Related Experiment Video
Updated: Jun 6, 2026
Evaluating the Differentiation Capacity of Mouse Prostate Epithelial Cells Using Organoid Culture
Published on: November 22, 2019
Differential sensitization of different prostate cancer cells to apoptosis
Jinjin Guo1, Tongbo Zhu, Lihua Chen
1Department of Radiation Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Abstract:
Although protein kinase C (PKC) plays an important role in sensitizing prostate cancer cells to apoptosis, and suppression of PKC is able to trigger an apoptotic crisis in cells harboring oncogenic ras, little is known about whether dyregulation of Ras effectors in prostate cancer cells, together with loss of PKC, is synthetically lethal. The current study aims at investigating whether prostate cancer cells with aberrant Ras effector signaling are sensitive to treatment with HMG (a PKC inhibitor) for the induction of apoptosis. We show that prostate cancer DU145 cells expressing a high level of JNK1 become susceptible to apoptosis after treatment with HMG, in which caspase 8 is activated and cytochrome c is released to the cytosol. In contrast, the addition of HMG sensitizes LNCaP or PC3 prostate cancer cells harboring an active Akt to apoptosis, in which ROS is upregulated to induce the UPR and GADD153 expression. The concurrent activation of JNK1 and Akt has an additive effect on apoptosis following PKC suppression. Thus, the data identify Akt and JNK1 as potential targets in prostate cancer cells for PKC inhibition-induced apoptosis.
Insights
Prostate cancer cells with dysregulated Ras pathways undergo apoptosis when protein kinase C (PKC) is inhibited. This study identifies JNK1 and Akt as key targets for inducing apoptosis in prostate cancer via PKC suppression.
Area of Science:
- Oncology
- Molecular Biology
- Cellular Signaling
Background:
- Protein kinase C (PKC) is crucial for sensitizing prostate cancer cells to apoptosis.
- Suppression of PKC can induce apoptosis in cells with oncogenic Ras.
- The synthetic lethality of Ras effector dysregulation combined with PKC loss in prostate cancer is poorly understood.
Purpose of the Study:
- To investigate if prostate cancer cells with aberrant Ras effector signaling are sensitive to apoptosis induction by HMG, a PKC inhibitor.
- To explore the role of specific Ras effectors, JNK1 and Akt, in apoptosis following PKC inhibition.
Main Methods:
- Treatment of prostate cancer cell lines (DU145, LNCaP, PC3) with HMG.
- Analysis of apoptosis induction pathways, including caspase 8 activation, cytochrome c release, reactive oxygen species (ROS) upregulation, unfolded protein response (UPR), and GADD153 expression.
- Assessment of JNK1 and Akt activation levels.
Main Results:
- HMG treatment induced apoptosis in DU145 cells with high JNK1, involving caspase 8 activation and cytochrome c release.
- HMG treatment sensitized LNCaP and PC3 cells with active Akt to apoptosis via ROS upregulation, UPR, and GADD153 expression.
- Concurrent activation of JNK1 and Akt showed an additive effect on apoptosis after PKC suppression.
Conclusions:
- Prostate cancer cells with aberrant Ras effector signaling are sensitive to PKC inhibition-induced apoptosis.
- JNK1 and Akt are identified as potential therapeutic targets in prostate cancer for enhancing apoptosis through PKC inhibition.
Related Concept Videos
01:17The Extrinsic Apoptotic Pathway
01:31The Intrinsic Apoptotic Pathway