Anti-Proliferative and Apoptotic Effects of Aqueous Extract of Ziziphus Jujube in Human Thyroid Carcinoma Cell Lines (C643)

Background: Ziziphus jujuba, which is known as “Annab” or “Onnab” in Iran, is an effective compound against some cancer cell lines. The present study aimed to investigate the anti-mutagenic and anticancer effects of the aqueous extract of Z. jujuba on C643 human thyroid carcinoma cells. Methods: C643 cells were cultured in (Roswell Park memorial institute) RPMI 1640 medium (Sigma) supplemented with 10% fetal bovine serum (FBS), penicillin-streptomycin, and L-glutamine. After incubating the cultures at 37oC with 5% CO2, MTT assay was used to determine the inhibitory effect of Z. jujuba on cell proliferation. Cell cycle progression was monitored by sub-G1 apoptosis assay using flow cytometry. Finally, anti-mutagenicity properties of the extract were evaluated using a standard reverse mutation assay (Ames test), which was performed with a histidine auxotroph strain of Salmonella typhimurium (TA100) and exposure to a carcinogenic substance (sodium azide). Results: The aqueous extract of Z. jujuba inhibited the growth of C643 cells in a concentration range of 0.5 - 2 mg/mL and exhibited cytotoxic effects on C643 cells in a concentration-dependent manner (IC50: 1.671 mg/mL). The mechanism of action was the induction of apoptosis in the cells. The results of Ames test indicated a significant difference in the anti-mutagenic effects of Z. jujuba aqueous extract and controls (distilled water and sodium azide) (1.671 mg/mL) (P < 0.01). In addition, the herbal extract prevented reverted mutations and the hindrance percent was 87.97%. Conclusions: According to the results, the aqueous extract of Z. jujuba fruit exerted anti-proliferative and apoptotic effects on C643 thyroid carcinoma cell lines and may be potentially useful as an anticancer agent.