Zataria multiflora extract enhances imatinib-induced cytotoxicity in chronic myeloid leukemia and multiple myeloma cells.

BACKGROUND

Zataria multiflora (ZM) is a medicinal plant with widespread antitumor effects. Tyrosine kinase inhibitors (TKIs) are considered the mainstay treatment in blood cancers; however, eventual resistance to TKIs poses a significant challenge in this area. The present study aimed to assess the synergistic effects of ZM extract (ZME) along with imatinib, a TKI, against K-562 and U-266 leukemic cell lines.

METHODS

Cell viability was evaluated using the MTT assay, and apoptosis assessment was also conducted through Annexin-V/PI staining. Additionally, Real-Time PCR was used to assess the expression levels of BCR-ABL, P-TEN, c-MYC, Bax, and Bcl-2 genes. Molecular docking was carried out as an in-silico technique for both BCL-2 and ABL proteins.

RESULTS

The results showed that both ZME and imatinib promoted apoptosis in K562 and U266 cells, with combination treatment significantly enhancing apoptotic cell death (e.g., 18.4% apoptosis in K562 cells with ZME + imatinib vs. 8.5% untreated; 46.9% in U266 cells vs. 11.6% untreated, P < 0.05). Combined treatment with imatinib and ZME upregulated the expression of Bax (5-fold in K562, 3-fold in U266) and P-TEN (2-fold in K562, 2.8-fold in U266) genes and downregulated the expression of Bcl-2 (0.3-fold in K562, 0.3-fold in U266), BCR-ABL (0.5-fold in K562), and c-MYC (0.4-fold in K562, 0.2-fold in U266) genes (P < 0.05). Molecular docking showed strong binding affinities between ZME constituents (carvacrol and thymol) and BCL-2 and ABL proteins.

CONCLUSIONS

ZME shows potential as a complementary agent in vitro, warranting further investigation.