gene cloning, expression, and purification of the identified protein (leptulipin).
- MTT, apoptosis, cell cycle, and gene expression assays to assess anticancer effects.
Main Results:
- Leptulipin was isolated and identified from *H. lepturus* venom.
- Leptulipin demonstrated significant inhibition of proliferation in colon and breast cancer cell lines.
- Leptulipin induced apoptosis, cell cycle arrest, and altered cell morphology.
- Leptulipin modulated the expression of apoptosis-related genes, decreasing BCL-2 and increasing Bax and Caspase 9.
Conclusions:
- A new anticancer protein, leptulipin, was discovered from *H. lepturus* scorpion venom.
- Leptulipin exhibits potent anticancer activity against breast and colon cancer cells.
- Leptulipin represents a promising candidate for the development of novel cancer therapeutics with potentially lower side effects.
