The Effects of Resveratrol-Rich Extracts of <i>Vitis vinifera</i> Pruning Waste on HeLa, MCF-7 and MRC-5 Cells: Apoptosis, Autophagia and Necrosis Interplay
Aleksandra Jovanović Galović,
Nataša Jovanović Lješković,
Senka Vidović,
Jelena Vladić,
Nikola Jojić,
Milan Ilić,
Tatjana Srdić Rajić,
Vesna Kojić,
Dimitar Jakimov
Affiliations
Aleksandra Jovanović Galović
Faculty of Pharmacy Novi Sad, University of Business Academy, Trg Mladenaca 5, 21000 Novi Sad, Serbia
Nataša Jovanović Lješković
Faculty of Pharmacy Novi Sad, University of Business Academy, Trg Mladenaca 5, 21000 Novi Sad, Serbia
Senka Vidović
Faculty of Technology, Department of Biotechnology and Pharmaceutical Engineering, University of Novi Sad, Bulevar Cara Lazara 1, 21000 Novi Sad, Serbia
Jelena Vladić
Faculty of Technology, Department of Biotechnology and Pharmaceutical Engineering, University of Novi Sad, Bulevar Cara Lazara 1, 21000 Novi Sad, Serbia
Nikola Jojić
Faculty of Pharmacy Novi Sad, University of Business Academy, Trg Mladenaca 5, 21000 Novi Sad, Serbia
Milan Ilić
Faculty of Pharmacy Novi Sad, University of Business Academy, Trg Mladenaca 5, 21000 Novi Sad, Serbia
Tatjana Srdić Rajić
Institute for Oncology and Radiology of Serbia, Department of Experimental Oncology, Pasterova 14, 11000 Belgrade, Serbia
Vesna Kojić
Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put doktora Goldmana 4, 21204 Sremska Kamenica, Serbia
Dimitar Jakimov
Oncology Institute of Vojvodina, Faculty of Medicine, University of Novi Sad, Put doktora Goldmana 4, 21204 Sremska Kamenica, Serbia
Resveratrol is a well-studied plant-derived molecule in cancer biology, with a plethora of documented in vitro effects. However, its low bioavailability and toxicity risk hamper its wider use. In this study, vine shoots after pruning were used as a source of resveratrol (RSV). The activity of subcritical water extract (SWE) and dry extract (DE) is examined on three cell lines: HeLa, MCF-7 and MRC-5. The cytotoxic effect is assessed by the MTT test and EB/AO staining, levels of apoptosis are determined by Annexin V assay, autophagia by ULK-1 expression using Western blot and NF-kB activation by p65 ELISA. Our results show that both resveratrol-rich extracts (DE, SWE) have a preferential cytotoxic effect on malignant cell lines (HeLa, MCF-7), and low cytotoxicity on non-malignant cells in culture (MRC-5). Further experiments indicate that the investigated malignant cells undergo different cell death pathways. MCF-7 cells died preferentially by apoptosis, while the HeLa cells died most likely by necrosis (possibly ferroptosis). Protective autophagia is diminished upon treatment with DE in both HeLa and MCF-7 cells, while SWE does not influence the level of autophagia. The extracts are effective even at low concentrations (below IC50) in the activation of NF-kB (p65 translocation).
