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The anticarcinogen activity of β-arbutin on MCF-7 cells: Stimulation of apoptosis through estrogen receptor-α signal pathway, inflammation and genotoxicity

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Abstract

Arbutin is one of the active ingredients employed in cosmetics as a skin whitening agent. In the present study, the possible effects of arbutin on breast cancer were determined with human breast adenocarcinoma (MCF-7) cells. α and β-arbutin cytotoxicity levels in MCF-7 cells were determined with the MTT method. At low (1–10 mM) doses, α-arbutin appears to be more toxic than β-arbutin. At higher (5–200 mM) and LD50 doses beta arbutin toxicity appears to be higher than alpha arbutin. Thus, the study was continued with β -arbutin. The effects of low and high doses of β-arbutin was determined on oxidative stress, genotoxicity, inflammation, apoptosis, proliferation, endoplasmic reticulum stress and estrogen receptor-α in MCF-7 cells. The results demonstrated that the β-arbutin doses administered to MCF-7 cells did not affect oxidative and endoplasmic reticulum stress in the experimental groups. However, it was found that administration of LD50 dose β-arbutin induced inflammation in these cells via proinflammatory cytokine levels (TNF-α, IFN-γ and IL-1β). It was observed that LD10 and LD50 doses of β-arbutin increased genotoxicity in MCF-7 cells. The gene expression analysis conducted with RT-PCR device and immunocytochemical analysis revealed that β-arbutin at LD50 dose induced apoptosis in MCF-7 cells via p53 and Caspase 3. Furthermore, it was determined that all β-arbutin doses inhibited estrogen receptor-α in MCF-7 cells. Considering that arbutin increased the activation of apoptotic Caspase 3 through p53, which was stimulated by genotoxic and inflammatory effects at LD50 dose in MCF-7 cells. Determination of this mechanism behind these effects of β-arbutin may contribute to the development of a new perspective in treatment.

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Funding

This work was supported by Scientific Research Projects Committee (Project Number: 16.FEN.BIL.15) by the Rectorate of Afyon Kocatepe University, Afyonkarahisar, Turkey.

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Correspondence to Ömer Hazman.

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Hazman, Ö., Sarıova, A., Bozkurt, M.F. et al. The anticarcinogen activity of β-arbutin on MCF-7 cells: Stimulation of apoptosis through estrogen receptor-α signal pathway, inflammation and genotoxicity. Mol Cell Biochem 476, 349–360 (2021). https://doi.org/10.1007/s11010-020-03911-7

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