# Effects of Thyme, Cumin, and Sumac Extracts on Apoptosis and Paraptosis in Hepatocellular Carcinoma: Synergistic, Antagonistic, or Additive Properties

## TL;DR

This study examines how thyme, cumin, and sumac extracts affect cell death in liver cancer cells and identifies their combined effects as synergistic, additive, or antagonistic.

## Contribution

The study reveals distinct mechanisms and combined effects of thyme, cumin, and sumac extracts on apoptosis and paraptosis in hepatocellular carcinoma.

## Key findings

- Sumac and thyme extracts showed an additive effect on cell death in HepG2 cells.
- Thyme and cumin extracts exhibited an antagonistic effect, while sumac and cumin showed a synergistic effect.
- The extracts induced apoptosis via different protein pathways, suggesting potential for cancer treatment.

## Abstract

This study evaluated the effect of single, double, and triple combined doses of sumac, thyme, and cumin extracts on apoptosis and paraptosis in the HepG2 cell line. The effect of thyme and cumin extracts was higher in proteins (mTOR, caspase‐8, caspase‐9, Bax and bcl‐2) other than caspase‐3 protein. The expression of caspase‐3 protein was higher in the sumac extract‐treated groups. The expression levels of GRP78/Bip and DDIT3/Chop proteins, which are indicators of paraptosis, did not exert a significant difference between the extracts. Even though their protein expression is different, according to MTT results, sumac and thyme extracts showed an additive effect, thyme and cumin extracts showed an antagonistic effect, sumac and cumin extracts showed a synergistic effect, and sumac, thyme, and cumin extracts showed a synergistic effect. Sumac, thyme, and cumin extracts induced cell death by causing apoptosis in HepG2 cells, and they may have a supportive impact on the treatment of hepatocellular carcinoma.

While sumac induced apoptosis via caspase‐3 expression, thyme and cumin caused apoptosis by altering the expression of caspase‐8, caspase‐9, bax, and bcl‐2 proteins. In cell cytotoxicity, sumac and thyme showed an additive effect, thyme and cumin showed an antagonistic effect, and sumac and cumin showed a synergistic effect.