Open Access

Inhibition of atypical protein kinase C‑ι effectively reduces the malignancy of prostate cancer cells by downregulating the NF-κB signaling cascade

  • Authors:
    • André H. Apostolatos
    • Wishrawana S. Ratnayake
    • Hla Win-Piazza
    • Christopher A. Apostolatos
    • Tracess Smalley
    • Loveleen Kang
    • Raoul Salup
    • Robert Hill
    • Mildred Acevedo-Duncan
  • View Affiliations

  • Published online on: August 28, 2018     https://doi.org/10.3892/ijo.2018.4542
  • Pages: 1836-1846
  • Copyright: © Apostolatos et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Prostate cancer (PC) is the most common type of cancer among men. Aggressive and metastatic PC results in life-threatening tumors, and represents one of the leading causes of mortality in men. Previous studies of atypical protein kinase C isoforms (aPKCs) have highlighted its role in the survival of cultured prostate cells via the nuclear factor (NF)-κB pathway. The present study showed that PKC‑ι was overexpressed in PC samples collected from cancer patients but not in non-invasive prostate tissues, indicating PKC‑ι as a possible prognostic biomarker for the progression of prostate carcinogenesis. Immunohistochemical staining further confirmed the association between PKC‑ι and the prostate malignancy. The DU‑145 and PC‑3 PC cell lines, and the non-neoplastic RWPE‑1 prostatic epithelial cell line were cultured and treated with aPKC inhibitors 2‑acetyl‑1,3-cyclopentanedione (ACPD) and 5-amino‑1-(1R,2S,3S,4R)-2,3-dihydroxy-4-methylcyclopentyl)‑1H-imidazole-4-carboxamide (ICA‑1). Western blot data demonstrated that ICA‑1 was an effective and specific inhibitor of PKC‑ι and that ACPD inhibited PKC‑ι and PKC‑ζ. Furthermore, the two inhibitors significantly decreased malignant cell proliferation and induced apoptosis. The inhibitors showed no significant cytotoxicity towards the RWPE‑1 cells, but exhibited cytostatic effects on the DU‑145 and PC‑3 cells prior to inducing apoptosis. The inhibition of aPKCs significantly reduced the translocation of NF-κB to the nucleus. Furthermore, this inhibition promoted apoptosis, reduced signaling for cell survival, and reduced the proliferation of PC cells, whereas the normal prostate epithelial cells were relatively unaffected. Overall, the results suggested that PKC‑ι and PKC‑ζ are essential for the progression of PC, and that ACPD and ICA‑1 can be effectively used as potential inhibitors in targeted therapy.
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November-2018
Volume 53 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Apostolatos AH, Ratnayake WS, Win-Piazza H, Apostolatos CA, Smalley T, Kang L, Salup R, Hill R and Acevedo-Duncan M: Inhibition of atypical protein kinase C‑ι effectively reduces the malignancy of prostate cancer cells by downregulating the NF-κB signaling cascade. Int J Oncol 53: 1836-1846, 2018
APA
Apostolatos, A.H., Ratnayake, W.S., Win-Piazza, H., Apostolatos, C.A., Smalley, T., Kang, L. ... Acevedo-Duncan, M. (2018). Inhibition of atypical protein kinase C‑ι effectively reduces the malignancy of prostate cancer cells by downregulating the NF-κB signaling cascade. International Journal of Oncology, 53, 1836-1846. https://doi.org/10.3892/ijo.2018.4542
MLA
Apostolatos, A. H., Ratnayake, W. S., Win-Piazza, H., Apostolatos, C. A., Smalley, T., Kang, L., Salup, R., Hill, R., Acevedo-Duncan, M."Inhibition of atypical protein kinase C‑ι effectively reduces the malignancy of prostate cancer cells by downregulating the NF-κB signaling cascade". International Journal of Oncology 53.5 (2018): 1836-1846.
Chicago
Apostolatos, A. H., Ratnayake, W. S., Win-Piazza, H., Apostolatos, C. A., Smalley, T., Kang, L., Salup, R., Hill, R., Acevedo-Duncan, M."Inhibition of atypical protein kinase C‑ι effectively reduces the malignancy of prostate cancer cells by downregulating the NF-κB signaling cascade". International Journal of Oncology 53, no. 5 (2018): 1836-1846. https://doi.org/10.3892/ijo.2018.4542