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Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis

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Abstract

Purpose

Curcumin is a potent antitumor agent. The objective of this study was to explore the interaction between curcumin and PGK1, an oncogene in the FOXD3/miR-143 axis, in prostate cancer therapy.

Methods

MiRNA microarray analysis was used to identify miRNAs upregulated by curcumin treatment. MiR-143 was dramatically upregulated by curcumin. Cells were treated with antimiR-143 in combination to curcumin, followed by examining cell viability and migration. Bioinformatics analysis was used to investigate target genes of miR-143. The interaction between miR-143 and PGK1 was evaluated with dual-luciferase assay. Since FOXD3 is important in the regulation of miR-143, we explored whether curcumin regulated FOXD3 expression. FOXD3 was also ectopically overexpressed to investigate its effects on curcumin’s regulation of miR-143.

Results

Curcumin treatment significantly upregulated miR-143 and decreased prostate cancer cell proliferation and migration. Those effects were attenuated by anti-miR-143 transfection. Both miR-143 overexpression and curcumin treatment inhibited PGK1 expression and ectopic expression of PGK1 antagonized curcumin’s antitumor effects. FOXD3 was upregulated by miR-143. Ectopic expression of FOXD3 synergized with curcumin in upregulating miR-143 expression.

Conclusion

Curcumin inhibits prostate cancer by upregulating miR-143. PGK1 is downregulated by miR-143, and FOXD3 upregulation is essential for the antitumor effect of curcumin.

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Acknowledgements

This study was supported by Project for Key Disease Type of Chinese and Western Integrative Medicine, Shanghai Municipal Commission of Heath and Family Planning: Special Subject Construction of Treating Prostatic Cancer by Chinese and Western Integrative Medicine (Subject Number: ZXBZ2012-07); Project of Establishing Working Studio of Shanghai Doctor of Traditional Chinese Medicine, Zhou Zhiheng (Subject Number: ZYSNXD-CC-MZY011); The three year plan of Shanghai to further accelerate the development of traditional Chinese Medicine (No: ZY3-RCPY-3-1012). We thank Shanghai Doctor of Traditional Chinese Medicine, Professor Zhiheng Zhou for his help.

Author contributions

HWC, HJY, and YGF carried out the experiments, participated in the statistical analysis, and drafted the manuscript; FL and LC conceived of the study, and participated in its design and coordination, and helped to draft the manuscript.

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    Authors and Affiliations

    1. Surgical Department I (Urology Department), Shanghai University of Traditional Chinese Medicine Affiliated LONGHUA Hospital, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China

      Hongwen Cao, Yigeng Feng & Lei Chen

    2. Oncology Department of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine Affiliated PUTUO Hospital, No. 164 Lanxi Road, Putuo District, Shanghai, 200062, China

      Hongjie Yu & Fang Liang

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    1. Hongwen Cao
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    Correspondence to Lei Chen or Fang Liang.

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    This study was supported by Project for Key Disease Type of Chinese and Western Integrative Medicine, Shanghai Municipal Commission of Heath and Family Planning: Special Subject Construction of Treating Prostatic Cancer by Chinese and Western Integrative Medicine (Subject Number: ZXBZ2012-07); Project of Establishing Working Studio of Shanghai Doctor of Traditional Chinese Medicine, Zhou Zhiheng (Subject Number: ZYSNXD-CC-MZY011); The three year plan of Shanghai to further accelerate the development of traditional Chinese Medicine (No: ZY3-RCPY-3-1012).

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    Hongwen Cao, Hongjie Yu, and Yigeng Feng contributed equally.

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    Cao, H., Yu, H., Feng, Y. et al. Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis. Cancer Chemother Pharmacol 79, 985–994 (2017). https://doi.org/10.1007/s00280-017-3301-1

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