Different Cytotoxic Effects of Caper from Different Geographical Regions May Be Related to Changes in Mitochondrial Sirt3

Document Type: Original paper

Authors

1 Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Department of Pharmacology and Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Student Research Committee, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

2 Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Department of Toxicology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran.

3 Cellular and Molecular Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

4 Department of Pharmacology and Toxicology, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

5 Department of Pharmacognosy, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

6 Demepartment of Pharmacognosy, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran.

Abstract

Background and objectives: Beside its nutritional role, caper (Capparis spinosa) has long been used as an analgesic, anti-inflammatory, anti-diabetic and anti-cancer remedy. In the present study, we tested whether this plant can make effective changes in Sirt3 and mitochondrial function in colorectal carcinoma cell line since mitochondrial dysfunction has long been implicated in both cancer and diabetes and benefit confers by caper in these diseases might be due to mitochondrial alterations. Methods: Total flavonoids and phenolics were assayed using colorimetric tests. Cytotoxicity of a phenolic-flavonoid rich extract of caper collected from two different geographical regions (south and west) were mechanistically studied in HT-29 cell line. Activity of an essential mitochondrial enzyme, Sirt3 has also been evaluated along with other parameters. IC50 of extracts were determined by MTT cytotoxicity assay, cell death and mitochondrial membrane potential were evaluated via flow cytometric analysis. Also, at IC50 concentrations, Sirt3 activity was determined fluorimetrically. Results: The results showed that caper induced significant cytotoxicity in HT-29 cells followed by mitochondrial membrane potential collapse, ROS overproduction, Sirt3 activity alteration and cell death. Conclusions: The above-mentioned cytotoxic parameters were inversely proportional to the phenolic and flavonoid contents of the extract showing that other mechanisms beyond their antioxidant capacities may contribute to their anti-cancer effects. In other term, these results suggest that antioxidant capacity may not directly contribute to the anticancer property.

Keywords


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