The phytochemical p-hydroxycinnamic acid suppresses the growth and stimulates the death in human liver cancer HepG2 cells.
The phytochemical p-hydroxycinnamic acid suppresses the growth and stimulates the death in human liver cancer HepG2 cells.
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DOI：
10.1097/cad.0000000000001059
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发表时间：
2021-06-01
影响因子：
2.3
通讯作者：
Ramos JW
中科院分区：
文献类型：
--
作者：
Yamaguchi M;Murata T;Ramos JW
肝细胞癌是最常见的恶性疾病之一，占癌症相关死亡的三分之一。尽管发展了新的治疗策略，但晚期肝癌的预后和有效治疗仍然很差。在本研究中，我们研究了植物分子对羟基肉桂酸(HCA)在体外对HepG2肝癌模型中的抗癌作用。HCA(10-1000 nM)培养可抑制HepG2细胞集落形成和生长。从机制上讲，在HCA的作用下，RAS、PI3K、Akt、MAPK、NF-κB p65和β-catenin的水平降低，而视网膜母细胞瘤和Regucalin的水平增加，而Ras、PI3K、Akt、MAPK、NF-Bp65和Rg-catenin与细胞信号和转录过程有关，而Rb则是癌变的抑制因子。这些改变可能导致细胞生长受抑。此外，用HCA(10-1000 nM)培养时，由于caspase-3水平升高而刺激细胞死亡。有趣的是，HCA对HepG2细胞生长和死亡的影响被芳香烃受体(AHR)拮抗剂CH223191所抑制，这表明类黄酮的作用至少部分是通过激活AHR信号来实现的。值得注意的是，HCA阻断了L钙通道激动剂Bay K8644对HepG2细胞生长的刺激作用。因此，我们的研究表明，HCA在体外对人肝癌细胞HepG2具有抑制生长和刺激死亡的作用。因此，植物学分子HCA可能成为治疗肝癌的有用工具，为人类肝癌的治疗提供了一种新的策略。
Hepatocellular carcinoma (HCC) is one of the most prevalent malignant diseases and causes a third of cancer-related death. The prognosis and effective treatment of advanced HCC remains poor in spite of the development of novel therapeutic strategies. In the present study, we investigate anticancer effects of the botanical molecule p-hydroxycinnamic acid (HCA) in the HepG2 liver cancer model in vitro. Culturing with HCA (10–1000 nM) suppressed colony formation and growth of HepG2 cells. Mechanistically, culturing with HCA decreased levels of Ras, PI3K, Akt, MAPK, NF-κB p65 and β-catenin, which are linked to processes of cell signaling and transcription, and increased levels of retinoblastoma and regucalcin, which are suppressors for carcinogenesis. These alterations may lead to the suppression of cell growth. Furthermore, culturing with HCA (10–1000 nM) stimulated cell death due to increased caspase-3 levels. Interestingly, the effects of HCA on the growth and death of HepG2 cells were inhibited by culturing with CH223191, an antagonist of aryl hydrocarbon receptor (AHR), suggesting that the flavonoid effects are, at least partly, mediated by activation of AHR signaling. Notably, HCA blocked stimulatory effects of Bay K 8644, an agonist of L-type calcium channel, on the growth of HepG2 cells. Thus, our study demonstrates that HCA suppresses the growth and stimulates the death of human liver cancer HepG2 cells in vitro. The botanical molecule HCA may therefore be a useful tool in the treatment of HCC, providing a novel strategy for the therapy of human liver cancers.