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Table 1. Cytotoxicity (IC 50 ) a of selected cyclic decapeptides against a panel of humancarcinoma cells and non-malignant fibroblasts (N1), and hemolytic activityCode MDA-MB-231 HeLa HepG2 A431 Panc-1 Hemolysis b N1BPC88 31.2 22.5 32.5 28.0 32.5 33 42.0BPC94 22.0 23.0 20.5 21.5 18.5 73 nd cBPC96 40.0 24.5 34.5 35.0 51.0 32 39.0BPC98 40.7 38.5 44.0 47.5 44.5 36 58.5BPC184 32.2 30.5 42.2 24.5 41.5 89 ndBPC194 32.5 29.5 46.0 50.0 40.0 17 56.5BPC198 53.2 35.0 >60 49.5 57.5 14 7.5BPC202 40.5 54.0 46.0 35.5 43.5 2 nda Cells were treated for 48 h. Cytotoxicity ( M) was determined using the MTT assayb Percentage of erythrocytes hemolysis at 375 Mc Not determinedPeptide BPC96 was selected to study its ability to synergize with cisplatin in HeLa cells.These cells were co-treated for 48 h with different concentrations of BPC96 (5-30 M)along with a fixed cisplatin dose (1.5, 2.5, 4.5, and 6.5 M). A strong synergisticcytotoxicity in all cisplatin concentrations assayed was observed. Interestingly, thissynergistic effect was even significant when the lowest BPC96 concentration tested (5 M)was combined with the lowest cisplatin dose assayed (1.5 M). The lethality of HeLa cellstreated with 5 M BPC96 or with 1.5 M cisplatin was 8% and 5%, respectively, whilelethality of HeLa cells co-treated with 1.5 M cisplatin plus 5 M BPC96 increased to25%. Analysis by the isobole method showed a median interaction index value of 0.74,indicating a marked synergistic interaction.AcknowledgmentsFinancial support was provided by grant from the University of Girona (Grant for R+D Projects onHealth Sciences). We are also grateful to the Serveis Tècnics de Recerca of the University of Gironafor their support with the mass spectrometry analysis. We acknowledge the Banc de Sang i Teixits ofJosep Trueta Hospital of Girona for supplying us the human serum and to Girona Division of CatalanInstitute of Oncology Hospital Pharmacy for providing us the cisplatin.References1. Hoskin, D.W., Ramamoorthy, A. Biochim. Biophys. Acta 1778, 357-357 (2008).2. Leuschner, C., Hansel, W. Curr. Pharm. Design 10, 2299-2310 (2004).3. Mader, J.S., Hoskin, D.W. Expert Opin. Investig. Drugs 15, 933-946 (2006).4. Monroc, S., Badosa, E., Besalú, E., Planas, M., Bardají, E., Montesinos, E., Feliu, L. Peptides 27,2575-2584 (2006).301