Fundamental Toxicological Sciences
Online ISSN : 2189-115X
ISSN-L : 2189-115X
Original Article
Aristolochic acid C displays cytotoxic effect and remarkable enhancing effect on the all-trans retinoic acid-induced superoxide-generating ability in U937 cells
Hidehiko KikuchiKaori HarataHarishkumar MadhyasthaHitomi MimuroFutoshi Kuribayashi
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2024 Volume 11 Issue 4 Pages 197-204

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Abstract

Aristolochic acids (AAs) with strong bio-toxicity are the natural compounds that consist in Aristolochiaceae plants. There are the governing health issues regarding toxicities of AAs although Aristolochiaceae plants have been used as herbal medicines. For example, AAs are known as significant risk factors for nephropathy, urological cancer, liver cancer and so on. However, the understandings about the molecular mechanisms of toxicity of each AA derivative have been still poor and insufficiently studied. In this study, we investigated the effects of four AA derivatives (AA-A, AA-B, AA-C and AA-D) on the viability and the all-trans retinoic acid (ATRA)-induced superoxide anion (O2-)-generating ability of human leukemia U937 cells. AA-A and AA-C remarkably reduced cell viability when co-treated with ATRA while AA-B and AA-D had little effect on viability of U937 cells. On the other hand, only AA-C among the four AAs dramatically up-regulated the ATRA-induced O2--generating ability. Quantitative RT-PCR and immunoblotting analyses showed that AA-C significantly enhances the ATRA-induced O2--generating ability via up-regulating gene expression levels of gp91-phox, which is an essential factor for the O2--generating ability of phagocytes. These findings revealed that AA-C has not only the ATRA-enhanced cytotoxic effect but also the remarkable enhancing effect on the ATRA-induced O2--generating ability via up-regulating transcription of gp91-phox gene.

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© 2024 The Japanese Society of Toxicology
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