BMP7 mediates the anticancer effect of honokiol by upregulating p53 in HCT116 cells
BMP7 mediates the anticancer effect of honokiol by upregulating p53 in HCT116 cells
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BMP7通过上调HCT116细胞中的p53介导和厚朴酚的抗癌作用
DOI：
10.3892/ijo.2017.4078
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发表时间：
2017-09-01
影响因子：
5.2
通讯作者：
Sun, Wen-Juan
中科院分区：
文献类型：
--
作者：
Liu, Rong-Xing;Ren, Wen-Yan;Sun, Wen-Juan
结直肠癌（CRC）是癌症死亡的第二大原因。因此，迫切需要探索治疗结直肠癌的新型有效药物。厚朴酚（HNK）是一种从厚朴树皮中提取的天然产物，具有多种生物活性，包括抗癌。本研究采用细胞活力测定、western blotting、real-time PCR和免疫荧光染色等方法，探讨了HNK的抗癌作用及其可能的生物学机制。我们发现HNK能够抑制HCT116细胞的增殖和诱导细胞凋亡，并呈浓度依赖性和时间依赖性。HNK激活HCT116和其他结肠癌细胞中的p53。外源性p53增强了HNK的抗癌作用，而p53抑制剂降低了HNK的抗癌作用。此外，HNK上调结肠癌细胞中骨形态发生蛋白7 （bone morphogenetic protein 7, BMP7）的表达；外源性BMP7增强了HNK的抗癌活性，BMP7特异性抗体降低了HNK的抗癌作用。机制方面，我们发现HNK不能提高Smad1/5/8的水平；外源性BMP7增强了hnk诱导的p53激活。相反，BMP7特异性抗体抑制hnk诱导的结肠癌细胞中p53的活化，并部分降低p53的总水平。我们的研究结果表明，HNK可能是一种很有前景的CRC抗癌药物；p53的激活在HNK的抗癌活性中起着重要作用，HNK的抗癌活性可能部分是由HNK诱导的BMP7的上调初始化的。
Colorectal cancer (CRC) is the second leading cause of cancer death. Hence, there is a great need to explore new efficacious drugs for the treatment of CRC. Honokiol (HNK), a natural product extracted from magnolia bark, processes various biological activities, including anticancer. In this study, we introduced cell viability assay, western blotting, real-time PCR and immunofluorescent staining to determine the anticancer effect of HNK, and the possible mechanism underlying this biological process. We found that HNK can inhibit the proliferation and induce apoptosis in HCT116 cells in a concentration- and time-dependent manner. HNK activates p53 in HCT116 and other colon cancer cells. Exogenous p53 potentiates the anticancer of HNK, while p53 inhibitor decreases this effect of HNK. Moreover, HNK upregulates the expression of bone morphogenetic protein 7 (BMP7) in colon cancer cells; Exogenous BMP7 enhances the anticancer activity of HNK and BMP7 specific antibody reduces this effect of HNK. For mechanism, we found that HNK cannot increase the level of Smad1/5/8; Exogenous BMP7 potentiates the HNK-induced activation of p53. On the contrary, BMP7 specific antibody inhibits the HNK-induced activation of p53 in colon cancer cells and partly decreases the total level of p53. Our findings suggested that HNK may be a promising anticancer drug for CRC; activation of p53 plays an important role in the anticancer activity of HNK, which may be initialized partly by the HNK-induced upregulation of BMP7.