title: Identification and structural characterization of a new pro-apoptotic cyclic octapeptide cyclosaplin from somatic seedlings of Santalum album L.
abstract: Small cyclic peptides exhibiting potent biological activity have great potential for anticancer therapy. An antiproliferative cyclic octapeptide, cyclosaplin was purified from somatic seedlings of Santalum album L. (sandalwood) using gel filtration and RP-HPLC separation process. The molecular mass of purified peptide was found to be 858 Da and the sequence was determined by MALDI-ToF-PSD-MS as 'RLGDGCTR' (cyclic). The cytotoxic activity of the peptide was tested against human breast cancer (MDA-MB-231) cell line in a dose and time-dependent manner. The purified peptide exhibited significant antiproliferative activity with an IC50 2.06 μg/mL. In a mechanistic approach, apoptosis was observed in differential microscopic studies for peptide treated MDA-MB-231 cells, which was further confirmed by mitochondrial membrane potential, DNA fragmentation assay, cell cycle analysis and caspase 3 activities. The modeling and docking experiments revealed strong affinity (kcal/mol) of peptide toward EGFR and procaspase 3. The co-localization studies revealed that the peptide sensitizes MDA-MB-231 cells by possibly binding to EGFR and induces apoptosis. This unique cyclic octapeptide revealed to be a favorable candidate for development of anticancer agents.
authors: Plant Biotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
authors: Abheepsa
authors: A
authors: Mishra
authors: Plant Biotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
authors: Samiran S
authors: SS
authors: Gauri
authors: Plant Biotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
authors: Sourav K
authors: SK
authors: Mukhopadhyay
authors: Plant Biotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
authors: Soumya
authors: S
authors: Chatterjee
authors: Plant Biotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
authors: Shibendu S
authors: SS
authors: Das
authors: Central Research Facility, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India.
authors: Santi M
authors: SM
authors: Mandal
authors: Plant Biotechnology Laboratory, Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, West Bengal, India. Electronic address: satyahari01@yahoo.com.
authors: Satyahari
authors: S
authors: Dey
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D020128:Inhibitory Concentration 50; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D062105:Molecular Docking Simulation; D010456:Peptides, Cyclic / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D032123:Santalum / Q000737:chemistry*; D036226:Seedlings / Q000737:chemistry
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010456:Peptides, Cyclic; C000597543:cyclo(arginyl-leucyl-glycyl-aspartyl-glycyl-cysteinyl-threonyl-arginyl); C512478:EGFR protein, human; D066246:ErbB Receptors; D053148:Caspase 3
keywords: Antiproliferative; Apoptosis; Caspase 3; Cyclic peptide; Cyclosaplin; Sandalwood