Identification and Structural Characterization of a new Pro-apoptotic Cyclic Octapeptide Cyclosaplin from Somatic Seedlings of Santalum album L

Publication date: Available online 3 February 2014 Source:Peptides

Author(s): Abheepsa Mishra , Samiran S. Gauri , Sourav K. Mukhopadhyay , Soumya Chatterjee , Shibendu S. Das , Santi M. Mandal , Satyahari Dey

Small cyclic peptides exhibiting potent biological activity have great potential for anticancer therapy. An antiproliferative cyclic octapeptide 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 towards 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 developing of anticancer agents.

Graphical abstract