Published April 1, 2021 | Version v.1
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Cytotoxic activities of Hypericum perforatum L. extracts against 2D and 3D cancer cell models.

  • 1. Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia "VINČA" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Alasa 12-14, Belgrade, Serbia
  • 2. Department of Medical Biology, Faculty of Medicine, Ondokuz Mayıs University, Samsun, Turkey
  • 3. Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia
  • 4. Department of Biochemistry, Faculty of Pharmacy, Sivas Cumhuriyet University, Sivas, Turkey
  • 5. Department of Medical Biochemistry, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey
  • 6. Department of Experimental Oncology, Institute for Oncology and Radiology of Serbia, Belgrade, Serbia
  • 7. Department of Natural Sciences in Pharmacy, Faculty of Pharmacy, University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  • 8. Department of Laboratory and Veterinary Health, Ulubey Vocational Higher School, Ordu University, Ordu, Turkey
  • 9. Institute of Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia; "VINČA" Institute of Nuclear Sciences, National Institute of the Republic of Serbia, University of Belgrade, Mike Alasa 12-14, Belgrade, Serbia

Description

Six extracts were obtained from plant species Hypericum perforatum L., collected at Samsun in Turkey. The aim of this study was to examine the mechanisms of the anticancer activity of these extracts. Methanol, ethyl-acetate and hexane were used as a solvents for extraction from both branch-body part of the plant (extracts 1, 2 and 3) and from plant flowers (extracts 4, 5 and 6). The cytotoxic effects of the extracts were determined against 2D and 3D cancer cell models. Cell cycle changes of treated HeLa cells were analyzed by flow cytometry. Measurements of gene and microRNA expression levels in treated HeLa cells were done by quantitative real time PCR. Five examined extracts (2–6) exerted selective concentration-dependent cytotoxic effects on HeLa, K562, and A549 cancer cells, while the extract 1 exhibited very weak cytotoxicity. The extract 6 showed the highest intensity of cytotoxic activity. All tested extracts (2–6) demonstrated the ability to induce apoptosis in HeLa cells through activation of caspase-3. These extracts remarkably decreased gene expression levels of MMP2MMP9TIMP3, and VEGFA in HeLa cells. Flower extracts might have stronger effects on miR128/193a-5p/335 level changes than branch-body extracts. Hypericum perforatum extracts exerted weaker cytotoxic effects on 3D HeLa spheroids when compared with their effects on 2D monolayer HeLa cells. Taken together, results of our research may suggest the promising anticancer properties of the Hypericum perforatum extracts.

Notes

Funding The authors are grateful to the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant No. 51-03-9/2021-14/200043) and Scientific Research Projects Unit of Ordu University (Project A-1823) for the financial support.

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0920-9069 (ISSN)