Upregulation of both heme oxygenase-1 and ATPase inhibitory factor 1 renders tumoricidal activity by synthetic flavonoids via depleting cellular ATP

Lee, Phil Jun; Shin, Iljin; Seo, Seung‐Yong; Kim, Hyoungsu; Kim, Hong Pyo

doi:10.1016/j.bmcl.2014.08.055

Cited by 14 publications

(12 citation statements)

References 24 publications

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“…ROS are produced by all aerobic cells to regulate cell development, growth, survival and death. ROS normally exists in balance with biochemical antioxidants in all aerobic cells [18][19][20]. When this critical balance is disrupted by excess ROS production and/or antioxidant depletion, oxidative stress may come to exist [21,22].…”

Section: Discussionmentioning

confidence: 99%

Pectolinarigenin Suppresses the Tumor Growth in Nasopharyngeal Carcinoma

Wang

Cheng

Liu

et al. 2016

Cell Physiol Biochem

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Background/Aims: Nasopharyngeal cancer (NPC) is one of the common human malignant diseases all over the world, and chemotherapy remains the main therapy for NPC. However, the survival and life quality of NPC patients are still very poor. Thus, novel and selective anti-tumor agents are pressingly needed. Our previous study identified pectolinarigenin as a novel effective anti-tumor drug candidate for NPC. In this study, we further investigated its anti-tumor activities and explored the potential molecular mechanism. Methods: NPC C666-1 cells were cultured and treated by pectolinarigenin. Cell proliferation assay, colony formation assay, Transwell assay and wound healing assay were conducted and cell apoptosis was detected by flow cytometry. Mitochondrial transmembrane potential and ROS were also observed. NPC subcutaneous xenograft mice model was established to evaluate the anti-tumor effect of pectolinarigenin in vivo. Results: We observed that treatment of pectolinarigenin inhibited cell viability and cell migration of NPC C666-1 cells in concentration- and time-dependent manner. Pectolinarigenin induced cell apoptosis in C666-1 cells detected by flow cytometry analysis, which was associated with the activation of mitochondrial-related apoptosis and the accumulation of reactive oxygen species (ROS). Pectolinarigenin also activated caspase signaling pathway. The in vivo experiment of subcutaneous xenograft mice model also indicated that the administration of pectolinarigenin could decrease the tumor growth of NPC and no severe toxicity was observed. Conclusions: Based on our findings, we conclude that pectolinarigenin could suppress the tumor growth of NPC, which verifies it as a new therapeutic agent for treating this devastating disease.

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Section: Discussionmentioning

confidence: 99%

Pectolinarigenin Suppresses the Tumor Growth in Nasopharyngeal Carcinoma

Wang

Cheng

Liu

et al. 2016

Cell Physiol Biochem

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“…[10][11][12] For example, its antioxidant, antiapoptotic, and anti-inflammatory effects have been extensively studied. 12,13 The cytoprotective effect of HO-1 could have several distinct underlying mechanisms, including degradation of heme to the antioxidant bilirubin; coordinated induction of ferritin, which chelates the pro-oxidant free iron; and release of CO, which exerts significant antioxidant effects. 12,13 Our previous study showed the ameliorative effects of betulin, isolated from Betula platyphylla bark, on scopolamineinduced amnesic mice.…”

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confidence: 99%

Betulin Protects HT-22 Hippocampal Cells against ER Stress through Induction of Heme Oxygenase-1 and Inhibition of ROS Production

Lee

Park

Yoo

et al. 2019

Natural Product Communications

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A key pathologic event in neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease, is endoplasmic reticulum (ER) stress-induced neuronal cell death. ER stress-induced generation of reactive oxygen species (ROS) has been implicated in neurological disease processes. Betulin is one of the major triterpenoids found in Betula platyphylla that possesses several biological properties, including cytoprotective and antioxidative effects. Therefore, we investigated whether betulin could prevent ER stress-induced neurotoxicity in HT-22 hippocampal neuronal cells. We observed that betulin reduced the thapsigargin (TG, an ER stress inducer)-induced apoptosis of HT-22 cells. Moreover, the cytoprotective effects of betulin were comparable to those of tauroursodeoxycholic acid, a potent ER stress-reducing agent. In our study, we confirmed that the ER stress-induced accumulation of ROS plays an important role in HT-22 cell death. Betulin also displayed cytoprotective effects in TG-injured HT-22 cells by reducing ROS generation; these results were comparable to those for N-acetyl-L-cysteine, a known ROS inhibitor. In addition, SnPP, a heme oxygenase-1 (HO-1) inhibitor significantly blocked the cytoprotective effects and ROS scavenging activity of betulin. Based on these results, we believe that betulin-mediated induction of HO-1 may contribute to the neuroprotective effects against ER stress in HT-22 hippocampal cells. We also found that betulin significantly inhibited the TG-induced expression of CHOP and caspase-12. These results demonstrated that betulin could serve as a potential therapeutic agent against ER stress-induced neurodegenerative diseases.

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“…Known chrysin derivatives 2–6 were prepared from chrysin (1) according to the procedure previously described in the literature (Kim et al ., 2014; Lee et al ., 2014a; Lee et al ., 2014b; Baek et al ., 2015). C(5) benzyl- and 4-substituted benzyl-protected chrysin derivatives 7–11 were prepared using conventional synthetic methods in three steps (MOM protection of chrysin, benzylation, and deprotection of MOM group) as described in Fig.…”

Section: Methodsmentioning

confidence: 99%

“…However, no studies on the anti-CVB3 activity of chrysin and its derivatives have been reported to date. Continuing our efforts towards the synthesis and biological evaluation of flavonoid-based natural products (Kim et al ., 2014; Lee et al ., 2014a; Lee et al ., 2014b; Baek et al ., 2015), we embarked on the synthesis of chrysin derivatives and studied the antiviral effect of chrysin and its derivatives against CVB3. Herein, we report the antiviral activity of chrysin-derivatives against CVB3 in vitro and in vivo .…”

Section: Introductionmentioning

confidence: 99%

Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo

Song

Kwon

Jang

et al. 2015

Biomolecules & Therapeutics

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Chrysin is a 5,7-dihydroxyflavone and was recently shown to potently inhibit enterovirus 71 (EV71) by suppressing viral 3C protease (3Cpro) activity. In the current study, we investigated whether chrysin also shows antiviral activity against coxsackievirus B3 (CVB3), which belongs to the same genus (Enterovirus) as EV71, and assessed its ability to prevent the resulting acute pancreatitis and myocarditis. We found that chrysin showed antiviral activity against CVB3 at 10 μM, but exhibited mild cellular cytotoxicity at 50 μM, prompting us to synthesize derivatives of chrysin to increase the antiviral activity and reduce its cytotoxicity. Among four 4-substituted benzyl derivatives derived from C(5) benzyl-protected derivatives 7, 9–11 had significant antiviral activity and showed the most potent activity against CVB3 with low cytotoxicity in Vero cells. Intraperitoneal injection of CVB3 in BALB/c mice with 1×106 TCID50 (50% tissue culture infective dose) of CVB3 induced acute pancreatitis with ablation of acinar cells and increased serum CXCL1 levels, whereas the daily administration of 9 for 5 days significantly alleviated the pancreatic inflammation and reduced the elevation in serum CXCL1 levels. Collectively, we assessed the anti-CVB3 activities of chrysin and its derivatives, and found that among 4-substituted benzyl derivatives, 9 exhibited the highest activity against CVB3 in vivo, and protected mice from CVB3-induced pancreatic damage, simultaneously lowering serum CXCL1 levels.

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Upregulation of both heme oxygenase-1 and ATPase inhibitory factor 1 renders tumoricidal activity by synthetic flavonoids via depleting cellular ATP

Cited by 14 publications

References 24 publications

Pectolinarigenin Suppresses the Tumor Growth in Nasopharyngeal Carcinoma

Pectolinarigenin Suppresses the Tumor Growth in Nasopharyngeal Carcinoma

Betulin Protects HT-22 Hippocampal Cells against ER Stress through Induction of Heme Oxygenase-1 and Inhibition of ROS Production

Antiviral Activity of Chrysin Derivatives against Coxsackievirus B3 in vitro and in vivo

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