A novel synthetic chalcone derivative promotes caspase-dependent apoptosis through ROS generation and activation of the UPR in MH7A cells

Kim, Jin-Hyun; Jeon, Yong-Joon; Cho, Jaewook; Shin, Jong-Il; Baek, Chae Yun; Lim, Yoongho; Koh, Dongsoo; Shin, Soon Young; Lee, Young Han; Lee, Kyung-Ho

doi:10.1007/s13258-015-0350-x

Cited by 4 publications

(4 citation statements)

References 38 publications

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“…In our study, EJT extract treatment increased the expression of ER stress related to ATF4 and CHOP, and the expression of CHOP was associated with EJT extract-induced apoptosis in MH7A cells. These results were consistent with our previous studies in MH7A cells of apoptosis induced by hemp seed oil (HO) or chalcone-derived DK-59 treatment and the apoptotic role of CHOP [ 53 , 54 ]. CHOP is known to be the major regulator of the apoptotic pathway under ER stress conditions.…”

Section: Discussionsupporting

confidence: 93%

Apoptotic and Anti-Inflammatory Effects of Eupatorium japonicum Thunb. in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Shin

Jeon

Lee

et al. 2018

BioMed Research International

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovitis, hyperplasia, and the destruction of bone and cartilage. A variety of immunosuppressive biological agents have been developed because the pathogenesis of RA is related predominantly to the inflammatory response. However, rheumatoid arthritis fibroblast-like synovial cells (RAFLS), which are known to play an important role in RA progression, exhibit resistance to immunosuppressants through cancer-like properties. In this study, we identified a novel therapeutic compound for RA, which reduced inflammation and the abnormal proliferation of RAFLS in natural product library made from Korean native plants. Eupatorium japonicum Thunb. (EJT) extract, a component of the natural product library, most effectively reduced viability through the induction of ROS-mediated apoptosis in a dose-dependent manner. In addition, the increased ROS induced the expression of ATF4 and CHOP, key players in ER stress-mediated apoptosis. Interestingly, EJT extract treatment dose-dependently reduced the expression of IL-1β and the transcription of MMP-9, which were induced by TNF-α treatment, through the inhibition of NF-κB and p38 activation. Collectively, we found that EJT extract exerted apoptotic effects through increases in ROS production and CHOP expression and exerted anti-inflammatory effects through the suppression of NF-κB activation, IL-1β expression, and MMP-9 transcription.

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Section: Discussionsupporting

confidence: 93%

Apoptotic and Anti-Inflammatory Effects of Eupatorium japonicum Thunb. in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Shin

Jeon

Lee

et al. 2018

BioMed Research International

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“…Later, in 2015, Kim et al investigated the effects of a novel chalcone derivative named (E)-3-(3,5-dimethoxyphenyl)-1-(1-hydroxynaphthalen-2-yl)-prop-2-en-1-one (DK-59, 33) on MH7A cells. The results showed that DK-59 reduced cell viability and induced ROS production and apoptosis in MH7A cells via up-regulating ATF4 and CHOP, activating Caspase-7 and PARP, as well as increasing phosphorylation of eIF2α [120]. Similarly, the extracts of Eupatorium japonicum Thunb (EJTE, 37.5 µg/mL) also showed apoptosis inducing activities in RA-FLS via ERS-mediated apoptotic pathway, such as up-regulation of ATF4 and CHOP [121].…”

Section: Ers Mediated Apoptotic Pathwaymentioning

confidence: 96%

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

et al. 2019

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Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

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“…For example, BPIQ, a quinoline derivative, induces ROS production in retinoblastoma cells [ 28 ]. ( E )-3-(3,5-dimethoxyphenyl)-1-(1-hydroxynaphthalen-2-yl) prop-2-en-1-one can evoke ROS burst in rheumatoid arthritis fibroblast-like synoviocytes [ 34 ]. The chalcone derivative S17 shows ROS generation in gastric cancer cells [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

Synthesis and Anticancer Evaluation of 4-Anilinoquinolinylchalcone Derivatives

Yang

Lee

Chen

et al. 2023

IJMS

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A series of 4-anilinoquinolinylchalcone derivatives were synthesized and evaluated for antiproliferative activities against the growth of human cancer cell lines (Huh-7 and MDA-MB-231) and normal lung cells (MRC-5). The results exhibited low cytotoxicity against human lung cells (MRC-5). Among them, (E)-3-{4-{[4-(benzyloxy)phenyl]amino}quinolin-2-yl}-1-(4-methoxyphenyl) prop-2-en-1-one (4a) was found to have the highest cytotoxicity in breast cancer cells and low cytotoxicity in normal cells. Compound 4a causes ATP depletion and apoptosis of breast cancer MDA-MB-231 cells and triggers reactive oxygen species (ROS)-dependent caspase 3/7 activation. In conclusion, it is worth studying 4-anilinoquinolinylchalcone derivatives further as new potential anticancer agents for the treatment of human cancers.

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A novel synthetic chalcone derivative promotes caspase-dependent apoptosis through ROS generation and activation of the UPR in MH7A cells

Cited by 4 publications

References 38 publications

Apoptotic and Anti-Inflammatory Effects of Eupatorium japonicum Thunb. in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Apoptotic and Anti-Inflammatory Effects of Eupatorium japonicum Thunb. in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Apoptosis Induction of Fibroblast-Like Synoviocytes Is an Important Molecular-Mechanism for Herbal Medicine along with its Active Components in Treating Rheumatoid Arthritis

Synthesis and Anticancer Evaluation of 4-Anilinoquinolinylchalcone Derivatives

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