RETRACTED: Adenine Combined with Cisplatin Promotes Anticancer Activity against Hepatocellular Cancer Cells through AMPK-Mediated p53/p21 and p38 MAPK Cascades (Retracted Article)

被引:8
作者
Huang, Jhen-Yu [1 ]
Lin, You-Cian [2 ,3 ]
Chen, Han-Min [4 ]
Lin, Jiun-Tsai [5 ]
Kao, Shao-Hsuan [1 ,6 ]
机构
[1] Chung Shan Med Univ, Coll Med, Inst Med, Taichung 402306, Taiwan
[2] China Med Univ Hosp, Surg Dept, Cardiovasc Div, Taichung 404332, Taiwan
[3] China Med Univ, Coll Med, Sch Med, Taichung 404332, Taiwan
[4] Catholic Fu Jen Univ, Inst Appl Sci & Engn, New Taipei 242048, Taiwan
[5] Energenesis Biomed Co Ltd, Taipei 114694, Taiwan
[6] Chung Shan Med Univ Hosp, Dept Med Res, Taichung 402306, Taiwan
关键词
adenine; cisplatin; hepatocellular carcinoma cells; AMP-activated protein kinase; apoptosis; PROTEIN-KINASE CONTRIBUTES; MOLECULAR-MECHANISMS; SIGNALING PATHWAY; CYCLE ARREST; HEPG2; CELLS; IN-VITRO; S-PHASE; CARCINOMA; APOPTOSIS; GROWTH;
D O I
10.3390/ph15070795
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Cisplatin has been widely used in cancer treatments. Recent evidence indicates that adenine has potential anticancer activities against various types of cancers. However, the effects of the combination of adenine and cisplatin on hepatocellular carcinoma (HCC) cells remain sketchy. Here, our objective was to elucidate the anticancer activity of adenine in combination with cisplatin in HCC cells and its mechanistic pathways. Cell viability and cell cycle progression were assessed by the SRB assay and flow cytometry, respectively. Apoptosis was demonstrated by PI/annexin V staining and flow cytometric analysis. Protein expression, signaling cascade, and mRNA expression were analyzed by Western blotting and quantitative RT-PCR, respectively. Our results showed that adenine jointly potentiated the inhibitory effects of cisplatin on the cell viability of SK-Hep1 and Huh? cells. Further investigation showed that adenine combined with cisplatin induced higher S phase arrest and apoptosis in HCC cells. Mechanically, adenine induced AMPK activation, reduced mTOR phosphorylation, and increased p53 and p21 levels. The combination of adenine and cisplatin synergistically reduced Bcl-2 and increased PUMA, cleaved caspase-3, and PARP in HCC cells. Adenine also upregulated the mRNA expression of p53, p21, PUMA, and PARP, while knockdown of AMPK reduced the increased expression of these genes. Furthermore, adenine also induced the activation of p38 MAPK through AMPK signaling, and the inhibition of p38 MAPK reduced the apoptosis of HCC cells with exposure to adenine combined with cisplatin. Collectively, these findings reveal that the combination of adenine and cisplatin synergistically enhances apoptosis of HCC cells, which may be attributed to the AMPK-mediated p53/p21 and p38 MAPK cascades. It suggests that adenine may be a potential adjuvant for the treatment of HCC in combination with cisplatin.
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页数:14
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