?-Terthienyl induces prostate cancer cell death through inhibiting androgen receptor expression

被引:9
|
作者
Gan, Xia [1 ,2 ]
Huang, Hailing [1 ]
Wen, Jing [1 ]
Liu, Kai [2 ]
Yang, Yuting [1 ]
Li, Xiaoning [3 ]
Fang, Gang [1 ]
Liu, Yonghong [2 ,4 ]
Wang, Xueni [1 ,4 ]
机构
[1] Guangxi Univ Chinese Med, Guangxi Zhuang Yao Med Ctr Engn & Technol, 13 Wuhe Rd, Nanning 530200, Peoples R China
[2] Guangxi Univ Chinese Med, Inst Marine Drugs, 13 Wuhe Rd, Nanning 530200, Peoples R China
[3] Nanning Normal Univ, Sch Foreign Languages, 3 Hexing Rd, Nanning 530299, Peoples R China
[4] Chinese Acad Sci, South China Sea Inst Oceanol, CAS Key Lab Trop Marine Bioresources & Ecol, Guangdong Key Lab Marine Mat Med, Guangzhou 510301, Peoples R China
关键词
-Terthienyl; Prostate cancer; Androgen receptor; Protein kinase B; P27; Proliferation; Apoptosis; ALPHA-TERTHIENYL; GROWTH; P27;
D O I
10.1016/j.biopha.2022.113266
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Prostate cancer is a disease that often occurs in elderly men. Androgen receptor signaling pathway runs through the occurrence and development of prostate cancer. Thereby, targeting androgen receptor is a crucial strategy for the treatment of prostate cancer. alpha-Terthienyl, which has been used as photosensitive activator and insecticide, is a natural compound rich in marigold. In the present study, we found alpha-terthienyl could inhibit the cell viability of four prostate cancer cell lines, especially on LNCaP and 22Rv1 cells which endogenously express androgen receptor. Then we proved that it could inhibit the proliferation of prostate cancer cells and induce apoptosis of prostate cancer cells by plate clone formation assay and flow cytometry respectively. Furthermore, we found alpha-terthienyl could inhibit androgen receptor nuclear translocation, reduce androgen receptor expression, reduce the mRNA and protein expression of androgen receptor target genes (KLK3, TMPRSS2, PCA3) and nuclear proliferation antigen Ki67 and PCNA. In addition, it inhibited the expression and phosphorylation of Akt protein while increasing the expression of tumor suppressor p27. Besides, we constructed a mouse xenograft prostate cancer model and confirmed that alpha-terthienyl also inhibited the growth of prostate cancer in vivo. In conclusively, alpha-terthienyl played an anti-prostate cancer role by inhibiting both the expression of androgen receptor and the transduction of its signal pathway, suggesting that it is a promising natural small molecule for the treatment of prostate cancer.
引用
收藏
页数:10
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