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.

Can We Improve the Nutritional Quality of Legume Seeds?

“…These may confer an indirect benefit to humans by protecting pods from pests. Recent research on the homologous TI proteins from soybean suggests a direct nutritional role in the prevention of certain proteolytic and related processes in tumorigenic cells (Zhang et al, 1999).…”

Crystal structure of the anticarcinogenic Bowman–Birk inhibitor from snail medic (Medicago scutellata) seeds complexed with bovine trypsin

“…The resolution achieved in some of these structures was moderate as well as the level of completeness of the data in the highest resolution shells. The discovery that Bowman-Birk inhibitors have anticarcinogenic eVects on many diVerent cell lines (Yavelow et al, 1985;Billings and Habres, 1992;Zhang et al, 1999;Miyata et al, 2000;Meyskens, 2001;Kennedy and Wan, 2002;Kennedy, 1998a,b) and radioprotective eVects on normal tissue (Dittmann et al, 2003;Dittmann et al, 2000) arouse considerable interest as these molecules begun to be viewed as potential new useful agents in cancer therapy. Much eVort is currently being devoted to the study of the possible mechanisms of these actions that are thought, at least in some cases, to be linked to the protease inhibition activity of these molecules (Billings et al, 1988;Ware et al, 1997Ware et al, , 1999.…”

Legume-Derived Bioactive Compounds for the Prevention and Treatment of Breast Cancer

“…Moreover, variations in the dose and time of exposure are also important factors to be considered. For example, low Bowman-Birk PIs concentrations (10-40 µM) and long incubation periods (6-14 days) are frequently associated with proliferation inhibition (Wan et al, 1998;Zhang et al, 1999); while high concentration (200 µM) and short incubation periods (3 days) has been described to induce both tumor growth inhibition and cell death (Joanitti et al, 2010). Overall, these findings indicate that PIs are promising anticancer molecules and encourage more studies of these compounds on breast cancer.…”

“…A Bowman-Birk PI isolated from Hokkaido large black soybeans seeds and a Kunitz PI isolated from Chinese black soybean seeds have been described to suppress the proliferation of breast cancer cells (MCF-7) in vitro (Ho et al, 2008;Ye et al, 2009). Similar effects were observed in MCF-7 cells treated with Bowman-Birk PIs derived from soy or black-eyed peas (Zhang et al, 1999;Joanitti et al, 2010). Conversely, it was described that soy BBI was not able to induce anticancer effects on ER-negative breast cancer cell MDA-MB 231 (Hsieh et al, 2010).…”

“…Nevertheless, the precise mechanisms by which PIs exerts their preventive and suppressive anticancer effects are not completely elucidated on breast cancer. One of the main effects observed in tumor cells treated with PIs is a reduction on cell proliferation rates (Wan et al, 1998;Zhang et al, 1999;Chen et al, 2005). In 2005, Chen et al reported a landmark research study revealing some clues about the mechanisms involved in this growth inhibition.…”