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 ≥80 mg/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.