Aqueous extracts of Paeonia suffruticosa modulates mitochondrial proteostasis by reactive oxygen species-induced endoplasmic reticulum stress in pancreatic cancer cells

Liu, Yu Huei; Weng, Yu-I; Tsai, Hsin Ying; Chen, Chao‐Jung; Lee, Der Yen; Hsieh, Ching-Liang; Wu, Yang Chang; Lin, Jung‐Yaw

doi:10.1016/j.phymed.2018.03.037

Cited by 23 publications

(28 citation statements)

References 28 publications

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“…When cells are subjected to strong external environmental stress, the unfolded or misfolded proteins accumulate in the ER, causing ER stress. Many drugs, such as bortezomib 17 , suffruticosa aqueous extracts 32 and apatinib 18 , cause ER stress and then induce apoptosis. Similar to these reports, our study also found that anlotinib induced increases in BiP, PERK and CHOP, which are ER stress biomarker proteins.…”

Section: •−mentioning

confidence: 99%

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

et al. 2020

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Anlotinib (AL3818), a novel multi-targeted receptor tyrosine kinase inhibitor, has recently been proven to be an antitumour drug. This study aimed to explore the antitumour effect of anlotinib and its underlying molecular mechanisms in human pancreatic cancer (PC) cells. The anti-proliferative effect of anlotinib for three PC cell lines was validated using CCK-8, colony formation and EdU detection assays. Cell cycle, cell apoptosis, and reactive oxygen species (ROS) detection assays, a PC xenograft model and immunohistochemistry were performed to elucidate the mechanisms by which anlotinib induced tumour lethality in vitro and in vivo. These results demonstrated that anlotinib inhibited proliferation, induced G2/M phase arrest and triggered apoptosis in PC cell lines. Anlotinib induced PC’s apoptosis through the accumulation of ROS which activated the endoplasmic reticulum (ER) stress via PERK/p-eIF2α/ATF4 pathway. Furthermore, we demonstrated that the expression level of Nrf2, an antioxidant protein, increased with anlotinib treatment. Nrf2 knockdown enhanced the pro-apoptotic effect of anlotinib and the expression of the PERK/p-eIF2α/ATF4 pathway. The in vivo results suggested that suppressing Nrf2 improved the antitumour effect of anlotinib on PC cells. These data indicated that the apoptotic effect of anlotinib on PC cells was induced by ER stress via the accumulation of ROS. In the future, anlotinib combined with an Nrf2 inhibitor may provide a new therapeutic strategy for the treatment of human PC.

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Section: •−mentioning

confidence: 99%

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

et al. 2020

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“…3). In our previous publication, the PGG concentration in WE was measured as www.nature.com/scientificreports/ 975.90 ± 14.10 ppb (1.04 ± 0.02 μM) 13 . The amount of PGG in the working concentration of WE was ~ 25 nM and much lower than the IC 50 of synthetic PGG compound, suggesting that PGG may not be the major contributor in MDP anti-inflammatory activity.…”

Section: Discussionmentioning

confidence: 99%

“…However, both TCM preparations derived from MDP demonstrated therapeutic effects in colitis, suggesting that both have therapeutic activities. In reference to our measurement of concentrations of PGG in WE 13 , the Figure 6. WE but not PGG strongly inhibits NF-κB and IRF signaling pathways.…”

Section: Discussionmentioning

confidence: 99%

A systematic identification of anti-inflammatory active components derived from Mu Dan Pi and their applications in inflammatory bowel disease

Chen

Hsu

et al. 2020

Sci Rep

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Mu Dan Pi (MDP), also known as Moutan Cortex Radicis, is a traditional Chinese medicine used to treat autoimmune diseases. However, the impact of MDP and its principal active compounds on inflammatory bowel disease (IBD) is uncertain. This study therefore systemically assessed the anti-inflammatory effects of MDP and its known active compounds in IBD. The anti-inflammatory activities of water extract and individual compounds were screened by NF-κB and interferon regulatory factor (IRF) reporter assays in THP-1 cells induced with either Toll-like receptor or retinoic acid inducible gene I/melanoma differentiation-associated gene 5 activators and further verified in bone marrow-derived macrophages. MDP water extract significantly inhibited the activation of NF-κB and IRF reporters, downstream signaling pathways and the production of IL-6 and TNF-α, in a dose-dependent manner. Among 5 known active components identified from MDP (1,2,3,4,6-penta-O-galloyl-β-d-glucose [PGG], gallic acid, methyl gallate, paeoniflorin, and paeonol), PGG was the most efficient at inhibiting both reporters (with an IC50 of 5–10 µM) and downregulating IL-6 and TNF-α. Both MDP powder for clinical use and MDP water extract, but not PGG, reduced colitis and pathological changes in mice. MDP and its water extract show promise as a novel therapy for IBD patients.

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“…Several pharmacological effects can be mediated by P. suffruticosa, including antispasmodic, antidiabetic [56], anti-inflammatory [57], antioxidant, anticancer [58], and antimelanogenic effects [59]. The effects of P. suffruticosa aqueous extracts on the survival, proliferation, and migration of pancreatic cancer (PC) cells (i.e., PANC1, AsPC1, and BxPC3) were evaluated by Liu et al [60]. Treatment with P. suffruticosa (25-2500 μg/ml, for 24 h) decreased cell survival in a dose-dependent manner through an increased expression of LC3-II, a reduced expression of MFN2 and MFN1, and the promotion of mitophagy through an increased autophagosome and autolysosome formation.…”

mentioning

confidence: 99%

“…Treatment with P. suffruticosa (25-2500 μg/ml, for 24 h) decreased cell survival in a dose-dependent manner through an increased expression of LC3-II, a reduced expression of MFN2 and MFN1, and the promotion of mitophagy through an increased autophagosome and autolysosome formation. Additionally, P. suffruticosa inhibited cell cycle progression and cell migration through the downregulation of cyclin and cyclindependent kinase (CDK) and the stabilization of F-actin cytoskeleton [60].…”

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confidence: 99%

Effects of Plant and Animal Natural Products on Mitophagy

Shakeri

Bianconi

Pirro

et al. 2020

Oxidative Medicine and Cellular Longevity

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Mitophagy is a protected cellular process that is essential for autophagic removal of damaged mitochondria and for preservation of a healthy mitochondrial population. In the last years, a particular interest has been devoted in studying the effects of natural compounds on mitophagy. Different natural compounds may modulate mitochondrial oxidative phosphorylation, the production of mitochondrial reactive oxygen species, the expression of mitophagy-and autophagy-related genes, and the activities of transcription factors which regulate the expression of mitochondrial proteins, thereby controlling mitochondrial damage and mitophagy. Remarkably, since mitochondrial function has a crucial role in the pathogenesis of various diseases (e.g., cancer, atherosclerosis, Duchenne muscular dystrophy, diabetes complications, Alzheimer's disease, and hepatic steatosis), these effects might have important therapeutic implications. In this review, preclinical studies investigating the role of different natural compounds in the modulation of mitophagy will be discussed.

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Aqueous extracts of Paeonia suffruticosa modulates mitochondrial proteostasis by reactive oxygen species-induced endoplasmic reticulum stress in pancreatic cancer cells

Cited by 23 publications

References 28 publications

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

Reactive oxygen species mediate anlotinib-induced apoptosis via activation of endoplasmic reticulum stress in pancreatic cancer

A systematic identification of anti-inflammatory active components derived from Mu Dan Pi and their applications in inflammatory bowel disease

Effects of Plant and Animal Natural Products on Mitophagy

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