Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway.
Anticancer effect of involucrasin A on colorectal cancer cells by modulating the Akt/MDM2/p53 pathway.
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DOI：
10.3892/ol.2023.13804
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发表时间：
2023-06
期刊：
影响因子：
2.9
通讯作者：
Ma W
中科院分区：
文献类型：
--
作者：
Wei C;Du J;Shen Y;Wang Z;Lin Q;Chen J;Zhang F;Lin W;Wang Z;Yang Z;Ma W
结直肠癌(CRC)是全球第二大癌症死亡原因，但临床上仍缺乏有效的抗结直肠癌药物。天然化合物被认为是新的抗肿瘤药物的潜在有价值的来源。天花粉蛋白A是从天山苍耳中分离得到的一种新的天然分子。鬼魂由我们的团队提供。本研究以HCT-116结直肠癌细胞为实验对象，研究了白藜芦素A的抗癌活性。首先，采用硫代罗丹明B法和集落形成实验分析了雪兰素A对HCT-116细胞的增殖抑制作用。结果表明，白蜡梅素A对体外培养的HCT-116结直肠癌细胞有明显的抑制作用。随后，流式细胞仪和Western blotting结果显示，白藜芦素A以剂量依赖的方式诱导细胞凋亡，并上调Caspase6和Caspase9等凋亡相关蛋白的表达水平。机制上，白藜芦素A显著抑制Akt和小鼠双分钟2同系物(MDM2)的磷酸化，导致细胞内P53水平升高。这是逆转的外源表达的构成活性形式的Akt。类似地，无论是敲除P53还是敲除Bax，都能阻断白藜芦素A诱导的增殖抑制和细胞凋亡。综上所述，本研究表明，白蜡梅素A通过调控Akt/MDM2/P53通路发挥抗肿瘤作用，值得在临床前和临床试验中进一步探索。
Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide; however, there is still a lack of effective clinical anti-CRC agents. Naturally-occurring compounds have been considered a potentially valuable source of new antitumorigenic agents. Involucrasin A, a novel natural molecule, was isolated from Shuteria involucrata (Wall.) Wight & Arn by our team. In the present study, the anticancer activity of involucrasin A in HCT-116 CRC cells was evaluated. Firstly, the anti-proliferative effect of involucrasin A on HCT-116 cells was analyzed by sulforhodamine B and colony formation assays. The results revealed that involucrasin A exhibited a potent inhibitory effect on HCT-116 CRC cell proliferation in vitro. Subsequently, flow cytometry and western blotting indicated that involucrasin A induced apoptosis and upregulated the expression levels of apoptosis-related proteins, such as cleaved-caspase 6 and cleaved-caspase 9, in a dose-dependent manner. Mechanistically, involucrasin A significantly inhibited the phosphorylation of Akt and murine double minute 2 homologue (MDM2), which resulted in increased intracellular levels of p53. This was reversed by exogenous expression of the constitutively active form of Akt. Similarly, either knocking out p53 or knocking down Bax abrogated involucrasin A-induced proliferation inhibition and apoptosis. Together, the present study indicated that involucrasin A exerts antitumorigenic activities via modulating the Akt/MDM2/p53 pathway in HCT-116 CRC cells, and it is worthy of further exploration in preclinical and clinical trials.
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影响因子：
56.9
作者：
Bunz, F;Dutriaux, A;Vogelstein, B
通讯作者：
Vogelstein, B
影响因子：
37.3
作者：
Park MH;Hong JE;Park ES;Yoon HS;Seo DW;Hyun BK;Han SB;Ham YW;Hwang BY;Hong JT
通讯作者：
Hong JT
影响因子：
9
作者：
Ni T;He Z;Dai Y;Yao J;Guo Q;Wei L
通讯作者：
Wei L
影响因子：
10.5
作者：
Chen, WS;Xu, PZ;Hay, N
通讯作者：
Hay, N
影响因子：
64.8
作者：
Evan, GI;Vousden, KH
通讯作者：
Vousden, KH