Skip to main content
SpringerLink
Log in

Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling

  • Original Article
  • Published:
Chinese Journal of Cancer Research

Abstract

Anacardic acid (AA) is a mixture of 2-hydroxy-6-alkylbenzoic acid homologs. It is widely regarded as a non-specific histone acetyltransferase inhibitor of p300. The effects and the mechanisms of AA in LNCaP cells (prostate cancer cells) remain unknown. To investigate the effect of AA on LNCaP cells, we had carried out several experiments and found that AA inhibits LNCaP cell proliferation, induces G1/S cell cycle arrest and apoptosis of LNCaP cell. The mechanisms via which AA acts on LNCaP cells may be due to the following aspects. First, AA can regulate p300 transcription and protein level except for its mechanisms regulating function of p300 through post-translational modification in LNCaP cells. Second, AA can activate p53 through increasing the phosphorylation of p53 on Ser15 in LNCaP cells. AA can selectively activate p21 (target genes of p53). Third, AA can down-regulates androgen receptor (AR) through supressing p300. Our study suggests that AA has multiple anti-tumor activities in LNCaP cells and warrants further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Gururajan M, Posadas EM, Chung LW. Future perspectives of prostate cancer therapy. Transl Androl Urol 2012;1:19–32.

    PubMed  Google Scholar 

  2. Britto AC, de Oliveira AC, Henriques RM, et al. In vitro and in vivo antitumor effects of the essential oil from the leaves of Guatteria friesiana. Planta Med 2012;78:409–414.

    Article  PubMed  CAS  Google Scholar 

  3. de Melo JG, Santos AG, de Amorim EL, et al. Medicinal plants used as antitumor agents in Brazil: an ethnobotanical approach. Evid Based Complement Alternat Med 2011;2011:365359.

    PubMed  Google Scholar 

  4. Sowmyalakshmi S, Nur-E-Alam M, Akbarsha MA, et al. Investigation on Semecarpus Lehyam—a Siddha medicine for breast cancer. Planta 2005;220:910–918.

    Article  PubMed  CAS  Google Scholar 

  5. Rea AI, Schmidt JM, Setzer WN, et al. Cytotoxic activity of Ozoroa insignis from Zimbabwe. Fitoterapia 2003;74:732–735.

    Article  PubMed  CAS  Google Scholar 

  6. Devipriya B, Kumaradhas P. Probing the effect of intermolecular interaction and understanding the electrostatic moments of anacardic acid in the active site of p300 enzyme via DFT and charge density analysis. J Mol Graph Model 2012;34:57–66.

    Article  PubMed  CAS  Google Scholar 

  7. Sukumari-Ramesh S, Singh N, Jensen MA, et al. Anacardic acid induces caspase-independent apoptosis and radiosensitizes pituitary adenoma cells. J Neurosurg 2011;114:1681–1690.

    Article  PubMed  CAS  Google Scholar 

  8. Hemshekhar M, Sebastin Santhosh M, Kemparaju K, et al. Emerging Roles of Anacardic Acid and Its Derivatives: A Pharmacological Overview. Basic Clin Pharmacol Toxicol 2011. [Epub ahead of print].

    Google Scholar 

  9. Cui L, Miao J, Furuya T, et al. Histone acetyltransferase inhibitor anacardic acid causes changes in global gene expression during in vitro Plasmodium falciparum development. Eukaryot Cell 2008;7:1200–1210.

    Article  PubMed  CAS  Google Scholar 

  10. Ghizzoni M, Boltjes A, Graaf C, et al. Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative. Bioorg Med Chem 2010;18:5826–5834.

    Article  PubMed  CAS  Google Scholar 

  11. Sun Y, Jiang X, Chen S, et al. Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation. FEBS Lett 2006;580:4353–4356.

    Article  PubMed  CAS  Google Scholar 

  12. Souto JA, Benedetti R, Otto K, et al. New anacardic acidinspired benzamides: histone lysine acetyltransferase activators. Chem Med Chem 2010;5:1530–1540.

    PubMed  CAS  Google Scholar 

  13. Souto JA, Conte M, Alvarez R, et al. Synthesis of benzamides related to anacardic acid and their histone acetyltransferase (HAT) inhibitory activities. Chem Med Chem 2008;3:1435–1442.

    PubMed  CAS  Google Scholar 

  14. Sung B, Pandey MK, Ahn KS, et al. Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-kappaB-regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-kappaBalpha kinase, leading to potentiation of apoptosis. Blood 2008;111:4880–4891.

    Article  PubMed  CAS  Google Scholar 

  15. Schultz DJ, Wickramasinghe NS, Ivanova MM, et al. Anacardic acid inhibits estrogen receptor alpha-DNA binding and reduces target gene transcription and breast cancer cell proliferation. Mol Cancer Ther 2010;9:594–605.

    Article  PubMed  CAS  Google Scholar 

  16. Lee C, Zhang Q, Zi X, et al. TGF-β mediated DNA methylation in prostate cancer. Transl Androl Urol 2012;1:78–88.

    Google Scholar 

  17. Ameri A, Alidoosti A, Hosseini Y, et al. Prognostic value of promoter hypermethylation of Retinoic Acid Receptor Beta (RARB) and CDKN2 (p16/MTS1) in prostate cancer. Chin J Cancer Res 2011;23:306–311.

    Article  PubMed  CAS  Google Scholar 

  18. Ilic D, Forbes KM, Hassed C. Lycopene for the prevention of prostate cancer. Cochrane Database Syst Rev 2011;11:CD008007.

    PubMed  Google Scholar 

  19. Namiki M, Ueno S, Kitagawa Y. Role of hormonal therapy for prostate cancer: perspective from Japanese experiences. Transl Androl Urol 2012;1:160–172.

    Google Scholar 

  20. Wolff JM, Schmid HP. Extension of the therapeutic spectrum in castration-resistant prostate cancer: Osteoclast inhibition with denosumab. Transl Androl Urol 2012;1:118–119.

    Google Scholar 

  21. Palozza P, Colangelo M, Simone R, et al. Lycopene induces cell growth inhibition by altering mevalonate pathway and Ras signaling in cancer cell lines. Carcinogenesis 2010;31:1813–1821.

    Article  PubMed  CAS  Google Scholar 

  22. Limpens J, Schröder FH, de Ridder CM, et al. Combined lycopene and vitamin E treatment suppresses the growth of PC-346C human prostate cancer cells in nude mice. J Nutr 2006;136:1287–1293.

    PubMed  CAS  Google Scholar 

  23. Chun JY, Tummala R, Nadiminty N, et al. Andrographolide, an herbal medicine, inhibits interleukin-6 expression and suppresses prostate cancer cell growth. Genes Cancer 2010;1:868–876.

    Article  PubMed  CAS  Google Scholar 

  24. Sung B, Pandey MK, Ahn KS, et al. Anacardic acid (6-nonadecyl salicylic acid), an inhibitor of histone acetyltransferase, suppresses expression of nuclear factor-kappaB-regulated gene products involved in cell survival, proliferation, invasion, and inflammation through inhibition of the inhibitory subunit of nuclear factor-kappaBalpha kinase, leading to potentiation of apoptosis. Blood 2008;111:4880–4891.

    Article  PubMed  CAS  Google Scholar 

  25. Karamouzis MV, Konstantinopoulos PA, Papavassiliou AG. Roles of CREB-binding protein (CBP)/p300 in respiratory epithelium tumorigenesis. Cell Res 2007;17:324–332.

    Article  PubMed  CAS  Google Scholar 

  26. Demarest SJ, Martinez-Yamout M, Chung J, et al. Mutual synergistic folding in recruitment of CBP/p300 by p160 nuclear receptor coactivators. Nature 2002;415:549–553.

    Article  PubMed  CAS  Google Scholar 

  27. Wang X, Pan L, Feng Y, et al. p300 plays a role in p16(INK4a) expression and cell cycle arrest. Oncogene 2008;27:1894–1904.

    Article  PubMed  CAS  Google Scholar 

  28. Luo J, Li M, Tang Y, et al. Acetylation of p53 augments its site-specific DNA binding both in vitro and in vivo. Proc Natl Acad Sci U S A 2004;101:2259–2264.

    Article  PubMed  CAS  Google Scholar 

  29. Pan X, Zhao J, Zhang WN, et al. Induction of SOX4 by DNA damage is critical for p53 stabilization and function. Proc Natl Acad Sci U S A 2009;106:3788–3793.

    Article  PubMed  CAS  Google Scholar 

  30. Livengood JA, Scoggin KE, Van Orden K, et al. p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300. J Biol Chem 2002;277:9054–9061.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Urology, the third Xiangya Hospital of Xiangya Medical College, Central South University, Changsha, 410013, China

    Jing Tan, Binghai Chen, Leye He, Yuxin Tang, Zhiqiang Jiang, Guangmin Yin, Jinrong Wang & Xianzhen Jiang

Authors
  1. Jing Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Binghai Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leye He
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuxin Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhiqiang Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Guangmin Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Jinrong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Xianzhen Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Xianzhen Jiang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, J., Chen, B., He, L. et al. Anacardic acid (6-pentadecylsalicylic acid) induces apoptosis of prostate cancer cells through inhibition of androgen receptor and activation of p53 signaling. Chin. J. Cancer Res. 24, 275–283 (2012). https://doi.org/10.1007/s11670-012-0264-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11670-012-0264-y

Key Words

Search

Navigation