Interaction of Candida albicans with genital mucosa: effect of sex hormones on adherence of yeasts in vitro

1988 ◽  
Vol 34 (3) ◽  
pp. 224-228 ◽  
Author(s):  
Aliza Kalo ◽  
Esther Segal

Findings from our previous studies revealed a correlation between the level of adherence in vitro of Candida albicans to human exfoliated vaginal epithelial cells (VEC) and the hormonal status of the cell donors. In the present study we investigated the effect of the sex hormones estradiol, estriol, progesterone, and testosterone on the binding of the yeasts to HeLa cell lines and VEC in vitro. Monolayers of HeLa cells were exposed to the hormones and yeasts under controlled conditions. The number of adherent yeasts per square millimetre of HeLa cell monolayers and the percentage of VEC with adherent yeasts was estimated by microscopic counts. The results showed that the tested sex hormones affected at various degrees the adhesion of yeasts to HeLa cells or VEC. Progesterone had the most marked effect, leading to a significant increase in the number of adherent yeasts to HeLa cells or in the percentage of adhesion of VEC. In addition, VEC were separated on Percoll gradients into the two cell types: superficial (S) and intermediate (I), cell types which appear physiologically under increased serum levels of estradiol or progesterone, respectively. Adhesion assays with the separated cell populations revealed an increased binding capacity of the I cells. The finding that progesterone increased the adherence of yeasts to genital mucosa and that VEC of the I type have a higher capacity to adhere the yeasts is compatible with our previous observation that increased numbers of I cells, appearing under high level of progesterone, are found in situations known to have predisposition to vaginal candidiasis. Thus, our data point to a possible involvement of the hormone progesterone in the adherence of C. albicans to genital epithelium.

2021 ◽  
Vol 22 (21) ◽  
pp. 11997
Author(s):  
Diana. K. Latypova ◽  
Stanislav V. Shmakov ◽  
Sofya A. Pechkovskaya ◽  
Alexander S. Filatov ◽  
Alexander V. Stepakov ◽  
...  

A series of heterocyclic compounds containing a spiro-fused pyrrolo[3,4-a]pyrrolizine and tryptanthrin framework have been synthesized and studied as potential antitumor agents. Cytotoxicity of products was screened against human erythroleukemia (K562) and human cervical carcinoma (HeLa) cell lines. Among the screened compounds. 4a, 4b and 5a were active against human erythroleukemia (K562) cell line, while 4a and 5a were active against cervical carcinoma (HeLa) cell line. In agreement with the DNA cytometry studies, the tested compounds have achieved significant cell-cycle perturbation with higher accumulation of cells in G2/M phase and induced apoptosis. Using confocal microscopy, we found that with 4a and 5a treatment of HeLa cells, actin filaments disappeared, and granular actin was distributed diffusely in the cytoplasm in 76–91% of cells. We discovered that HeLa cells after treatment with compounds 4a and 5a significantly reduced the number of cells with filopodium-like membrane protrusions (from 63 % in control cells to 29% after treatment) and a decrease in cell motility.


2019 ◽  
Vol 7 (4) ◽  
pp. 91-96
Author(s):  
Isra'a Al-sobhi ◽  
◽  
Rawan Al-Ghabban ◽  
Soad Shaker Ali ◽  
Jehan Al-Amri ◽  
...  

2017 ◽  
Vol 41 (7) ◽  
pp. 2543-2560 ◽  
Author(s):  
G. Kalaiarasi ◽  
Ruchi Jain ◽  
H. Puschman ◽  
S. Poorna Chandrika ◽  
K. Preethi ◽  
...  

Four new binuclear nickel(ii) metallates showed promising antiproliferative activity against MCF-7 and HeLa cell lines and were much less toxic against HaCaT.


2004 ◽  
Vol 48 (1) ◽  
pp. 161-167 ◽  
Author(s):  
Mahomed-Yunus S. Moosa ◽  
Jack D. Sobel ◽  
Hussain Elhalis ◽  
Wenjin Du ◽  
Robert A. Akins

ABSTRACT Fluconazole (FLZ) has emerged as a highly successful agent in the management of systemic infections of Candida. Cure rates for symptomatic candidiasis following single 150-mg FLZ dose therapy exceed 90%. In vitro, however, FLZ is fungistatic only in a narrow pH range and is not effective at vaginal pH, 4.2. This study evaluated the effect of FLZ on Candida albicans under in vitro conditions resembling the vaginal microenvironment, using vagina-simulative medium (VS). We found that FLZ was fungicidal for C. albicans in VS, but not in other media at the same pH, 4.2. In VS, FLZ was fungicidal at concentrations of ≥8 μg/ml and reduced viability by greater than 99.9%. Analysis of the components of VS indicated that 17 mM acetic acid, a concentration achieved in the vagina, was responsible for the synergistic, fungicidal effect. This effect was not seen at neutral pH. Other substrates were not effective substitutes for acetic acid; however, short-chained carboxylic acids, glyoxylate and malonate, were effective. Most strains of C. albicans that were resistant to FLZ under standard conditions were killed by FLZ plus acetate. Other species of Candida were also killed, except C. krusei and C. glabrata. This study shows that FLZ has fungicidal activity for Candida species under in vitro conditions that mimic the vaginal microenvironment. This raises the possibility that FLZ may also have fungicidal effects during treatment of vaginal candidiasis. Elucidating the mechanism by which FLZ and acetate interact may disclose vulnerable pathways that could be exploited in drug development.


2009 ◽  
Vol 53 (9) ◽  
pp. 3963-3971 ◽  
Author(s):  
Akihiro Kitamura ◽  
Saito Higuchi ◽  
Masato Hata ◽  
Katsuhiro Kawakami ◽  
Kumi Yoshida ◽  
...  

ABSTRACT β-1,6-Glucan is a fungus-specific cell wall component that is essential for the retention of many cell wall proteins. We recently reported the discovery of a small molecule inhibitor of β-1,6-glucan biosynthesis in yeasts. In the course of our study of its derivatives, we found a unique feature in their antifungal profile. D21-6076, one of these compounds, exhibited potent in vitro and in vivo antifungal activities against Candida glabrata. Interestingly, although it only weakly reduced the growth of Candida albicans in conventional media, it significantly prolonged the survival of mice infected by the pathogen. Biochemical evaluation of D21-6076 indicated that it inhibited β-1,6-glucan synthesis of C. albicans, leading the cell wall proteins, which play a critical role in its virulence, to be released from the cell. Correspondingly, adhesion of C. albicans cells to mammalian cells and their hyphal elongation were strongly reduced by the drug treatment. The results of the experiment using an in vitro model of vaginal candidiasis showed that D21-6076 strongly inhibited the invasion process of C. albicans without a significant reduction in its growth in the medium. These evidences suggested that D21-6076 probably exhibited in vivo efficacy against C. albicans by inhibiting its invasion process.


2008 ◽  
Vol 7 (3) ◽  
pp. 483-492 ◽  
Author(s):  
Yue Fu ◽  
Guanpingsheng Luo ◽  
Brad J. Spellberg ◽  
John E. Edwards ◽  
Ashraf S. Ibrahim

ABSTRACT We developed a conditional overexpression/suppression genetic strategy in Candida albicans to enable simultaneous testing of gain or loss of function in order to identify new virulence factors. The strategy involved insertion of a strong, tetracycline-regulated promoter in front of the gene of interest. To validate the strategy, a library of genes encoding glycosylphosphatidylinositol (GPI)-anchored surface proteins was screened for virulence phenotypes in vitro. During the screening, overexpression of IFF4 was found to increase the adherence of C. albicans to plastic and to human epithelial cells, but not endothelial cells. Consistent with the in vitro results, IFF4 overexpression modestly increased the tissue fungal burden during murine vaginal candidiasis. In addition to the in vitro screening tests, IFF4 overexpression was found to increase C. albicans susceptibility to neutrophil-mediated killing. Furthermore, IFF4 overexpression decreased the severity of hematogenously disseminated candidiasis in normal mice, but not in neutropenic mice, again consistent with the in vitro phenotype. Overexpression of 12 other GPI proteins did not affect normal GPI protein cell surface accumulation, demonstrating that the overexpression strategy did not affect the cell capacity for making such proteins. These data indicate that the same gene can increase or decrease candidal virulence in distinct models of infection, emphasizing the importance of studying virulence genes in different anatomical contexts. Finally, these data validate the use of a conditional overexpression/suppression genetic strategy to identify candidal virulence factors.


2021 ◽  
Vol 4 (3) ◽  
pp. 192-201
Author(s):  
Mosab Yahya Al-Nour ◽  
Ahmed H Arbab ◽  
Mohammad Khalid Parvez ◽  
Arwa Y Mohamed ◽  
Mohammed S Al-Dosari

This study aimed to investigate the anticancer activity of Haplophyllum tuberculatum(Forsk.) aerial parts ethanol extract and fractions and reveal the potential anticancer targets, binding modes, pharmacokinetics, and toxicity properties of its phytoconstituents. MTT assay was used to investigate the anticancer activity. TargetNet, ChemProt version 2.0, and CLC-Pred web servers were used for virtual screening, and Cresset Flare software was used for molecular docking with the 26 predicted targets. Moreover, pkCSM, swiss ADME, and eMolTox web servers were used to predict pharmacokinetics and safety. Ethanolic extracts of H. tuberculatum on HepG2 and HeLa cell lines showed promising activities with IC50 values 54.12 and 48.1 µg/mL, respectively. Further, ethyl acetate fraction showed the highest cytotoxicity on HepG2 and HeLa cell lines with IC50 values 41.7 and 52.31 µg/mL. Of 70 compounds screened virtually, polygamain, justicidin A, justicidin B, haplotubine, kusunokinin, and flindersine were predicted as safe anticancer drugs candidates. They showed the highest binding scores with targets involved in cell growth, proliferation, survival, migration, tumor suppression, induction of apoptosis, metastasis, and drug resistance. Our findings revealed the potency of H. tuberculatum as a source of anticancer candidates that further studies should support.


2019 ◽  
Vol 12 (10) ◽  
pp. 1616-1623
Author(s):  
Annise Proboningrat ◽  
Amaq Fadholly ◽  
Regina Purnama Dewi Iskandar ◽  
Agung Budianto Achmad ◽  
Fedik Abdul Rantam ◽  
...  

Background and Aim: Cervical cancer accounts for the fourth as a cause of death from cancer in women worldwide, with more than 85% of events and deaths occurring in developing countries. The main problems of chemotherapy are the lack of selectivity and drug resistance. This study aimed to investigate the signal transduction of chitosan-based Pinus merkusii bark extract nanoparticles (Nano-PMBE) as an anticancer on HeLa cell line. Materials and Methods: Nano-PMBE was prepared based on the ionic gelation method. Its anticancer activities in HeLa cells were investigated through cytotoxicity test, cell cycle, and apoptosis analysis. The expression of p53 and caspase-9 was also observed. Results: The results showed that Nano-PMBE has a size of 394.3 nm. Meanwhile, the Nano-PMBE was cytotoxic to HeLa cells ( IC50 of 384.10 μg/ml), caused G0/G1 phase arrest and cell apoptosis in HeLa cells. Besides, the expression of p53 and caspase-9 has increased. Conclusion: The results showed a notable anticancer effect of Nano-PMBE by arresting the cell cycle and inducing apoptosis in HeLa cells, suggesting that it might have therapeutic potential for cervical cancer. Further research is needed to find out more about the anticancer mechanism of Nano-PMBE in HeLa cells to in vivo and clinical studies.


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