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

Kayacan S., Yilancioglu K., Akdemir A. S. , DAĞISTANLI F., Melikoglu G. , Ozturk M.

ANTICANCER RESEARCH, vol.41, no.3, pp.1271-1282, 2021 (Journal Indexed in SCI) identifier identifier

  • Publication Type: Article / Article
  • Volume: 41 Issue: 3
  • Publication Date: 2021
  • Doi Number: 10.21873/anticanres.14884
  • Title of Journal : ANTICANCER RESEARCH
  • Page Numbers: pp.1271-1282


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.