Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions

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Marija Smiljkovic
Danijela Stanisavljevic
Dejan Stojkovic
Isidora Petrovic
Jelena Marjanovic Vicentic
Jelena Popovic
Simona Golic Grdadolnik
Dejan Markovic
Snežana Sankovic-Babice
Jasmina Glamoclija
Milena Stevanovic
Marina Sokovic


Bioactive potential of apigenin derivative apigenin-7-O-glucoside related to its antifungal activity on Candida spp. and cytotoxic effect on colon cancer cells was studied and compared with bioactive potential of apigenin. Antifungal activity was tested on 14 different isolates of Candida spp. using membrane permeability assay, measuring inhibition of reactive oxidative species and inhibition of CYP51 C. albicans enzyme. Cytotoxic potential of apigenin-7-O-glucoside was tested on colon cancer HCT116 cells by measuring cell viability, apoptosis rate and apoptosis- and colon cancer-related gene expression. Obtained results indicated considerable antifungal activity of apigenin-7-O-glucoside towards all Candida isolates. Breakdown of C. albicans plasma membrane was achieved upon treatment with apigenin-7-O-glucoside for shorter period of time then with apigenin. Reduction of intra- and extracellular reactive oxidative species was achieved with minimum inhibitory concentrations of both compounds, suggesting that reactive oxidative species inhibition could be a mechanism of antifungal action. None of the compounds exhibited binding affinity to C. albicans CYP51 protein. Besides, apigenin-7-O-glucoside was more effective compared to apigenin in reduction of cell's viability and induction of cell death of HCT116 cells. Treatment with both compounds resulted in chromatin condensation, apoptotic bodies formation and apoptotic genes expression in HCT116 cells, but the apigenin-7-O-glucoside required a lower concentration to achieve the same effect. Compounds apigenin-7-O-glucoside and apigenin displayed prominent antifungal potential and cytotoxic effect on HCT116 cells. However, our results showed that apigenin-7-O-glucoside has more potent activity compared to apigenin in all assays that we used.

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Smiljkovic, M., Stanisavljevic, D., Stojkovic, D., Petrovic, I., Marjanovic Vicentic, J., Popovic, J., Golic Grdadolnik, S., Markovic, D., Sankovic-Babice, S., Glamoclija, J., Stevanovic, M., & Sokovic, M. (2017). Apigenin-7-O-glucoside versus apigenin: Insight into the modes of anticandidal and cytotoxic actions. EXCLI Journal, 16, 795-807. https://doi.org/10.17179/excli2017-300
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