FCX, an arylidene derivative, induces apoptosis in androgen receptor-selective prostate cancer cells
Rajagopalan Prasanna1, Ashraf A Elbessoumy2, Harish C Chandramoorthy3, Ayed Dera1, Majed Al Fayi1
1 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia
2 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha, Saudi Arabia; Department of Biochemistry, Faculty of Science, Alexandria University, Alexandria, Egypt
3 Department of Microbiology and Parasitology, Center for Stem Cell Research, College of Medicine, King Khalid University, Abha, KSA
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha
Source of Support: None, Conflict of Interest: None
Context: Rational screening of arylidene derivatives for biological activities has resulted in many lead molecules with anticancer properties with effective therapeutic window.
Aims: In the current study, FCX, an arylidene derivative, was screened for anticolon and prostate cancer activity.
Settings and Design: Prostate and colon cancer cell lines were used to check the FCX effect on proliferation, apoptosis, and mechanism of drug action.
Subjects and Methods: LNCaP, PC-3, HCT-8, and HT-29 cells were treated with various concentrations of the FCX. MTT assay was performed to check proliferation, propidium iodide and Hoechst dual staining for DNA fragmentation, and Annexin V binding assay for apoptosis, and cell cycle assay was done using flow cytometry. Functional androgen-mutated receptor cells were used mechanistic pathway elucidation.
Statistical Analysis Used: A minimum of three individual replicates at different time periods were taken as mean value. The data were expressed in mean ± standard deviation. Student's t-test and one-way ANOVA were used to assess the statistical difference between the groups.
Results: FCX inhibited proliferation of prostate cancer cell lines in a dose-dependent manner with more selectivity toward LNCaP cells. Nuclear fragmentation and dose-dependent increase in Annexin V-positive LNCaP cells revealed apoptosis. Cell cycle G2/M phase arrest along with sub-G0/G1 population augmented the antiproliferative observations. Addition of FCX in the presence of estradiol, testosterone, and dehydroepiandrosterone, LNCaP cells markedly caused a dose-dependent increase in cell proliferation indicating the compound activity to be facilitated through androgen receptor pathway.
Conclusions: Together with the results, it is evident that FCX has a wide therapeutic window in the in vitro inhibition of the prostate cancer cells mediated by hormone-dependent effects.