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Research ArticleExperimental Studies

Synergistic Effect of Apigenin and Curcumin on Apoptosis, Paraptosis and Autophagy-related Cell Death in HeLa Cells

SERA KAYACAN, KAAN YILANCIOGLU, AYSE SEDA AKDEMIR, FATMA KAYA-DAGISTANLI, GULAY MELIKOGLU and MELEK OZTURK
Anticancer Research March 2021, 41 (3) 1271-1282; DOI: https://doi.org/10.21873/anticanres.14884
SERA KAYACAN
1Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey;
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KAAN YILANCIOGLU
2Department of Chemistry–Biology Engineering, Faculty of Engineering and Natural Sciences, Uskudar University, Istanbul, Turkey;
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AYSE SEDA AKDEMIR
1Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey;
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FATMA KAYA-DAGISTANLI
1Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey;
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GULAY MELIKOGLU
3Department of Pharmacognosy, Pharmacy Faculty, Istanbul University, Istanbul, Turkey
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MELEK OZTURK
1Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey;
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  • For correspondence: mozturk@istanbul.edu.tr
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Abstract

Background/Aim: We aimed to investigate the synergistic effects of apigenin and curcumin on the cross-talk between apoptosis and autophagic cell death, as well as on paraptosis in HeLa cells. Materials and Methods: Cell viability was measured using the MTT assay. Synergistic effects were measured using the Bliss independence model. qRT-PCR was used to study the expression of genes related to apoptosis, autophagic cell death, and cross-talk. GRP78/BiP immunostaining was used to identify endoplasmic reticulum (ER) stress. Results: Treatment with a combination of apigenin and curcumin increased the expression levels of genes related to cell death in HeLa cells 1.29- to 27.6-fold. The combination of curcumin and apigenin showed a synergistic anti-tumor effect via cross-talk between processes leading to apoptosis and autophagic cell death, as well as ER stress-associated paraptosis. GRP78 expression was down-regulated, and massive cytoplasmic vacuolization was observed in HeLa cells. Conclusion: The combination of curcumin and apigenin is an effective potential therapeutic for cervical cancers.

Key Words:
  • Curcumin
  • apigenin
  • synergy
  • autophagic cell death
  • apoptosis
  • paraptosis
  • GRP78
  • HeLa cell
  • Received January 20, 2021.
  • Revision received January 30, 2021.
  • Accepted February 1, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (3)
Anticancer Research
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March 2021
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Synergistic Effect of Apigenin and Curcumin on Apoptosis, Paraptosis and Autophagy-related Cell Death in HeLa Cells
SERA KAYACAN, KAAN YILANCIOGLU, AYSE SEDA AKDEMIR, FATMA KAYA-DAGISTANLI, GULAY MELIKOGLU, MELEK OZTURK
Anticancer Research Mar 2021, 41 (3) 1271-1282; DOI: 10.21873/anticanres.14884

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Synergistic Effect of Apigenin and Curcumin on Apoptosis, Paraptosis and Autophagy-related Cell Death in HeLa Cells
SERA KAYACAN, KAAN YILANCIOGLU, AYSE SEDA AKDEMIR, FATMA KAYA-DAGISTANLI, GULAY MELIKOGLU, MELEK OZTURK
Anticancer Research Mar 2021, 41 (3) 1271-1282; DOI: 10.21873/anticanres.14884
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Keywords

  • Curcumin
  • apigenin
  • synergy
  • autophagic cell death
  • apoptosis
  • paraptosis
  • GRP78
  • HeLa cell
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