Induction of apoptosis in human DU145 prostate cancer cells by KHC-4 treatment.
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.
Division of Urology, Division of Urology, Taichung Tzu Chi Hospital, The Buddhist Tzu Chi Medical Foundation, Taichung 42743, Taiwan, Republic of China.
Tien-Huang
TH
Lin
Wen-Chi
WC
Chen
Hsi-Chin
HC
Wu
Wen-Shin
WS
Chien
Shang-Seu
SS
Lee
Fu-Jenn
FJ
Tsai
Chang-Hai
CH
Tsai
Wei-Jen
WJ
Ting
Sheng-Chu
SC
Kuo
Chih-Yang
CY
Huang
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015363:Quinolones / Q000494:pharmacology*
C577043:2'-fluoro-6-morpholinyl-2-phenyl-4-quinolone; D000970:Antineoplastic Agents; D009025:Morpholines; D015363:Quinolones; D020169:Caspases