Discovery of Leptulipin, a New Anticancer Protein from theIranian Scorpion, <i>Hemiscorpius lepturus</i>
Ali Rezaei,
Saeme Asgari,
Samira Komijani,
Seyedeh Narjes Sadat,
Jean-Marc Sabatier,
Davood Nasrabadi,
Kamran Pooshang Bagheri,
Delavar Shahbazzadeh,
Mohammad Reza Akbari Eidgahi,
Michel De Waard,
Hasan Mirzahoseini
Affiliations
Ali Rezaei
Department of Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 3514799422, Iran
Saeme Asgari
Department of Biochemistry and Biophysics, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran 5157944533, Iran
Samira Komijani
Venom and Biotherapeutics Molecules Laboratory, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
Seyedeh Narjes Sadat
Venom and Biotherapeutics Molecules Laboratory, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
Jean-Marc Sabatier
Institute of NeuroPhysiopathology (INP), Faculté de Pharmacie, Université D’Aix-Marseille, UMR 7051, 27 Bd Jean Moulin, CEDEX 05, 13385 Marseille, France
Davood Nasrabadi
Department of Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 3514799422, Iran
Kamran Pooshang Bagheri
Venom and Biotherapeutics Molecules Laboratory, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
Delavar Shahbazzadeh
Venom and Biotherapeutics Molecules Laboratory, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
Mohammad Reza Akbari Eidgahi
Department of Biotechnology, Faculty of Medicine, Semnan University of Medical Sciences, Semnan 3514799422, Iran
Michel De Waard
L’Institut du Thorax, INSERM, CNRS, University of Nantes, 44000 Nantes, France
Hasan Mirzahoseini
Venom and Biotherapeutics Molecules Laboratory, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran 1316943551, Iran
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.
