scholarly journals The Effect of Fatty Acids on Ciprofloxacin Cytotoxic Activity in Prostate Cancer Cell Lines. Does Lipid Component Enhance Anticancer Ciprofloxacin Potential?

Cancers ◽  
2022 ◽  
Vol 14 (2) ◽  
pp. 409
Author(s):  
Alicja Chrzanowska ◽  
Wioletta Olejarz ◽  
Grażyna Kubiak-Tomaszewska ◽  
Andrzej K. Ciechanowicz ◽  
Marta Struga

Purpose: To assess cytotoxic effect of ciprofloxacin conjugates with fatty acids on prostate cancer cells (LNCaP and DU-145) with different hormone sensitivity, based on previous promising results from the PC3 cells. Methods: Cytotoxicity were estimated using MTT and LDH tests, whereas its mechanisms were estimated by apoptosis and IL-6 assays. The intensity of proteins involved in lipid metabolism was determined using ML-CS assay. Results: The hormone insensitive DU-145 cells were more vulnerable than the hormone sensitive LNCaP cells. The IC50 values for oleic (4), elaidic (5) and docosahexaenoic acid (8) conjugates were 20.2 µM, 17.8 µM and 16.5 µM, respectively, in DU-145 cells, whereas in LNCaP cells IC50 exceeded 20 µM. The strong conjugate cytotoxicity was confirmed in the LDH test, the highest (70.8%) for compound (5) and 64.2% for compound (8) in DU-145 cells. This effect was weaker for LNCaP cells (around 60%). The cytotoxic effect of unconjugated ciprofloxacin and fatty acids was weaker. The early apoptosis was predominant in LNCaP while in DU-145 cells both early and late apoptosis was induced. The tested conjugates decreased IL-6 release in both cancer cell lines by almost 50%. Proteomic analysis indicated influence of the ciprofloxacin conjugates on lipid metabolic proteins in prostatic cancer. Conclusion: Our findings suggested the cytotoxic potential of ciprofloxacin conjugates with reduction in proteins involved in prostate cancer progress.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21135-21135
Author(s):  
M. Toledo Lobo ◽  
M. Arenas Jiménez ◽  
L. Huertas Martínez ◽  
S. Sacristán lópez ◽  
A. Moyano Jato ◽  
...  

21135 Background: The mechanism through wich zoledronic acid exerts its activity is poorly understood. Low density lipoprotein receptor (LDLR) and scavenger receptor class B type 1 (SRBI) overproduction is an important mechanism in cancer cells for obtaining more essential fatty acids and cell growth. The effects of in vitro zoledronate treatment on the lipid metabolism of prostate cancer cell lines were studied. Methods: Three prostatic cancer cell lines, androgen insensitive PC3, androgen dependent low-passage (LP) LNCaP and androgen independent high-passage (HP) LNCaP cells were studied. Cells were plated either in RPMI with 5% foetal calf serum and lipoprotein depleted serum (LPDS) and were treated with zoledronate at different concentrations. The lipid transporters profile was analyzed by western blotting for LDLR and SRB1. Results: The same LDLR bands profile was observed in all cell lines, 160 and 105 kDa. The basal levels of LDLR were higher in the PC3 cells. Zoledronate therapy induced LDLR expression in all cell lines but PC3 were less sensitive to this effect. Cells cultured with LPDS showed an enhanced expression of LDLR and PC3 cells were less sensitive to this effect. HP LNCaP cells were the most affected by lipoprotein deprivation however this effect diminished 72 hours after treatment. The bands profile for SRBI consisted of a 65 kDa predominant band and a 40 kDa band in both LP/HP LNCaP cells. In PC3 cells main band was located in 65 kDa and accessory band in 30kDa. The basal levels of the 65kDa band were higher in HP than in LP LNCaP or PC3 cells and zoledronate therapy caused a dose- dependent induction in HP LNCaP and dose-dependent reduction in PC3 cells, LP LNCaP cells were resistant to the treatment. LPDS induced SRBI levels in all cell lines inverting the effect caused by zoledronate in HP LNCaP cells in complete culture medium and at high doses (100μM) a complete inhibition of SRBI protein was found. Low molecular weight bands changed in the same way as the 65 kDa band. Conclusions: LDL-R and SRBI have been isolated in prostate cancer cell lines. Based on previous cell growth studies, the lipid transporters profile might be significantly involved in the resistance to zoledronate therapy. Lipoprotein regulation pathways should be considered in the therapy of metastatic prostate cancer. No significant financial relationships to disclose.


1992 ◽  
Vol 68 (06) ◽  
pp. 662-666 ◽  
Author(s):  
W Hollas ◽  
N Hoosein ◽  
L W K Chung ◽  
A Mazar ◽  
J Henkin ◽  
...  

SummaryWe previously reported that extracellular matrix invasion by the prostate cancer cell lines, PC-3 and DU-145 was contingent on endogenous urokinase being bound to a specific cell surface receptor. The present study was undertaken to characterize the expression of both urokinase and its receptor in the non-invasive LNCaP and the invasive PC-3 and DU-145 prostate cells. Northern blotting indicated that the invasive PC-3 cells, which secreted 10 times more urokinase (680 ng/ml per 106 cells per 48 h) than DU-145 cells (63 ng/ml per 106 cells per 48 h), had the most abundant transcript for the plasminogen activator. This, at least, partly reflected a 3 fold amplification of the urokinase gene in the PC-3 cells. In contrast, urokinase-specific transcript could not be detected in the non-invasive LNCaP cells previously characterized as being negative for urokinase protein. Southern blotting indicated that this was not a consequence of deletion of the urokinase gene. Crosslinking of radiolabelled aminoterminal fragment of urokinase to the cell surface indicated the presence of a 51 kDa receptor in extracts of the invasive PC-3 and DU-145 cells but not in extracts of the non-invasive LNCaP cells. The amount of binding protein correlated well with binding capacities calculated by Scatchard analysis. In contrast, the steady state level of urokinase receptor transcript was a poor predictor of receptor display. PC-3 cells, which were equipped with 25,000 receptors per cell had 2.5 fold more steady state transcript than DU-145 cells which displayed 93,000 binding sites per cell.


2017 ◽  
Vol 24 (1) ◽  
pp. 17-30 ◽  
Author(s):  
K M Biernacka ◽  
R A Persad ◽  
A Bahl ◽  
D Gillatt ◽  
J M P Holly ◽  
...  

The incidence of many common cancers varies between different populations and appears to be affected by a Western lifestyle. Highly proliferative malignant cells require sufficient levels of nutrients for their anabolic activity. Therefore, targeting genes and pathways involved in metabolic pathways could yield future therapeutics. A common pathway implicated in energetic and nutritional requirements of a cell is the LKB1/AMPK pathway. Metformin is a widely studied anti-diabetic drug, which improves glycaemia in patients with type 2 diabetes by targeting this pathway. We investigated the effect of metformin on prostate cancer cell lines and evaluated its mechanism of action using DU145, LNCaP, PC3 and VCaP prostate cancer cell lines. Trypan blue dye-exclusion assay was used to assess levels of cell death. Western immunoblotting was used to determine the abundance of proteins. Insulin-like growth factor-binding protein-2 (IGFBP-2) and AMPK genes were silenced using siRNA. Effects on cell morphology were visualised using microscopy. IGFBP-2 gene expression was assessed using real-time RT-PCR. With DU145 and LNCaP cells metformin alone induced cell death, but this was reduced in hyperglycaemic conditions. Hyperglycaemia also reduced the sensitivity to Docetaxel, but this was countered by co-treatment with metformin. LKB1 was required for the activation of AMPK but was not essential to mediate the induction of cell death. An alternative pathway by which metformin exerted its action was through downregulation of IGFBP-2 in DU145 and LNCaP cells, independently of AMPK. This finding could have important implications in relation to therapeutic strategies in prostate cancer patients presenting with diabetes.


2021 ◽  
Author(s):  
Karolina Sienkiewicz ◽  
Chunsong Yang ◽  
Bryce M. Paschal ◽  
Aakrosh Ratan

The lymph node metastasis-derived LNCaP, the bone metastasis-derived PC3 (skull), and VCaP (vertebral) cell lines are widely used preclinical models of human prostate cancer (CaP) and have been described in >19,000 publications. Here, we report on short-read whole-genome sequencing and genomic analyses of LNCaP, VCaP, and PC3 cells stably transduced with WT AR (PC3-AR) . LNCaP cells are composed of multiple subpopulations, which results in non-integral copy number states and a high mutational load when the data is analyzed in bulk. All three cell lines contain pathogenic mutations and homozygous deletions in genes involved in DNA mismatch repair, along with deleterious mutations in cell-cycle, Wnt signaling, and other cellular processes. Furthermore, LNCaP cells contain a missense mutation in a well-known CaP hotspot of TP53, whereas both PC3-AR and VCaP have truncating mutations in TP53 and do not express p53 protein. In addition, we detect the signatures of chromothripsis of the q arms of chromosome 5 in both PC3-AR and VCaP cells, strengthening the association of TP53 inactivation with chromothripsis reported in other systems. Our work provides a resource for genetic, genomic, and biological studies employing these commonly-used prostate cancer cell lines.


2020 ◽  
Vol 58 (1) ◽  
pp. 12
Author(s):  
Tran Khac Vu

The paper presents a simple synthesis of new quinazolinone derivatives 13a-i. Synthesized derivatives were tested for their cytotoxic effect against three cancer cell lines including SKLU-1, MCF-7 and HepG-2. The bioassay result showed that only compound 13e exhibited significant cytotoxic effect against cancer cell lines tested with IC50 values of 9.48, 20.39 and 18.04 µg/ mL, respectively.


Author(s):  
Fatemeh Akbarian ◽  
Farid Dadkhah ◽  
Arezoo Campbel ◽  
Farrokh Asadi ◽  
Ghasem Ahangari

Background: Dopamine receptor (DR) gene family play an essential role in the regulation of interleukin-6 (IL-6) production. Our prior analysis of human prostate biopsy samples demonstrated the increased expression of IL-6 and a down regulating trend for dopamine receptor gene family. Objective: The objective was to investigate the expression of dopamine receptors, their catabolizing enzyme and IL-6 in prostate cancer cell lines and assess pharmacological effect of dopamine receptor modulators as a novel class of drugs repurposed for treatment of prostate cancer. Methods: The therapeutic effect of dopamine, DR agonists, and DR antagonist were examined using LNCaP and PC3 cell lines.CellviabilityandproliferationwereassessedbyMTTassayandproliferatingcellnuclearantigenexpressionanalysis, respectively. Furthermore, bax/bcl2 ratio, immunofluorescence assay and flow cytometric assay were performed for apoptosis analysis. RT-q PCR analysis was used to characterize relative expression of dopamine-related genes, catabolic enzyme catechol-o-methyl-transferase (COMT) and IL-6 before and after treatment to assess the therapeutic effects of drugs. Results: LNCaP cells express DRD1, DRD2, DRD5 and COMT genes and PC3 cells only express IL-6 gene. In-vitro, dopamine receptor agonists reduced cell viability of LNCaP and PC3 cells. In contrast, dopamine and dopamine receptor antagonist significantly increased tumor growth in PC3 cells. Conclusion: Our results offer novel suggestion for a pathogenic role of dopamine receptor signaling in prostate cancer adenocarcinoma and indicates that modulators of DR-IL-6 pathway, including FDA-approved drug bromocriptine, might be utilized as novel drug repurposing strategy.


2013 ◽  
Vol 3 ◽  
Author(s):  
Wouter Hendrickx ◽  
Julie Decock ◽  
Francis Mulholland ◽  
Yongping Bao ◽  
Susan Fairweather-Tait

2015 ◽  
Vol 23 (4) ◽  
pp. 203-8 ◽  
Author(s):  
Susi Endrini ◽  
Asmah Rahmat ◽  
Patimah Ismail ◽  
Y.H. Taufiq-Yap

Background: This study aimed to analyze the cytotoxicity effect of γ-sitosterol isolated from “Kejibeling” (Strobilanthes crispus), a medicinal plant, on several cancer cell lines. The mechanisms of the effects were studied through the expression of cancer-caused gene, c-myc and apoptotic pathways.Methods: This in vitro study was done using human colon cancer cell lines (Caco-2), liver cancer cell lines (HepG2), hormone-dependent breast cancer cell lines (MCF-7) and the normal liver cell lines (Chang Liver). The cytotoxic effect was measured through MTT assay and the potential cytotoxic value was calculated by determining the toxic concentration which may kill up to 50% of the total cell used (IC50). Meanwhile, the cytotoxic mechanism was studied by determining the effect of adding γ-sitosterol to the c-myc gene expression by reverse transciptase-polymerase chain reaction (RT-PCR). The effect of γ-sitosterol through apoptotic pathway was studied by using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay.Results: γ-sitosterol was cytotoxic against Caco-2, HepG2, and MCF-7 with IC50-values of 8.3, 21.8, and 28.8 μg/mL, respectively. There were no IC50-values obtained from this compound against Chang Liver cell line. This compound induced apotosis on Caco-2 and HepG2 cell lines and suppressed the c-myc genes expression in both cells.Conclusion: γ-sitosterol was cytotoxic against colon and liver cancer cell lines and the effect was mediated by down-regulation of c-myc expression and induction of the apoptotic pathways.


2018 ◽  
Vol 40 (2) ◽  
pp. 145-152
Author(s):  
Vu Thi Nguyet ◽  
Nguyen Tien Dat ◽  
Le Mai Huong ◽  
Tran Thi Hong Ha ◽  
Nguyen Hong Chuyen ◽  
...  

This paper reports the cytotoxic effect on several cancer cell lines of the stem extracts and of some isolated compounds from Ehretia asperula. All the extracts exhibited cytotoxic effects on at least one cancer cell line. The n-hexane extract showed potent cytotoxic activity on Hep-G2, MCF-7 and HeLa cell lines with IC50 values of 28.3 g/ml, 14.42 g/ml and 18.59 g/ml, respectively, while the methanolic, ethyl acetate and water extracts exhibited toxicity towards MCF-7 cells with IC50 values of 16.45 g/ml, 13.4 g/ml and 39.78 g/ml, respectively. 06 compounds have been isolated from the ethyl acetate fraction of Ehretia asperula stem. Methyl caffeate has a strong cytotoxicity against Hep-G2, HeLa and MCF-7 cancer cell lines with IC50 values of 2.83 g/ml, 3.38 g/ml and 4.4 g/ml, respectively. Oresbiusin B was active against Hep-G2 with IC50 value of 9.89 g/ml. The other compounds including coniferaldehyde, 9′-methoxydehydrodiconiferyl alcohol and vanillic acid did not have any cytotoxic effect on the tested cancer cell lines. So, the obtained results have suggested possibility of using the potential Ehretia asperula extracts as health food for preventing and curing cancer diseases. Keywords: Ehretia asperula, methyl caffeate, oresbiusin B, Cancer cell lines. Citation: Vu Thi Nguyet, Nguyen Tien Đat, Le Mai Huong, Tran Thi Hong Ha, Nguyen Hong Chuyen, Nguyen Thi Hang4, Đang Đinh Kim, 2018. Evaluating cytotoxic effect of the extracted compounds from ehretia asperula zoll. & mor stem on several cancer cell lines.Tap chi Sinh hoc, 40(2): 145153. https://doi.org/10.15625/0866-7160/v40n2.12955. *Corresponding author: [email protected]


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