The dihydro-β-agarofuran sesquiterpenoids

Gao, Jin‐Ming; Wu, Wenjun; Zhang, Jiwen; Konishi, Yasuo

doi:10.1039/b601473a

Cited by 171 publications

(143 citation statements)

References 251 publications

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“…Pristimerin is a quinonemethide triterpenoid compound that has long been used as anti-inflammatory, antioxidant, antimalarial, and insecticidal agents (Brinker et al, 2007;Gao et al, 2007). Although pristimerin recently has been shown to induce apoptosis in certain cancer cells, the cell death mechanism by pristimerin is largely unknown.…”

Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species-Dependent Activation of Bax and Poly(ADP-ribose) Polymerase-1 Is Required for Mitochondrial Cell Death Induced by Triterpenoid Pristimerin in Human Cervical Cancer Cells

et al. 2009

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Naturally occurring triterpenoid compounds have long been used as anti-inflammatory, antimalarial, and insecticidal agents. It has become evident that some of the natural or synthetic triterpenoids have promising clinical potential as both a therapeutic and chemopreventive agent for cancer. However, the molecular basis for the antitumor activity of triterpenoid has yet to be defined. In this study, we show that pristimerin, a natural triterpenoid, induces mitochondrial cell death in human cervical cancer cells and that reactive oxygen species (ROS)-dependent activation of both Bax and poly(ADP-ribose) polymerase-1 (PARP-1) is critically required for the mitochondrial dysfunction. We also showed that c-Jun N-terminal kinase (JNK) is involved in ROS-dependent Bax activation. Treatment of pristimerin induced an increase in intracellular ROS, JNK activation, conformational change, and mitochondrial redistribution of Bax, mitochondrial membrane potential loss, and cell death. The PARP-1 was also found to be activated by pristimerin treatment. An antioxidant, N-acetyl-L-cysteine (NAC), inhibited pristimerin-induced JNK activation, Bax relocalization, and PARP-1 activation, as well as mitochondrial cell death. Moreover, inhibition of JNK clearly suppressed conformational change and mitochondrial translocation of Bax and subsequent mitochondrial cell death but did not affect PARP-1 activation. Inhibition of PARP-1 with 1,5-dihydroxyisoquinoline (DIQ) or with small interfering RNA of PARP-1 significantly attenuated pristimerininduced mitochondrial membrane potential loss and cell death but did not affect JNK activation and Bax relocalization. These results indicate that the natural triterpenoid pristimerin induces mitochondrial cell death through ROS-dependent activation of both Bax and PARP-1 in human cervical cancer cells and that JNK is involved in ROS-dependent Bax activation.

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Section: Discussionmentioning

confidence: 99%

Reactive Oxygen Species-Dependent Activation of Bax and Poly(ADP-ribose) Polymerase-1 Is Required for Mitochondrial Cell Death Induced by Triterpenoid Pristimerin in Human Cervical Cancer Cells

et al. 2009

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“…1) Pristimerin, a naturally occurring quinoneme thide triterpenoid compound, is a traditional medicine derived from the Celastraceae and Hippocrateacea families and has long been used as an anti-inflammatory, antioxidant, antima larial, and insecticidal agent. 2,3) Some of the plants containing pristimerin, such as Maytenus chuchuhuasca and Maytenus laevis, have been used traditionally to treat arthritis and skin cancer in South America. 4) Pristimerin has promising clinical potential as both a therapeutic and chemopreventive agent for various cancers.…”

mentioning

confidence: 99%

Anticancer Activity of Pristimerin in Epidermal Growth Factor Receptor 2-Positive SKBR3 Human Breast Cancer Cells

Lee

Yoon

Lee

et al. 2013

Biological & Pharmaceutical Bulletin

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Pristimerin is a naturally occurring triterpenoid that causes cytotoxicity in several cancer cell lines. However, the mechanism of action for the cytotoxic effect of pristimerin has not been unexplored. The purpose of this study was to investigate the effect of pristimerin on cytotoxicity using the epidermal growth factor receptor 2 (HER2)-positive SKBR3 human breast cancer cell line. Pristimerin inhibited proliferation in dose-and time-dependent manners in cells. We found it to be effective for suppressing HER2 protein and mRNA expression. Fatty acid synthase (FASN) expression and FASN activity were downregulated by pristimerin. Adding of exogenous palmitate, the end product of de novo fatty acid synthesis, reduced the proliferation activity of pristimerin. The changes in HER2 and FASN expression induced by pristimerin altered the levels of Akt and mitogen-activated protein kinase (MAPK) phosphorylation (Erk1/2, p38, and c-Jun N-terminal kinase (JNK)). Pristimerin lowered the levels of phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets such as phosphoprotein 70 ribosomal protein S6 kinase and 4E binding protein1. Pristimerin inhibited migration and invasion of cells, and co-treatment with the mTOR inhibitor rapamycin additionally suppressed these activities. Pristimerin-induced apoptosis was evaluated using Western blotting for caspase-3, -8, -9, and poly (ADP-ribose) polymerase expression and flow cytometric analysis for propidium iodide labeling. These results suggest that pristimerin is a novel HER2-downregulated compound that is able to decrease fatty acid synthase and modulate the Akt, MAPK, and mTOR signaling pathways to influence metastasis and apoptosis. Pristimerin may be further evaluated as a chemotherapeutic agent for HER2-positive breast cancers.

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“…Quinonemethide triterpenoids isolated from T. regelii such as celastrol, iguestein, pristimerin, and tingenone are reported to possess several biological activities such as anticancer, anti-inflammatory, antimalarial, antioxidant, antiviral, and insecticidal activities (Luo et al 2005;Brinker et al 2007;Gao et al 2007;Su et al 2009;Ryu et al 2010) as well as antifungal activity (Dos Santos et al 2010). Furthermore, these triterpenoids induced an increase in intracellular reactive oxygen species (ROS) and mitochondrial dysfunction (Byun et al 2009), and the quinonemethide moiety with electrochemical potential is regarded as a key component of the triterpenoid (Ryu et al 2010).…”

Section: Introductionmentioning

confidence: 99%

Downregulation of fungal cytochrome c peroxidase expression by antifungal quinonemethide triterpenoids

Seo

Lee

Park

et al. 2016

Journal of Applied Biological Chemistry

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To handle the development of antifungal drug resistance, the development of new structural modules and new modes of action for antifungals have been highlighted recently. Here, the antifungal activity of quinonemethidal triterpenoids such as celastrol, dihydrocelastrol, iguestein, pristimerin, and tingenone isolated from Tripterygium regelii were identified (MIC 0.269-19.02 µM). C. glabrata was the most susceptible to quinonemethide among the tested fungi. Furthermore, quinonemethide suppressed cyctochrome c peroxidase expression dramatically, decreasing fungal viability caused by the accumulation of hydrogen peroxide. Thus, cyctochrome c peroxidase downregulation of quinonemethide may be a key mode of action for antifungals.

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The dihydro-β-agarofuran sesquiterpenoids

Cited by 171 publications

References 251 publications

Reactive Oxygen Species-Dependent Activation of Bax and Poly(ADP-ribose) Polymerase-1 Is Required for Mitochondrial Cell Death Induced by Triterpenoid Pristimerin in Human Cervical Cancer Cells

Reactive Oxygen Species-Dependent Activation of Bax and Poly(ADP-ribose) Polymerase-1 Is Required for Mitochondrial Cell Death Induced by Triterpenoid Pristimerin in Human Cervical Cancer Cells

Anticancer Activity of Pristimerin in Epidermal Growth Factor Receptor 2-Positive SKBR3 Human Breast Cancer Cells

Downregulation of fungal cytochrome c peroxidase expression by antifungal quinonemethide triterpenoids

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