Dutasteride Synergistically Enhances 5-Fluorouracil Antiproliferative Effect on Prostate Cancer Cells
Zahraa Abdulhasan Jihad, Majid Kadhim Abbas, Kaiser N. MadlumAbstract
Background:
Prostate cancer is a complicated illness that affects millions of men worldwide, primarily in high human development index nations. Patients with localized illness who are at low-to-moderate risk of recurrence have a 99% overall survival rate for 10 years if the cancer is discovered and treated early. Treatments of prostate cancer include active surveillance, radical prostatectomy, androgen deprivation, and others. Testosterone and dihydrotestosterone are the main androgens that are associated with disease pathogenesis. The irreversible conversion of testosterone to dihydrotestosterone is catalyzed by 5-alpha reductase enzyme. Therefore, in the current study, we will evaluate antiproliferative, apoptotic, anti-inflammatory, and antioxidant effects of dutasteride, which is targeted both types (I and II) of 5-alpha reductase enzymes combined with 5-fluorouracil on androgen-sensitive prostate cancer cell line LNCap.
Materials and Methods:
Lymph node carcinoma of the prostate (LNCap) cells were incubated with different concentrations of dutasteride combined with 5FU then antiproliferative, apoptotic, anti-inflammatory, and antioxidant effects were assessed after 48 h using MTT [3-(4,5 dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] assay, caspase 3 ELISA kit, tumor necrosis factor (TNF)-alpha enzyme-linked immunoassay (ELISA) kit, and total antioxidant capacity ELISA kit, respectively.
Results:
Combination of dutasteride with 5FU showed decreasing effects on cell viability and TNF-alpha with no effects on total antioxidant capacity and caspase 3.
Conclusion:
Effects of the combination of dutasteride with 5FU gives synergistic effects on proliferation and inflammation properties with no effects on apoptosis and oxidative stress.