Polyphenolic Flavonoid Compound Quercetin Effects in the Treatment of Acute Myeloid Leukemia and Myelodysplastic Syndromes

Abstract

Flavonoids are ubiquitous groups of polyphenolic compounds present in most natural products and plants. These substances have been shown to have promising chemopreventive and chemotherapeutic properties with multiple target interactions and multiple pathway regulations against various human cancers. Polyphenolic flavonoid compounds can block the initiation or reverse the promotion stage of multistep carcinogenesis. Quercetin is one of the most abundant flavonoids found in fruits and vegetables and has been shown to have multiple properties capable of reducing cell growth in cancer cells. Acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) therapy remains a challenge for hematologists worldwide, and the outcomes for patients with both disorders continue to be poor. This scenario indicates the increasing demand for innovative drugs and rational combinative therapies. Herein, we discuss the multitarget effects of the flavonoid quercetin, a naturally occurring flavonol, on AML and MDS.

Keywords: anti-proliferative effect; apoptosis; autophagy; epigenetic modifications; hematological disorders; polyphenolic compounds; quercetin.

Figure 1

Structure of the major classes of flavonoids.

Figure 2

Structure of quercetin. Quercetin contains the basic structure of flavonoids: diphenylpropane (C6–C3–C6) with hydroxyl groups attached to the rings. The official nomenclature according to IUPAC is 2-(3,4-dihydroxyphenyl)-3,5,7-trihydroxy-4H-chromen-4-one. Other names include 5,7,3′,4′-flavon-3-ol, sophoretin, meletin, quercetine, xanthaurine, quercetol, quercitin, quertine, and flavin meletin. Chemical formula: C₁₅H₁₀O₇.

Figure 3

Quercetin biosynthesis.

Figure 4

Antioxidative mechanism of quercetin. Quercetin is oxidized into oxidation products (QQ: ortho-quinone) and reacts with glutathione (GSH) to form 6-glutathionyl quercetin (6-GSQ) and 8-GSQ.

Figure 5

Multitarget effects of quercetin on acute myeloid leukemia and myelodysplastic syndrome.