Ciprofloxacin and Levofloxacin as Potential Drugs in Genitourinary Cancer Treatment—The Effect of Dose–Response on 2D and 3D Cell Cultures

Introduction: Introducing new drugs for clinical application is a very difficult, long, drawn-out, and costly process, which is why drug repositioning is increasingly gaining in importance. The aim of this study was to analyze the cytotoxic properties of ciprofloxacin and levofloxacin on bladder and prostate cell lines in vitro. Methods: Bladder and prostate cancer cell lines together with their non-malignant counterparts were used in this study. In order to evaluate the cytotoxic effect of both drugs on tested cell lines, MTT assay, real-time cell growth analysis, apoptosis detection, cell cycle changes, molecular analysis, and 3D cultures were examined. Results: Both fluoroquinolones exhibited a toxic effect on all of the tested cell lines. In the case of non-malignant cell lines, the cytotoxic effect was weaker, which was especially pronounced in the bladder cell line. A comparison of both fluoroquinolones showed the advantage of ciprofloxacin (lower doses of drug caused a stronger cytotoxic effect). Both fluoroquinolones led to an increase in late apoptotic cells and an inhibition of cell cycle mainly in the S phase. Molecular analysis showed changes in BAX, BCL2, TP53, and CDKN1 expression in tested cell lines following incubation with ciprofloxacin and levofloxacin. The downregulation of topoisomerase II genes (TOP2A and TOP2B) was noticed. Three-dimensional (3D) cell culture analysis confirmed the higher cytotoxic effect of tested fluoroquinolone against cancer cell lines. Conclusions: Our results suggest that both ciprofloxacin and levofloxacin may have great potential, especially in the supportive therapy of bladder cancer treatment. Taking into account the low costs of such therapy, fluoroquinolones seem to be ideal candidates for repositioning into bladder cancer therapeutics.

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Differential radiosensitisation of bladder cancer cell lines by gemcitabine and its relationship to P53 status and cell cycle perturbations

European Urology Supplements ◽

10.1016/s1569-9056(02)80155-5 ◽

2002 ◽

Vol 1 (1) ◽

pp. 42

Author(s):

Vijay Sangar ◽

Richard Cowan ◽

Steve Roberts ◽

Geoff Margison ◽

Jolyon Hendry ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Bladder Cancer Cell ◽

P53 Status

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Evaluation of a novel irreversible pan-HER inhibitor in bladder cancer models.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.6_suppl.253 ◽

2013 ◽

Vol 31 (6_suppl) ◽

pp. 253-253

Author(s):

Petros Grivas ◽

Andreas Karatsinides ◽

Kathleen C. Day ◽

Priya Kunju ◽

Alyssa Paul ◽

...

Keyword(s):

Cell Cycle ◽

Bladder Cancer ◽

Cell Viability ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Bladder Cancer Cell ◽

Phase Iii ◽

Cytostatic Effect ◽

Cancer Models

253 Background: Human epidermal receptors (HER) are overexpressed and HER signaling is biologically relevant in bladder cancer and may mediate chemotherapy resistance. Dacomitinib is a novel, potent, irreversible pan-HER inhibitor with activity against several solid tumors, currently in a phase III clinical trial in NSCLC. We hypothesized that dacomitinib has antitumor activity in bladder cancer models. Methods: Expression level of EGFR and HER2 protein was measured semi-quantitatively in 8 bladder cancer cell lines. We treated UM-UC-3, UM-UC-6, UM-UC-9 cell lines with dacomitinib (1nM-10uM) for 24-72 hours, and measured cell viability, proliferation, apoptosis, and cell cycle effects. Correlations between dose and cell viability were measured by two-way ANOVA (GraphPad Prism 5.0). We injected age-matched male NOD/SCID mice SC with 1x106 UM-UC-6 and UM-UC-9 cells, respectively, generating xenografts. Mice were randomized and treated with dacomitinib, 6mg/kg p.o. daily, starting 1 day or 1 week after cell injection; controls were treated with vehicle. Mice were monitored daily, weighed weekly, sacrificed at 4 weeks and tumors weighed. Results: In vitro, significant cytostatic effect was noted with as low as 50nM in UM-UC6 cells and 100nM in UM-UC9 cells. UM-UC3 cells did not exhibit cytostatic effect even with 1000nM, corresponding to differential target protein (HER) expression. Dacomitinib (2uM) induced apoptosis (UM-UC-6), and G1 cell cycle arrest in both cell lines. These effects corresponded to dacomitinib-mediated inhibition of EGFR, ERK, AKT phosphorylation. In vivo, xenograft weights in both cell lines were significantly lower in dacomitinib-treated mice vs control (p<0.001), corresponding to pharmacodynamic effects (decreased E-cadherin, p-EGFR, p-ERK, mitotic count). Dacomitinib 6mg/kg p.o. daily resulted in significantly lower tumor weights vs lapatinib 50 mg/kg p.o. daily in UM-UC-9 xenograft model (p=0.0052). Conclusions: Dacomitinib demonstrated single-agent activity in bladder cancer cell lines and xenografts. Induction of apoptosis and G1 phase arrest are the suggested mechanisms for anti-tumor activity. Further investigation of this inhibitor in bladder cancer models is being pursued.

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Anticancer Activity of Water and Methanol Extracts of Hypericum scabrum L. on Different Cancer Cell Lines

Notulae Scientia Biologicae ◽

10.15835/nsb11410597 ◽

2019 ◽

Vol 11 (4) ◽

pp. 333-336

Author(s):

Gulsen GUCLU ◽

Ayca TAS ◽

Manhal TULIMAT ◽

Nuraniye ERUYGUR ◽

Yavuz SILIG

Keyword(s):

Cell Lines ◽

Cancer Cell ◽

Cytotoxic Effect ◽

Methanol Extract ◽

Water Extract ◽

Antiviral Effect ◽

Cancer Cell Lines ◽

Prostate Cell ◽

Methanol Extracts ◽

Hypericum Scabrum

Hypericum scabrum L. is an endemic medicinal plant with antimicrobial, anticancer and anti-inflammatory, antiviral effect. In this study, we aimed to investigate the cytotoxic effect of water and methanol extracts on different cancer cell lines such as osteosarcoma cancer, cervical cancer and prostate cancer. The data showed that the methanol extract had a highly effective cytotoxic effect on all three cell lines. Although water extract caused less cell loss than methanol extract, it was found that the cells were inhibited in all three cell lines. DU-145, which is the prostate cell line, was more effective in both extracts. As a result, the water and methanol extract of Hypericum scabrum L. have an anticancer effect on Saos-2, HeLa and DU-145 cells. There is a need for further and comprehensive studies by isolating the main active ingredient of this plant which is a candidate for drug of cancer in the future. Our study is expected to lead the studies in this direction.

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Induction of Apoptosis and Cell Cycle Blockade by Helichrysetin in A549 Human Lung Adenocarcinoma Cells

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/857257 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Yen Fong Ho ◽

Saiful Anuar Karsani ◽

Wai Kuan Yong ◽

Sri Nurestri Abd Malek

Keyword(s):

Cell Cycle ◽

Lung Adenocarcinoma ◽

Cell Lines ◽

Cancer Cell ◽

Cytotoxic Effect ◽

Molecular Mechanisms ◽

Human Lung ◽

Cancer Cell Lines ◽

Human Lung Adenocarcinoma ◽

Induction Of Apoptosis

Researchers are looking into the potential development of natural compounds for anticancer therapy. Previous studies have postulated the cytotoxic effect of helichrysetin towards different cancer cell lines. In this study, we investigated the cytotoxic effect of helichrysetin, a naturally occurring chalcone on four selected cancer cell lines, A549, MCF-7, Ca Ski, and HT-29, and further elucidated its biochemical and molecular mechanisms in human lung adenocarcinoma, A549. Helichrysetin showed the highest cytotoxic activity against Ca Ski followed by A549. Changes in the nuclear morphology of A549 cells such as chromatin condensation and nuclear fragmentation were observed in cells treated with helichrysetin. Further evidence of apoptosis includes the externalization of phosphatidylserine and the collapse of mitochondrial membrane potential which are both early signs of apoptosis. These signs of apoptosis are related to cell cycle blockade at the S checkpoint which suggests that the alteration of the cell cycle contributes to the induction of apoptosis in A549. These results suggest that helichrysetin has great potentials for development as an anticancer agent.

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