Abstract
Malic acid (MA) has been commonly used in cosmetic products, but the safety reports in skin are sparse. To investigate the biological effects of MA in human skin keratinocytes, we investigated the potential cytotoxicity and apoptotic effects of MA in human keratinocyte cell lines (HaCaT). The data showed that MA induced apoptosis based on the observations of DAPI staining, DNA fragmentation, and sub-G1 phase in HaCaT cells and normal human epidermal keratinocytes (NHEKs). Flow cytometric assays also showed that MA increased the production of mitochondrial superoxide (mito-SOX) but decreased the mitochondrial membrane potential. Analysis of bioenergetics function with the XF 24 analyzer Seahorse extracellular flux analyzer demonstrated that oxygen consumption rate (OCR) was significantly decreased whereas extracellular acidification rate (ECAR) was increased in MA-treated keratinocytes. The occurrence of apoptosis was proved by the increased expressions of FasL, Fas, Bax, Bid, caspases-3, -8, -9, cytochrome c, and the declined expressions of Bcl-2, PARP. MA also induced endoplasmic reticulum stress associated protein expression such as GRP78, GADD153, and ATF6α. We demonstrated that MA had anti-proliferative effect in HaCaT cell through the inhibition of cell cycle progression at G0/G1, and the induction of programmed cell death through endoplasmic reticulum stress- and mitochondria-dependent pathways.
Highlights
Malic acid (MA), a sort of alpha-hydroxy acids (AHAs) found in fruits and many vegetables, has been commonly used in cosmetics and chemical peeling agents [1,2,3,4]
MA increased the expression of Fas-L, Fas, and caspase-8 and (Figure 6B). These findings show that MA induces apoptosis via the caspase- and mitochondrial-dependent pathway in HaCaT cells
We have reported that glycolic acid induced programmed cell death in HaCaT cells and human leukemia cell line HL-60 [8,18]
Summary
Malic acid (MA), a sort of alpha-hydroxy acids (AHAs) found in fruits and many vegetables, has been commonly used in cosmetics and chemical peeling agents [1,2,3,4]. Malic acid is used for light-damaged or dry skin, and acne [3]. Over 50 cosmetic formulations across a range of products have contained. Malic acid may induce skin and ocular irritation [4] and the biological and molecular effects of malic acid in human keratinocytes are still uncertain. We investigated the potential cytotoxicity and apoptotic effects of malic acid in human keratinocyte cell lines (HaCaT) and normal human epidermal keratinocytes (NHEKs)
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