| Autor: |
Ben-Eltriki M; Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada; Therapeutics Initiative, Department of Anesthesiology, Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada., Deb S; Department of Pharmaceutical Sciences, College of Pharmacy, Larkin University, 18301 N. Miami Avenue, Miami, FL, 33169, USA. Electronic address: sdeb@alumni.ubc.ca., Guns EST; Vancouver Prostate Centre at Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada. Electronic address: emmabluetube@gmail.com. |
| Jazyk: |
angličtina |
| Zdroj: |
The Journal of steroid biochemistry and molecular biology [J Steroid Biochem Mol Biol] 2021 May; Vol. 209, pp. 105828. Date of Electronic Publication: 2021 Jan 22. |
| DOI: |
10.1016/j.jsbmb.2021.105828 |
| Abstrakt: |
1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3 , commonly known as calcitriol), the most active metabolite of vitamin D 3 , and ginsenoside Rh2 can regulate cellular differentiation and proliferation proteins. The purpose of the present study was to assess the effect of 1,25(OH) 2 D 3 on the anticancer activities of Rh2 in human prostate cancer cells such as androgen-dependent LNCaP and androgen-independent C4-2 in vitro. The effects of treatment with 1,25(OH) 2 D 3 or Rh2, either alone or in combination, on prostate cancer cells were evaluated through tetrazolium-based cell viability assay, BrdU cell proliferation rate estimation assay, and Western blot protein expression analyses of nuclear receptors (androgen receptor and vitamin D receptors) and apoptotic proteins (Bcl-2, Bax, and Caspase 3). The Combination Indices (CI) and Dose Reduction Indices (DRI) of 1,25(OH) 2 D 3 and Rh2 were calculated to determine synergistic anticancer activity using Calcusyn software (Biosoft, Cambridge, UK). The cell viability assay data indicate that Rh2 treatment alone inhibited cell viability in a concentration-dependent manner and the addition of 10 nM 1,25(OH) 2 D 3 to Rh2 significantly enhanced its ability to reduce cell viability up to 80 % in both the cell lines. Similarly, addition of 10 nM 1,25(OH) 2 D 3 to Rh2 significantly lowered its IC 50 values for cell proliferation from the range of 32-65 μM to 14-8 μM in LNCaP and C4-2 cells. In addition, protein expression analyses indicated that the combined treatment with Rh2 and 1,25(OH) 2 D 3 led to greater downregulation of androgen receptor expression compared to single agent exposure. Similarly, the presence of 1,25(OH) 2 D 3 synergistically increased the pro-apoptotic actions of Rh2 in both the cell lines. Overall, 1,25(OH) 2 D 3 augments the Rh2-mediated anticancer effects through stimulating apoptosis and reduced cell proliferation which suggests that synergism of this combination may lead to potential lower need of the active vitamin D 3 and limited toxicity from it.
(Copyright © 2021 Elsevier Ltd. All rights reserved.) |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
Full Text from ScienceDirect