Luteolin overcomes resistance to benzyl isothiocyanate-induced apoptosis in human colorectal cancer HCT-116 cells
Luteolin overcomes resistance to benzyl isothiocyanate-induced apoptosis in human colorectal cancer HCT-116 cells
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DOI：
10.38212/2224-6614.2122
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发表时间：
2020-07
影响因子：
3.6
通讯作者：
R. Sakai;Shintaro Yokobe;Naomi Abe;N. Miyoshi;Y. Murata;Yoshimasa Nakamura
中科院分区：
文献类型：
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作者：
R. Sakai;Shintaro Yokobe;Naomi Abe;N. Miyoshi;Y. Murata;Yoshimasa Nakamura
我们之前已经鉴定出 p53（一种基因毒性应激的通用传感器）是正常结肠成纤维细胞中异硫氰酸苄酯 (BITC) 诱导细胞凋亡的负调节因子。在本研究中，我们进一步证实，与野生型p53的HCT-116细胞相比，BITC有可能在p53突变的结肠癌HT-29细胞中诱导细胞毒性。为了有效诱导 BITC 刺激的 p53 阳性细胞凋亡，我们研究了 BITC 与可能克服 BITC 耐药性的食品成分的联合作用。用木犀草素预处理可增强 BITC 在 HCT-116 细胞中诱导的细胞毒性，但在 HT-29 细胞中则不然。木犀草素还增强了与细胞凋亡相关的生化事件，例如 DNA 梯的形成和 caspase-3 的激活。木犀草素减弱 p21^waf1/cip1 的表达，p21^waf1/cip1 是 p53 的关键下游靶标。这些结果表明 p21^waf1/cip1 途径在木犀草素克服 BITC 耐药性中的作用。
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 p21^waf1/cip1, a key downstream target of p53. These results suggest the role of p21^waf1/cip1 pathway in the overcoming BITC resistance by luteolin.