Increased anti-tumour effects of doxorubicin and zoledronic acid in prostate cancer cells in vitro: supporting the benefits of combination therapy

2009 ◽  
Vol 65 (5) ◽  
pp. 969-978 ◽  
Author(s):  
Rhys D. Clyburn ◽  
Penny Reid ◽  
Catherine A. Evans ◽  
Diane V. Lefley ◽  
Ingunn Holen
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Prostate Cancer Cells

Novel combination therapy of prostate cancer cells with arsenic trioxide and flutamide: An in-vitro study

2022 ◽  
Vol 74 ◽  
pp. 101684
Author(s):  
Akram Mirzaei ◽  
Mohammad Reza Akbari ◽  
Seyed Saeed Tamehri Zadeh ◽  
Fatemeh Khatami ◽  
Rahil Mashhadi ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Combination Therapy ◽  
Cancer Cells ◽  
Arsenic Trioxide ◽  
In Vitro Study ◽  
Vitro Study ◽  
Prostate Cancer Cells

Additive/synergistic antitumoral effects on prostate cancer cells in vitro following treatment with a combination of docetaxel and zoledronic acid

2005 ◽  
Vol 44 (6) ◽  
pp. 644-650 ◽  
Author(s):  
Anders Ullén ◽  
Lena Lennartsson ◽  
Ulrika Harmenberg ◽  
Marie Hjelm-Eriksson ◽  
Karl Mikael Kälkner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Prostate Cancer Cells

scholarly journals Zoledronic acid influences growth, migration and invasive activity of prostate cancer cells in vitro

2012 ◽  
Vol 15 (3) ◽  
pp. 250-255 ◽  
Author(s):  
J Mani ◽  
S Vallo ◽  
K Barth ◽  
J Makarević ◽  
E Juengel ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Prostate Cancer Cells

scholarly journals Zoledronic Acid and Leuprorelin Acetate, Alone or in Combination, Similarly Reduce Proliferation and Migration of Prostate Cancer Cells In Vitro

2014 ◽  
Vol 1 ◽  
pp. 1-7 ◽  
Author(s):  
Barbara Mognetti ◽  
Giuseppe La Montagna ◽  
Maria Giulia Perrelli ◽  
Silvia Marino ◽  
Pasquale Pagliaro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Cancer Cells ◽  
Prostate Cancer Cells ◽  
Leuprorelin Acetate ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals Zoledronic Acid Enhances the Chemotherapeutic Efficiency of 5-fluorouracil or Flutamide in Prostate Cancer Cells with Modulation of miR-382 and miR-18a Expression

2021 ◽  
Vol 72 (2) ◽  
pp. 102-118
Author(s):  
Amr M. Yehia ◽  
Mahmoud G. Eldeib ◽  
Ahmed M. Mohamadin ◽  
Mohammed M. El-Zahab
Keyword(s):  
Prostate Cancer ◽  
Zoledronic Acid ◽  
Combination Therapy ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Caspase 3 ◽  
Health Concern ◽  
Prostate Cancer Cells ◽  
Chemotherapeutic Efficacy ◽  
Du145 Cells

Owing to a lack of appropriate therapeutic regimens, prostate cancer (PC) is a global health concern with a high incidence and mortality rate in elderly men. Combination treatment seems to have the highest clinical benefit and avoids unwanted side effects. The current study focused on the chemotherapeutic efficacy of Zoledronic acid (ZA) in combination with 5-fluorouracil (5-FU) or Flutamide on prostate cancer cells, as well as its effect on apoptosis. The MTT assay was used to determine the cytotoxic effect of Zoledronic acid (ZA), 5-FU, and flutamide on PC-3 and DU-145 cells, as well as the combined therapy of ZA with 5-FU or flutamide. Additionally, immunofluorescence staining analysis was used to assess changes in Bcl-2 and p53 expression. Furthermore, the western blotting method was extensively used to evaluate Bax, caspase 3, and cyclin D1. Furthermore, quantitative real-time polymerase chain reaction (qRT-PCR) was applied to determine the relative expression of miRNA-382 (miR-382) and miRNA-18a (miR-18a). Instead of (13.47, 8.23, and 9.42 μM) for PC-3 or (38.77, 17.6, and 8.47 μM) for DU145 cells, the combination therapy improved cytotoxicity with doses approximately half of IC50 (6.74, 4.12, and 7.07 μM) in PC-3 and (19.38, 8.8, and 6.33 μM) in DU145 cells for ZA, 5-FU, and flutamide, respectively. When compared to a single therapy, the combination therapy significantly up-regulated the pro-apoptotic Bax, cleaved caspase 3 and p53 levels while down-regulated the cyclin D1 and Bcl-2 expression. In addition, the combination therapy was linked to changes in miR-382 and miR-18a expression. Our findings suggest that combining ZA with 5-FU or flutamide improves chemotherapeutic efficacy against prostate cancer cells, at least in part by encouraging apoptosis and modulating miRNA expression, especially miR-382 and miR-18a.

scholarly journals Acetyl-L-Carnitine downregulates invasion (CXCR4/CXCL12, MMP-9) and angiogenesis (VEGF, CXCL8) pathways in prostate cancer cells: rationale for prevention and interception strategies

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Denisa Baci ◽  
Antonino Bruno ◽  
Caterina Cascini ◽  
Matteo Gallazzi ◽  
Lorenzo Mortara ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Growth ◽  
Cancer Cells ◽  
Dietary Supplements ◽  
Cell Lines ◽  
Angiogenic Factors ◽  
Migration And Invasion ◽  
Prostate Cancer Cells

Abstract Background Prostate cancer (PCa) is a leading cause of cancer-related death in males worldwide. Exacerbated inflammation and angiogenesis have been largely demonstrated to contribute to PCa progression. Diverse naturally occurring compounds and dietary supplements are endowed with anti-oxidant, anti-inflammatory and anti-angiogenic activities, representing valid compounds to target the aberrant cytokine/chemokine production governing PCa progression and angiogenesis, in a chemopreventive setting. Using mass spectrometry analysis on serum samples of prostate cancer patients, we have previously found higher levels of carnitines in non-cancer individuals, suggesting a protective role. Here we investigated the ability of Acetyl-L-carnitine (ALCAR) to interfere with key functional properties of prostate cancer progression and angiogenesis in vitro and in vivo and identified target molecules modulated by ALCAR. Methods The chemopreventive/angiopreventive activities ALCAR were investigated in vitro on four different prostate cancer (PCa) cell lines (PC-3, DU-145, LNCaP, 22Rv1) and a benign prostatic hyperplasia (BPH) cell line. The effects of ALCAR on the induction of apoptosis and cell cycle arrest were investigated by flow cytometry (FC). Functional analysis of cell adhesion, migration and invasion (Boyden chambers) were performed. ALCAR modulation of surface antigen receptor (chemokines) and intracellular cytokine production was assessed by FC. The release of pro-angiogenic factors was detected by a multiplex immunoassay. The effects of ALCAR on PCa cell growth in vivo was investigated using tumour xenografts. Results We found that ALCAR reduces cell proliferation, induces apoptosis, hinders the production of pro inflammatory cytokines (TNF-α and IFN-γ) and of chemokines CCL2, CXCL12 and receptor CXCR4 involved in the chemotactic axis and impairs the adhesion, migration and invasion capabilities of PCa and BPH cells in vitro. ALCAR exerts angiopreventive activities on PCa by reducing production/release of pro angiogenic factors (VEGF, CXCL8, CCL2, angiogenin) and metalloprotease MMP-9. Exposure of endothelial cells to conditioned media from PCa cells, pre-treated with ALCAR, inhibited the expression of CXCR4, CXCR1, CXCR2 and CCR2 compared to those from untreated cells. Oral administration (drinking water) of ALCAR to mice xenografted with two different PCa cell lines, resulted in reduced tumour cell growth in vivo. Conclusions Our results highlight the capability of ALCAR to down-modulate growth, adhesion, migration and invasion of prostate cancer cells, by reducing the production of several crucial chemokines, cytokines and MMP9. ALCAR is a widely diffused dietary supplements and our findings provide a rational for studying ALCAR as a possible molecule for chemoprevention approaches in subjects at high risk to develop prostate cancer. We propose ALCAR as a new possible “repurposed agent’ for cancer prevention and interception, similar to aspirin, metformin or beta-blockers.

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