Abstract
Kaempferol is a polyphenol found in a variety of plants. Kaempferol exerts antitumor properties by affecting proliferation and apoptosis of cancer cells. We investigated whether kaempferol and its glycoside derivatives—kaempferol 3-O-[(6-O-E-caffeoyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P2), kaempferol 3-O-[(6-O-E-p-coumaroyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P5) and kaempferol 3-O-[(6-O-E-feruloyl)-β-D-glucopyranosyl-(1→2)]-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (P7), isolated from aerial parts of Lens culinaris Medik.—affect the antitumor activity of etoposide in human promyelocytic leukemia (HL-60) cells. We analyzed the effect of kaempferol and its derivatives on cytotoxicity, DNA damage, apoptosis, cell cycle progression and free radicals induced by etoposide. We demonstrated that kaempferol increases the sensitivity of HL-60 cells to etoposide but does not affect apoptosis induced by this drug. Kaempferol also reduces the level of free radicals generated by etoposide. Unlike kaempferol, some of its derivatives reduce the apoptosis of HL-60 cells (P2 and P7) and increase the level of free radicals (P2 and P5) induced by etoposide. Our results indicate that kaempferol and its glycoside derivatives can modulate the activity of etoposide in HL-60 cells and affect its antitumor efficacy in this way. Kaempferol derivatives may have the opposite effect on the action of etoposide in HL-60 cells compared to kaempferol.
Highlights
Kaempferol [3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] (Fig. 1A)is a flavonoid with an anticancer potential that can be found in a variety of plants and plant-derived food products, such as lentils, tea, broccoli or apples [1,2,3,4]
Medik. on the anticancer activity of etoposide in HL-60 cells. This is the first study that focuses on the effect of kaempferol and its glycosides on etoposide activity such as cytotoxicity, induction of apoptosis and DNA damage, cell cycle arrest and production of free radicals
Our results indicate that kaempferol does not have an impact on the level of apoptosis induced by etoposide in HL-60 cells (Figure 6A)
Summary
We are looking for a compound which, on one hand, would enhance the effect of chemotherapeutic agents on cancer cells, and, on the other hand, protect normal cells. It has been demonstrated that kaempferol protected the vascular endothelium against doxorubicin-induced damage by regulating 14-3-3γ and ADMA/DDAHII/eNOS/NO pathways, inhibiting oxidative stress, and improving mitochondrial function [16]. Other polyphenols, such as curcumin [17]. Our earlier studies prompted us to the present examination of the effect of kaempferol and its glycoside derivatives (Figure 1) isolated from lentils on anticancer activity of etoposide in HL-60 cells. We tested the effect of kaempferol and its glycosides on DNA damage and cell cycle progression in HL-60 cells incubated with etoposide
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