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Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression

  • Authors:
    • Rekha Patel
    • SM Anisul Islam
    • Raja Reddy Bommareddy
    • Tracess Smalley
    • Mildred Acevedo‑Duncan
  • View Affiliations / Copyright

    Affiliations: Department of Chemistry, University of South Florida, Tampa, FL 33620, USA
    Copyright: © Patel et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1373-1386
    |
    Published online on: March 20, 2020
       https://doi.org/10.3892/ijo.2020.5021
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Abstract

Despite enormous scientific advancements in cancer treatment, there is a need for research to combat cancer, particularly bladder cancer. Drugs once proved to be effective in treating bladder cancer have shown reduced efficacy; hence, the cancer recurrence rate is increasing. To overcome this situation, several strategies have been considered, including the development of novel active drugs or modification of existing therapeutic regimens by combining two or more existing drugs. In recent years, atypical protein kinase Cs (PKCs), phospholipid‑dependent serine/threonine kinases, have been considered as a central regulator of various cancer‑associated signaling pathways, and they control cell cycle progression, tumorigenesis and metastasis. Additionally, the biologically crucial mTOR signaling pathway is altered in numerous types of cancer, including bladder cancer. Furthermore, despite independent activation, atypical PKC signaling can be triggered by mTOR. The present study examined whether the concurrent inhibition of atypical PKCs and mTOR using a combination of novel atypical PKC inhibitors (ICA‑I, an inhibitor of PKC‑ι; or ζ‑Stat, an inhibitor of PKC‑ζ) and rapamycin blocks bladder cancer progression. In the present study, healthy bladder MC‑SV‑HUCT2 and bladder cancer TCCSUP cells were tested and subjected to a WST1 assay, western blot analysis, immunoprecipitation, a scratch wound healing assay, flow cytometry and immunofluorescence analyses. The results revealed that the combination therapy induced a reduction in human bladder cancer cell viability compared with control and individual atypical PKC inhibitor and rapamycin treatment. Additionally, the concurrent inhibition of atypical PKCs and mTOR retards the migration of bladder cancer cells. These findings indicated that the administration of atypical PKC inhibitors together with rapamycin could be a useful therapeutic option in treating bladder cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Patel R, Islam S, Bommareddy RR, Smalley T and Acevedo‑Duncan M: Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression. Int J Oncol 56: 1373-1386, 2020.
APA
Patel, R., Islam, S., Bommareddy, R.R., Smalley, T., & Acevedo‑Duncan, M. (2020). Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression. International Journal of Oncology, 56, 1373-1386. https://doi.org/10.3892/ijo.2020.5021
MLA
Patel, R., Islam, S., Bommareddy, R. R., Smalley, T., Acevedo‑Duncan, M."Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression". International Journal of Oncology 56.6 (2020): 1373-1386.
Chicago
Patel, R., Islam, S., Bommareddy, R. R., Smalley, T., Acevedo‑Duncan, M."Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression". International Journal of Oncology 56, no. 6 (2020): 1373-1386. https://doi.org/10.3892/ijo.2020.5021
Copy and paste a formatted citation
x
Spandidos Publications style
Patel R, Islam S, Bommareddy RR, Smalley T and Acevedo‑Duncan M: Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression. Int J Oncol 56: 1373-1386, 2020.
APA
Patel, R., Islam, S., Bommareddy, R.R., Smalley, T., & Acevedo‑Duncan, M. (2020). Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression. International Journal of Oncology, 56, 1373-1386. https://doi.org/10.3892/ijo.2020.5021
MLA
Patel, R., Islam, S., Bommareddy, R. R., Smalley, T., Acevedo‑Duncan, M."Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression". International Journal of Oncology 56.6 (2020): 1373-1386.
Chicago
Patel, R., Islam, S., Bommareddy, R. R., Smalley, T., Acevedo‑Duncan, M."Simultaneous inhibition of atypical protein kinase‑C and mTOR impedes bladder cancer cell progression". International Journal of Oncology 56, no. 6 (2020): 1373-1386. https://doi.org/10.3892/ijo.2020.5021
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