Discovery of Leptulipin, a New Anticancer Protein from theIranian Scorpion, Hemiscorpius lepturus

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.

Molecular Characterization and In Silico Analyses of Maurolipin Structure as a Secretory Phospholipase A 2 (

“…The detected PLA 2 has encoded a protein of 144 amino acid residue named Maurolipin. Till now, several studies reported the genes encoding phospholipases A 2 from different species of scorpions, including Hemilipin from H. lepturus [ 23 ], Leptulipin from H. lepturus [ 25 ], Imperatoxin I and Phospholipin from P. imperator [ 21 , 22 ], Phaiodactylipin from A. phaiodactylus [ 20 ], Heteromtoxin from Heterometrus laoticus [ 10 ], Phospholipase A 2 from H. fulvipes [ 46 ], MtPL A 2 from Mesobuthus tumulus [ 47 ], Sm-PLVG from Tunisian S. maurus [ 27 ], and Phospholipase A 2 from Hadrurus gertschi [ 48 ].…”

“…sPLA 2 from the venom glands of scorpions is classified as a group III subfamily [20]. sPLA 2 has been identified from different species of scorpions till now, including Pandinus imperator [21,22], Hemiscorpius lepturus [23][24][25], Anuroctonus phaiodactylus [20], Heterometrus fulvipes [26], Heterometrus laoticus [10], and Tunisian Scorpio maurus [27].…”

Scorpion Venom as a Source of Antimicrobial Peptides: Overview of Biomolecule Separation, Analysis and Characterization Methods

“…The final isolated fraction with distinctive cytotoxic activity was then identified by 2-DGE. The bioactivities of Hemiscorpius lepturus peptides discovered in specific fractions constitute novel biomolecules with potential pharmacological use [ 84 ]. Different neurotoxins in scorpion venom are accountable for the various envenomation effects in humans, especially cardiotoxic peptides that cause severe cardiorespiratory complications to envenomation victims [ 85 ].…”