Analysis of the erythroid differentiation effect of flavonoid apigenin on K562 human chronic leukemia cells

Abstract

The erythroid differentiation-inducing effect of apigenin and its derivatives on human chronic myeloid leukemia K562 has been reported but the functional group in its structure responsible for the effect has not yet been elucidated. Here, we determined the moiety responsible for the erythroid differentiation induction effect of apigenin by using different flavonoids to represent the functional groups in its structure. In addition, we compared apigenin and apigetrin, a flavonoid similar in structure to apigenin except for the glycoside in its structure. Morphological changes as well as expressions of specific markers in K562 cells treated with apigenin were compared with those treated with apigetrin, flavone, 7-hydroxyflavone, chrysin, luteolin, or naringenin. The anti-proliferative and erythroid differentiation-inducing effect of apigenin and the five flavonoids were then investigated and their effects on the α, β, and γ globin genes expressions were compared using real-time PCR. Results of the comparison between apigenin and apigetrin revealed that the glycoside part of apigetrin does not have a role in the induction of cell differentiation. Based on glycophorin A expression, the potency of the other flavonoids for induction of differentiation, was: apigenin>chrysin>flavone/7-hydroxyflavone>luteolin/naringenin. Results of the analysis of the relationship between the structure and function of the flavonoids suggest that the apigenin-induced K562 cell differentiation was due to the 2-3 double bond and hydroxyl groups in its structure. This is the first study that identified the specific functional group in apigenin that impact the erythroid differentiation effect in K562 cells.

Health functionality of apigenin: A review

“…Leukaemia cell lines K562 human chronic leukaemia cells Apigenin induced erythrocyte differentiation in K562 human chronic leukaemia cells via 2-3 double bond and hydroxyl group in its moiety. [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.…”

Flavonoids Isolated from <i>Vitex grandifolia</i>, an Underutilized Vegetable, Exert Monoamine A & B Inhibitory and Anti-inflammatory Effects and Their Structure-activity Relationship

“…isoorientin (1), orientin (2); Wang et al 33 reported the hydroxylation pattern, its importance in C-3′-hydroxylation in the case of fisetin and 5-hydroxylation in the case of isoflavones gives significant effects for inducing cell delineation (apigenin vs. chrysin) especially ring B moiety; 34 (c) the position of the sugar moiety and glycosides on ring A gives better antiinflammatory activity than on rings B and C; Isoda et al gave an assessment that glycosides with significant hydrophilicity displayed lower anti-inflammatory activity, which may be due to lower hydrophobicity as well as steric interference, lessening membrane permeability. 35…”

Plant Flavone Apigenin: an Emerging Anticancer Agent

“…Apigenin-induced expressions of α, β, and γ globin genes increased the expression of glycosporin as a marker for differentiation. The hydroxyl groups are likely to render apigenin effective for inducing cell differentiation [188]. …”