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Apoptotic effect of tolfenamic acid in androgen receptor-independent prostate cancer cell and xenograft tumor through specificity protein 1

  1. Eun-Sun Choi1,†,
  2. Jung-Hyun Shim2,†,
  3. Ji-Youn Jung3,
  4. Hyeong-Jin Kim3,
  5. Kyeong-Hee Choi1,
  6. Ji-Ae Shin1,
  7. Jeong-Seok Nam4,
  8. Nam-Pyo Cho1,*,
  9. Sung-Dae Cho1,*

Article first published online: 17 FEB 2011

DOI: 10.1111/j.1349-7006.2011.01871.x

Issue

Cancer Science

Cancer Science

Volume 102, Issue 4, pages 742–748, April 2011

Additional Information

How to Cite

Choi, E.-S., Shim, J.-H., Jung, J.-Y., Kim, H.-J., Choi, K.-H., Shin, J.-A., Nam, J.-S., Cho, N.-P. and Cho, S.-D. (2011), Apoptotic effect of tolfenamic acid in androgen receptor-independent prostate cancer cell and xenograft tumor through specificity protein 1. Cancer Science, 102: 742–748. doi: 10.1111/j.1349-7006.2011.01871.x

Author Information

  1. 1

    Department of Oral Pathology, School of Dentistry and Institute of Oral Bioscience, Brain Korea 21 Project, Chonbuk National University, Jeon-ju

  2. 2

    Department of Biochemistry, College of Medicine, Soonchunhyang University, Cheonan

  3. 3

    Department of Companion and Laboratory Animal Science, Kongju National University, Yesan

  4. 4

    Lee Gil Ya Cancer and Diabetes Institute, Gachon University of Medicine and Science, Inchon, Korea

  1. †

    These authors contributed equally to this paper.

* To whom correspondence should be addressed. E-mails: efiwdsc@chonbuk.ac.kr; npcho@chonbuk.ac.kr

  1. †

    These authors contributed equally to this paper.

Publication History

  1. Issue published online: 18 MAR 2011
  2. Article first published online: 17 FEB 2011
  3. Accepted manuscript online: 17 JAN 2011 09:49AM EST
  4. (Received August 30, 2010/Revised December 22, 2010/Accepted January 9, 2011/Accepted manuscript online January 17, 2011)

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Tolfenamic acid (Tol) is a non-steroidal anti-inflammatory drug that was reported to exhibit anticancer activity in pancreatic and colorectal cancer models. This study examined the role of Tol in the death regulation of PC-3 and DU145 human androgen-independent prostate cancer cells. The results showed that Tol inhibited cell growth and induced apoptosis, as evidenced by nuclear fragmentation and cleaved caspase 3 and poly(ADP-ribose) polymerase. Tol suppressed the specificity protein 1 (Sp1) protein in both PC-3 and DU145 cells. Tol also attenuated Sp1 mRNA and its promoter activity in DU145 cells, but did not alter them in PC-3 cells, indicating that Tol degrades Sp1 protein in these cells. Tol also downregulated protein levels, mRNA levels and promoter activities of survivin and myeloid cell leukemia-1, which are downstream targets of Sp1. The expressions of survivin and Mcl-1 and cancer cell growth were lower in the PC-3 cells treated with Sp1 interfering RNA and mithramycin A. Moreover, an oral injection of Tol decreased tumor growth and downregulated the Sp1 protein in athymic nude mice bearing DU145 cell xenografts without hepatotoxicity. Overall, Tol downregulates the Sp1 protein to inhibit growth and induce apoptosis in androgen-refractory prostate cancers, both in vitro and in vivo, that show resistance against many chemotherapeutic agents. (Cancer Sci 2011; 102: 742–748)

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