Synergistic Effect of Apigenin and Curcumin on Apoptosis, Paraptosis and Autophagy-related Cell Death in HeLa Cells
Sera Kayacan1, Kaan Yilancioglu2, Ayse Seda Akdemir1
1Department of Medical Biology, Cerrahpasa Medical Faculty, Istanbul University-Cerrahpasa, Istanbul, Turkey.
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.
Insights
Apigenin and curcumin synergistically enhance anti-tumor effects in HeLa cells by modulating apoptosis, autophagy, and paraptosis. This combination shows promise as a potential therapeutic strategy for cervical cancers.
Area of Science:
- Cell biology
- Molecular oncology
- Pharmacology
Background:
- Apoptosis and autophagy are key cell death pathways.
- Their cross-talk influences cancer progression.
- Paraptosis, an ER stress-mediated cell death, is also relevant.
Purpose of the Study:
- Investigate synergistic effects of apigenin and curcumin.
- Analyze their impact on apoptosis-autophagy cross-talk.
- Examine their role in paraptosis induction.
Main Methods:
- MTT assay for cell viability.
- Bliss independence model for synergy.
- qRT-PCR for gene expression analysis.
- Immunostaining for ER stress markers.
Main Results:
- Combined apigenin and curcumin significantly increased cell death gene expression (1.29- to 27.6-fold).
- Demonstrated synergistic anti-tumor activity through apoptosis-autophagy cross-talk and paraptosis.
- Observed GRP78 downregulation and cytoplasmic vacuolization, indicating ER stress.
Conclusions:
- Apigenin and curcumin combination exhibits synergistic anti-tumor effects.
- This combination effectively targets apoptosis, autophagy, and paraptosis.
- Represents a promising therapeutic approach for cervical cancers.
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