Differential effects of protein kinase C-eta on apoptosis versus senescence

Alakananda Basu, Deepanwita Pal, Rachel Blaydes

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Protein kinase C-eta (PKCη) is considered an anti-apoptotic kinase, which promotes cell survival and chemoresistance in several cancers, including breast cancer. We have recently shown that PKCη positively regulates the anti-apoptotic protein Mcl-1 in breast cancer cells, and depletion of PKCη induced proteasomal degradation of Mcl-1. We therefore examined if depletion of PKCη would enhance cellular sensitivity to chemotherapeutic agents. Silencing of PKCη by siRNA attenuated apoptosis induced by doxorubicin and paclitaxel in both MCF-7 and T47D breast cancer cells. While silencing of Mcl-1 caused a substantial increase in apoptosis induced by doxorubicin, the combined knockdown of PKCη and Mcl-1 was less effective. Depletion of PKCη also caused an increase in the abundance of the cell cycle inhibitor p27 and a decrease in the clonogenic survival of MCF-7 and T47D cells. PKCη knockdown was associated with an increase in senescence-associated β-galactosidase (SA-β-gal) activity but this increase was attenuated by knockdown of p27. The suppression of doxorubicin-induced apoptosis by PKCη knockdown was partially relieved when p27 was depleted. Since loss of proliferative capacity during senescence could cause resistance to chemotherapeutic drugs, our results suggest that PKCη knockdown inhibits apoptosis by inducing p27-mediated senescence.

Original languageEnglish
Pages (from-to)1-7
Number of pages7
JournalCellular Signalling
Volume55
DOIs
StatePublished - 1 Mar 2019

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Apoptosis
Doxorubicin
Breast Neoplasms
protein kinase C eta
Galactosidases
Apoptosis Regulatory Proteins
MCF-7 Cells
Paclitaxel
Small Interfering RNA
Cell Survival
Cell Cycle
Phosphotransferases
Pharmaceutical Preparations

Keywords

  • Apoptosis
  • Mcl-1
  • PKCη
  • Senescence
  • p27

Cite this

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abstract = "Protein kinase C-eta (PKCη) is considered an anti-apoptotic kinase, which promotes cell survival and chemoresistance in several cancers, including breast cancer. We have recently shown that PKCη positively regulates the anti-apoptotic protein Mcl-1 in breast cancer cells, and depletion of PKCη induced proteasomal degradation of Mcl-1. We therefore examined if depletion of PKCη would enhance cellular sensitivity to chemotherapeutic agents. Silencing of PKCη by siRNA attenuated apoptosis induced by doxorubicin and paclitaxel in both MCF-7 and T47D breast cancer cells. While silencing of Mcl-1 caused a substantial increase in apoptosis induced by doxorubicin, the combined knockdown of PKCη and Mcl-1 was less effective. Depletion of PKCη also caused an increase in the abundance of the cell cycle inhibitor p27 and a decrease in the clonogenic survival of MCF-7 and T47D cells. PKCη knockdown was associated with an increase in senescence-associated β-galactosidase (SA-β-gal) activity but this increase was attenuated by knockdown of p27. The suppression of doxorubicin-induced apoptosis by PKCη knockdown was partially relieved when p27 was depleted. Since loss of proliferative capacity during senescence could cause resistance to chemotherapeutic drugs, our results suggest that PKCη knockdown inhibits apoptosis by inducing p27-mediated senescence.",
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Differential effects of protein kinase C-eta on apoptosis versus senescence. / Basu, Alakananda; Pal, Deepanwita; Blaydes, Rachel.

In: Cellular Signalling, Vol. 55, 01.03.2019, p. 1-7.

Research output: Contribution to journalArticle

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