title: Effects of the Bowman-Birk inhibitor on clonogenic survival and cisplatin- or radiation-induced cytotoxicity in human breast, cervical, and head and neck cancer cells.
abstract: Bowman-Birk inhibitor (BBI) is a soybean-derived anticarcinogenic protease inhibitor previously shown to potentiate cisplatin-induced cytoxicity in human lung and ovarian cancer cells. To further assess the potential of BBI as a sensitizing agent for cancer radiotherapy and chemotherapy, we evaluated the effects of BBI and a soybean concentrate enriched in BBI known as BBI concentrate (BBIC) on clonogenic survival and radiation- or cisplatin-induced cell killing in MCF7 human breast carcinoma cells, SCC61 and SQ20B human head and neck carcinoma cells, HeLa, HeLa-R1, and HeLa-R3 human cervical carcinoma cells, MCF10 nontumorigenic human epithelial cells, HTori-3 nontumorigenic human thyroid epithelial cells, and C3H10T1/2 mouse fibroblast cells. BBI and BBIC significantly suppressed the clonogenic survival of MCF7 and SCC61 cells. BBIC also suppressed the survival of SQ20B cells and enhanced radiation-induced cell killing in SCC61 and SQ20B cells and cisplatin-induced cell killing in HeLa, HeLa-R1, and HeLa-R3 cells. In contrast, BBI and/or BBIC did not enhance radiation-induced cell killing in MCF10 cells or cisplatin-induced cell killing in C3H10T1/2 cells. BBI did not significantly affect the survival of SQ20B cells or enhance radiation-induced cell killing in SCC61 and SQ20B cells. The clonogenic survivals of MCF10 and C3H10T1/2 cells were not adversely affected by treatment with BBI or BBIC. The clonogenic survival of HTori-3 cells was only moderately suppressed by treatment with BBIC at > or = 80 micrograms/ml. These results suggest that BBIC could be a useful agent for the potentiation of radiation- and cisplatin-mediated cancer treatment without significant adverse effects on surrounding normal tissues.
authors.affiliation: Department of Radiation Oncology, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: X S
authors.initials: XS
authors.lastname: Wan
authors.forename: J J
authors.initials: JJ
authors.lastname: Donahue
authors.forename: J H
authors.initials: JH
authors.lastname: Ware
authors.forename: A R
authors.initials: AR
authors.lastname: Kennedy
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology; D000704:Analysis of Variance; D001943:Breast Neoplasms / Q000473:pathology*; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002945:Cisplatin; D004305:Dose-Response Relationship, Drug; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D011827:Radiation; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000494:pharmacology*; D014361:Trypsin Inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014410:Tumor Stem Cell Assay; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors; D002945:Cisplatin