(+)-Medioresinol leads to intracellular ROS accumulation and mitochondria-mediated apoptotic cell death in Candida albicans

Biochimie ◽  
2012 ◽  
Vol 94 (8) ◽  
pp. 1784-1793 ◽  
Author(s):  
Ji Hong Hwang ◽  
In-sok Hwang ◽  
Qing-He Liu ◽  
Eun-Rhan Woo ◽  
Dong Gun Lee
FEBS Journal ◽  
2012 ◽  
Vol 279 (7) ◽  
pp. 1327-1338 ◽  
Author(s):  
In-sok Hwang ◽  
Juneyoung Lee ◽  
Ji Hong Hwang ◽  
Keuk-Jun Kim ◽  
Dong Gun Lee

2011 ◽  
Vol 173 (4) ◽  
pp. 207-218 ◽  
Author(s):  
In-sok Hwang ◽  
Juneyoung Lee ◽  
Hong-Guang Jin ◽  
Eun-Rhan Woo ◽  
Dong Gun Lee

2015 ◽  
Vol 59 (4) ◽  
pp. 2153-2168 ◽  
Author(s):  
B. N. Singh ◽  
D. K. Upreti ◽  
B. R. Singh ◽  
G. Pandey ◽  
S. Verma ◽  
...  

ABSTRACTQuorum sensing (QS) regulates group behaviors ofCandida albicanssuch as biofilm, hyphal growth, and virulence factors. The sesquiterpene alcohol farnesol, a QS molecule produced byC. albicans, is known to regulate the expression of virulence weapons of this fungus. Fluconazole (FCZ) is a broad-spectrum antifungal drug that is used for the treatment ofC. albicansinfections. While FCZ can be cytotoxic at high concentrations, our results show that at much lower concentrations, quercetin (QC), a dietary flavonoid isolated from an edible lichen (Usnealongissima), can be implemented as a sensitizing agent for FCZ-resistantC. albicansNBC099, enhancing the efficacy of FCZ. QC enhanced FCZ-mediated cell killing of NBC099 and also induced cell death. These experiments indicated that the combined application of both drugs was FCZ dose dependent rather than QC dose dependent. In addition, we found that QC strongly suppressed the production of virulence weapons—biofilm formation, hyphal development, phospholipase, proteinase, esterase, and hemolytic activity. Treatment with QC also increased FCZ-mediated cell death in NBC099 biofilms. Interestingly, we also found that QC enhances the anticandidal activity of FCZ by inducing apoptotic cell death. We have also established that this sensitization is reliant on the farnesol response generated by QC. Molecular docking studies also support this conclusion and suggest that QC can form hydrogen bonds with Gln969, Thr1105, Ser1108, Arg1109, Asn1110, and Gly1061 in the ATP binding pocket of adenylate cyclase. Thus, this QS-mediated combined sensitizer (QC)-anticandidal agent (FCZ) strategy may be a novel way to enhance the efficacy of FCZ-based therapy ofC. albicansinfections.


Oncotarget ◽  
2017 ◽  
Vol 8 (69) ◽  
pp. 114050-114064 ◽  
Author(s):  
Wan Gi Hong ◽  
Ju Yeon Kim ◽  
Jeong Hyun Cho ◽  
Sang-Gu Hwang ◽  
Jie-Young Song ◽  
...  

2021 ◽  
Vol 17 (1) ◽  
pp. 171-180
Author(s):  
Petchi Iyappan ◽  

The immature lymphoid cells with chromosomal structural and numerical abnormalities cause the acute lymphoblastic leukemia (ALL). This hematologic disorder constitutes about 25% of cancer prognosis among children and adolescents. D-Carvone, a monocyclic monoterpene obtained from the essential oils extracted from plants is reported to possess the various biological activities. The present study was aimed to investigate the anticancer potential of D-Carvone against the human leukemic Molt-4 cells. The cytotoxicity of DCarvone was analyzed by MTT assay. The level of lipid peroxidation and antioxidants were determined. The intracellular ROS, MMP and apoptosis were demonstrated by fluorescent staining techniques. The MTT assay revealed that the D-Carvone treatment suppressed the viability of Molt-4 cells and the IC50 was determined at 20 μM/ml. The D-Carvone treatment was increased the oxidative stress and reduced the level of antioxidants in the Molt-4 cell lines. The increased intracellular ROS, apoptotic cell death, and diminished MMP was noted in the D-Carvone treatment. In the Molt-4 cells, D-carvone induced the apoptosis in a time and dose dependent manner by the activation of caspases-8, -9 and -3. Thus, data provide insights for the clinical application of D-Carvone in the treatment of blood cancer Molt-4 cells. Our study suggests the therapeutic potential D-Carvone for the treatment of leukemia in future.


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