Therapeutic Potential of Apigenin, a Plant Flavonoid, for Imatinib-Sensitive and Resistant Chronic Myeloid Leukemia Cells

Abstract

Despite the presence of many therapeutic regimens like imatinib and other tyrosine kinase inhibitors, the development of resistance, intolerance, and side effects makes chronic myeloid leukemia (CML) therapy challenging. Thus, there is a need to discover novel drugs for CML patients. In this study, we attempted to assess apigenin, a common plant dietary flavonoid, in terms of its cytotoxic, apoptotic, and cytostatic effects on imatinib-sensitive and resistant Philadelphia-positive CML cells. We analyzed apigenin's effects on cell proliferation, apoptosis, caspase-3 activity, loss of mitochondrial membrane potential, and cell cycle progression in K562 and K562/IMA3 cells. Furthermore, we described genes and Results of our study revealed that apigenin has cytotoxic and apoptotic effects on both cell types. We also displayed that apigenin induced G2/M arrest in K562 cells while arresting K562/IMA3 cells in S phase especially at the highest apigenin concentration. The expression analysis identified a set of genes that were regulated by apigenin in K652 and K562/IMA3 cells. Association of modulated genes with biological functional groups identified several networks affected by apigenin including cell survival, proliferation, cell death, cell cycle, and cell signalling pathways.

The Flavonoid Apigenin Ameliorates Cisplatin-Induced Nephrotoxicity through Reduction of p53 Activation and Promotion of PI3K/Akt Pathway in Human Renal Proximal Tubular Epithelial Cells

“…Interestingly, apigenin itself inhibited cell growth because of its ability to induce cell cycle arrest at S and G2/M phases. In line with this, apigenin has been previously reported to inhibit cell proliferation and induces cell cycle arrest in various cell types [ 30 – 33 ].…”

Apigenin in cancer therapy: anti-cancer effects and mechanisms of action

“…And in an oral squamous cell carcinoma cell line SCC-25, apigenin treatment caused cell cycle arrest at both G0/G1 and G2/M checkpoints, associated with decreased expression of cyclin D1 and E, and inactivation of CDK1 [ 33 ]. Interestingly, Solmaz et al reported that apigenin exposure induced G2/M arrest in imatinib-sensitive K562 cells while arresting imatinib-resistant K562/IMA3 cells in S phase especially at 100 μM apigenin [ 34 ]. Taken together, those data suggest that apigenin possibly modulates cell cycle progression in a dose-dependent and/or cell line specific manner.…”

Health functionality of apigenin: A review

“…[301] K562 and K562/IMA3 cell lines The study concluded that apigenin inhibits cell proliferation and induces apoptosis by upregulating the activity of caspase-3 and arresting the cells in G2/M phase of cell cycle repectively. [302] Myeloma cell lines U266 and RPMI 8226 Apigenin was found to kill MM cells by targeting the trinity of CK2-Cdc37-Hsp90. By depleting these kinases, apigenin suppresses both constitutive and inducible activation of STAT3, ERK, AKT and NF-кB.…”