OncoTargets and Therapy (May 2016)

Luteolin inhibited proliferation and induced apoptosis of prostate cancer cells through miR-301

  • Han K,
  • Meng W,
  • Zhang JJ,
  • Zhou Y,
  • Wang YL,
  • Su Y,
  • Lin SC,
  • Gan ZH,
  • Sun YN,
  • Min DL

Journal volume & issue
Vol. 2016, no. Issue 1
pp. 3085 – 3094

Abstract

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Kun Han,1,* Wei Meng,2,* Jian-jun Zhang,1 Yan Zhou,1 Ya-ling Wang,1 Yang Su,1 Shu-chen Lin,1 Zhi-hua Gan,1 Yong-ning Sun,1 Da-liu Min11Oncology Department, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, 2Institute of Genetic Engineering of Southern Medical University, Guangzhou, Guangdong, People’s Republic of China*These authors contributed equally to this workAbstract: Luteolin is a falvonoid compound derived from Lonicera japonica Thunb. Numerous reports have demonstrated that luteolin has anticancer effects on many kinds of tumors. This study investigated the effects of luteolin on prostate cancer (PCa), assessing the PC3 and LNCaP cells. The cell viability and apoptosis were assessed by performing Cell Counting Kit-8 assay and Annexin V–fluorescein isothiocyanate/propidium iodide double staining. Luteolin was found to inhibit androgen-sensitive and androgen-independent PCa cell lines’ growth and induced apoptosis. To uncover the exact mechanisms and molecular targets, microRNA (miR) array analysis was performed. miR-301 was found to be markedly downregulated. Then, the expression of miR-301 was retrospectively analyzed in the primary PCa tissues by quantitative reverse transcription polymerase chain reaction and in situ hybridization methods. According to the quantitative reverse transcription polymerase chain reaction results of miR-301, the 54 PCa patients were divided into two groups: high and low miR-301 groups. The division indicator is a relative expression ≥5. Compared to the low-expression group, high miR-301 expression was associated with a significantly shorter overall survival (P=0.029). The proapoptotic gene, DEDD2, was predicted to be the direct target of miR-301. It was clarified in accordance with bioinformatics and luciferase activity analyses. The overexpression of miR-301 by plasmid decreased the luteolin effect. Taken together, these results suggest that luteolin inhibits PCa cell proliferation through miR-301, the poor predictive factor of PCa.Keywords: luteolin, prostate cancer, miR-301, DEDD2, apoptosis

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