Induction of apoptosis in human DU145 prostate cancer cells by KHC-4 treatment
Tien-Huang Lin1, Wen-Chi Chen, Hsi-Chin Wu
1Division of Urology, Division of Urology, Taichung Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan, Republic of China.
Abstract:
Prostate cancer (CaP) is one of the most prevalent cancers worldwide and the incidence and mortality rates have been rapidly increasing in recent years in Taiwan. Therefore, it is important to development anti-cancer therapy. In this study, KHC-4 was identified from 2-phenyl-4-quionolone derivatives in human prostate cancer cells and as a potential antitumor agent. In this study, we have identified KHC-4 induced apoptosis effects in castration-resistant prostate cancer DU145 cells, and the IC₅₀ value of KHC-4 was 0.1 μM. KHC-4 suppressed the survival signaling p-PI3K and p-Akt and protein levels of Bcl-2 and Bcl-xL, upregulated Bax, cytochrome c and Caspase 8/9 and induced apoptosis by mitochondrial-dependent pathway. In JC-1 assay monitored the loss of membrane potential in KHC-4 treatments. TUNEL assay results showed DNA fragmentation in KHC-4 induced apoptosis. We concluded that KHC-4 exerted anti-tumor effects in DU145 cells by induction of apoptosis.
Insights
KHC-4, a novel compound, effectively triggers apoptosis in castration-resistant prostate cancer cells. This research highlights KHC-4 as a promising agent for developing new prostate cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate cancer (CaP) is a globally prevalent malignancy with rising incidence and mortality rates, particularly in Taiwan.
- There is an urgent need for the development of novel anti-cancer therapies to combat this disease.
- 2-phenyl-4-quionolone derivatives represent a class of compounds with potential antitumor activity.
Purpose of the Study:
- To investigate the anti-tumor effects of KHC-4, a novel 2-phenyl-4-quionolone derivative.
- To determine the mechanism by which KHC-4 exerts its anti-cancer effects in human prostate cancer cells.
- To evaluate KHC-4 as a potential therapeutic agent for castration-resistant prostate cancer.
Main Methods:
- KHC-4 was tested on castration-resistant prostate cancer DU145 cells.
- Apoptosis induction was assessed using various assays, including TUNEL assay and JC-1 assay to monitor membrane potential.
- Western blotting was employed to analyze the expression of key proteins involved in apoptosis signaling pathways (e.g., PI3K/Akt, Bcl-2 family, Caspases).
Main Results:
- KHC-4 demonstrated significant anti-tumor effects, inducing apoptosis in DU145 cells with an IC₅₀ value of 0.1 μM.
- KHC-4 suppressed pro-survival signaling pathways, including p-PI3K and p-Akt.
- Upregulation of pro-apoptotic proteins (Bax, cytochrome c, Caspase 8/9) and downregulation of anti-apoptotic proteins (Bcl-2, Bcl-xL) were observed, indicating mitochondrial-dependent apoptosis.
- Loss of mitochondrial membrane potential and DNA fragmentation were confirmed by JC-1 and TUNEL assays, respectively.
Conclusions:
- KHC-4 effectively induces apoptosis in castration-resistant prostate cancer DU145 cells.
- The anti-tumor mechanism of KHC-4 involves the mitochondrial-dependent apoptosis pathway.
- KHC-4 shows significant potential as an anti-cancer therapeutic agent for prostate cancer.
