Identification and structural characterization of a new pro-apoptotic cyclic octapeptide cyclosaplin from somatic seedlings of Santalum album L

• Published in: Peptides (New York, N.Y. : 1980) Vol. 54; pp. 148 - 158
• Main Authors: Mishra, Abheepsa, Gauri, Samiran S., Mukhopadhyay, Sourav K., Chatterjee, Soumya, Das, Shibendu S., Mandal, Santi M., Dey, Satyahari
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2014
• Subjects: Anticancer properties; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Antiproliferative; Antiproliferatives; Apoptosis; Apoptosis - drug effects; Binding; Biological; Breast; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Caspase 3; Caspase 3 - metabolism; Cell Line, Tumor; Cyclic peptide; Cyclosaplin; DNA Fragmentation - drug effects; Dose-Response Relationship, Drug; Female; Humans; Inhibitory Concentration 50; Membrane Potential, Mitochondrial - drug effects; Molecular Docking Simulation; Peptides; Peptides, Cyclic - chemistry; Peptides, Cyclic - isolation & purification; Peptides, Cyclic - pharmacology; Receptor, Epidermal Growth Factor - metabolism; Sandalwood; Santalum - chemistry; Seedlings - chemistry; Therapy; PBS; Antiproliferative; Sandalwood; DTT; UV-DAD; DAPI; MTT; TFA; EGFR; RP-HPLC; Cyclic peptide; Calcein AM; NH4HCO3; Caspase 3; PI; CHCA; TNBC; Cyclosaplin; Rh 123; EthD-1; MALDI-ToF-PSD-MS; Apoptosis
• DOI: 10.1016/j.peptides.2014.01.023
• ISSN: 0196-9781

•A cyclic octapeptide was characterized from somatic seedlings of sandalwood.•The peptide was sequenced as ‘RLGDGCTR’, named ‘cyclosaplin’.•Cyclosaplin showed anti-proliferative activity against MDA-MB-231 cell line cancer cells.•Induces caspase 3 mediated apoptosis. 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 858Da 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 2.06μg/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.