Luteolin Overcomes Resistance to Benzyl Isothiocyanate-Induced Apoptosis in Human Colorectal Cancer HCT-116 Cells
RIEKO SAKAI1, SHINTARO YOKOBE1, NAOMI ABE1, NORIYUKI MIYOSHI2, YOSHIYUKI MURATA1 AND YOSHIMASA NAKAMURA1*
1. Graduate School of Natural Science and Technology, Okayama University, Okayama, Japan
2. Laboratory of Biochemistry, Graduate School of Nutritional and Environmental Sciences, and Global COE Program, University of Shizuoka, Shizuoka, Japan
ABSTRACT
We have previously identified p53, a universal sensor of genotoxic stress, as a negative regulator of the apoptosis induction by benzyl isothiocyanate (BITC) in the normal colon fibroblastoid cells. In the present study, we further confirmed that BITC has a potential to induce cytotoxicity in the p53-mutated colon cancer HT-29 cells in preference to HCT-116 cells with wild-type p53. To obtain effective induction of BITC-stimulated apoptosis in p53-positive cells, we investigated the combination effect of BITC and food ingredient that may overcome resistance to BITC. Pretreatment with luteolin potentiated the cytotoxicity induction by BITC in HCT-116 cells but not in HT-29 cells. The biochemical events related to apoptosis such as DNA ladder formation and caspase-3 activation were also enhanced by luteolin. Luteolin attenuated the expression of p21waf1/cip1, a key downstream target of p53. These results suggest the role of p21waf1/cip1 pathway in the overcoming BITC resistance by luteolin.
Key words: benzyl isothiocyanate, luteolin, apoptosis, caspase-3, p21waf1/cip1, HT-29 cells, HCT116 cells