Sanggenon C induces apoptosis of colon cancer cells via inhibition of NO production, iNOS expression and ROS activation of the mitochondrial pathway

Chen, Lidong; Liu, Zhihui; Zhang, Lianfeng; Yao, Jianning; Wang, Chunfeng

doi:10.3892/or.2017.5912

Cited by 31 publications

(29 citation statements)

References 29 publications

(33 reference statements)

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“…Mitochondrial membrane permeabilization (MMP) is closely associated with cancer cell death. Mitochondrial Ca 2+ overload drives ROS generation, triggering MMP and release of pro-apoptotic factors, leading to cell apoptosis and death ( 21 ). Furthermore, high concentrations of NO derived from iNOS inhibit the expression of Bcl-2, activate caspase and subsequently promote the release of cytochrome c , leading to cell death ( 22 ).…”

Section: Discussionmentioning

confidence: 99%

Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway

2018

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Cucurbitacin D (CuD), isolated from plants from the Cucurbitaceae family, is a potential antitumour agent since it inhibits proliferation, migration and metastasis of cancer cells. Despite CuD antitumour activity in cancer cells, the effects of CuD on gastric cancer cell lines remain unclear. The present study aimed to investigate the effects of CuD on gastric cancer cell growth and death. Human gastric cancer cell lines (AGS, SNU1 and Hs746T) were cultured and treated with different concentrations of CuD (0, 0.25, 0.5, 1 and 2 µM). Cell proliferation was assessed using Cell Counting Kit-8 assay. Oxidative stress was evaluated by generation of reactive oxygen species (ROS). Cell apoptosis was assessed by terminal deoxynucleotidyl transferase 2′-deoxyuridine-5′-triphosphate nick-end labelling (TUNEL) staining. Levels of intracellular Ca2+ and adenosine triphosphate (ATP) were also assessed. In the present study, CuD effectively inhibited cell proliferation, triggered ROS generation and induced apoptosis in gastric cancer cells (AGS, SNU1 and Hs746T). Treatment with CuD increased intracellular Ca2+ and ATP levels. CuD also stimulated the expression of inducible nitric oxide synthase (iNOS), which augmented nitric oxide production. In addition, CuD activated the mitochondrial apoptosis pathway, which increased the expression of Bax and the release of cleaved caspace-9 (C-caspase-9) and cytochrome c, decreased the expression of B-cell lymphoma 2 (Bcl-2). The mechanism of action of CuD involved the regulation of the protein kinase B/mechanistic target of rapamycin (Akt/mTOR) pathway. We confirmed the effects of CuD on gastric tumours via an in vivo xenograft gastric tumour model. In conclusion, CuD inhibited Akt and activated the iNOS pathway, leading to higher ROS and nitric oxide production, which accelerated gastric cancer cell apoptosis.

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Section: Discussionmentioning

confidence: 99%

Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway

2018

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“…Our preliminary study found that water extract and ethanol extract of Cortex Mori could stimulate MC3T3-E1 cells and inhibit osteoclast in vitro. Sanggenon C (C 40 H 36 O 12 , Figure 1 ), which is a main active flavanone originating from Cortex Mori, has been found to possess antioxidant, anti-inflammatory, and antitumor properties [ 7 , 8 , 9 , 10 , 11 , 12 ]. There was evidence that the increase reactive oxygen species (ROS) level and the inflammatory response were shown to be directly related to the osteoporosis [ 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Sanggenon C Stimulates Osteoblastic Proliferation and Differentiation, Inhibits Osteoclastic Resorption, and Ameliorates Prednisone-Induced Osteoporosis in Zebrafish Model

et al. 2018

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Sanggenon C (SC), which is a natural flavonoid found in the stem bark of Cortex Mori, has been discovered to have the antioxidant, anti-inflammatory, and antitumor properties. However, its effect in osteoporosis has not yet been reported. In this research, the effect of SC on the proliferation of MC3T3-E1 cells was evaluated by using the MTT assay. Alkaline phosphatase (ALP) activity and the mRNA expression of Runx2, Collagen I, OPG, and RANKL were examined. TRAP-positive cell counting and bone resorption pits were adopted to observe the effect of SC on the formation and function of osteoclasts. Next, the mRNA level of TRAP, CTSK, NFATc1, and TRAF6 of osteoclasts were measured by real-time qPCR. In addition, the anti-osteoporosis activity of SC in vivo was evaluated in the zebrafish model. Our study indicated that SC exhibited a significant stimulatory effect on MC3T3-E1 cell proliferation at 1 to 10 μM and caused an increase in ALP activity at 0.3 to 10 μM. It could upregulate the expression of Runx2, Collagen I, and increases the OPG/RANKL ratio. Furthermore, SC was found to inhibit the formation and function of osteoclasts, which is demonstrated by a lower number of TRAP-positive multinuclear cells and a fewer area of bone resorption pits compared to the control group. TRAP, CTSK, and NFATc1 were downregulated in 0.3 to 10 μM SC treated groups. In addition, 3 to 10 μM SC also inhibited the expression of TRAF6 mRNA. When prednisone-induced zebrafish was treated with 0.3, 1, 3, and 10 μM SC, higher mineralization of vertebrate column was discovered in a dose-dependent pattern, which suggests that SC could reverse the bone loss of zebrafish caused by prednisone. In summary, these findings indicated that SC has the potential to prevent or treat osteoporosis.

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“…NO and ROS was free radicals that are synthesized by iNOS [14]. iNOS and COX-2 are major inflammatory factors.…”

Section: Resultsmentioning

confidence: 99%

Pseudane-VII Regulates LPS-Induced Neuroinflammation in Brain Microglia Cells through the Inhibition of iNOS Expression

Kim

Jung

et al. 2018

Molecules

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We previously isolated pseudane-VII from the secondary metabolites of Pseudoalteromonas sp. M2 in marine water, and demonstrated its anti-inflammatory efficacy on macrophages. However, the molecular mechanism by which pseudane-VII suppresses neuroinflammation has not yet been elucidated in brain microglia. Microglia is activated by immunological stimulation or brain injury. Activated microglia secrete proinflammatory mediators which damage neurons. Neuroinflammation appears to be associated with certain neurological diseases, including Parkinson’s disease and Alzheimer’s disease. Natural compounds that suppress microglial inflammatory responses could potentially be used to prevent neurodegenerative diseases or slow their progression. In the present study, we found that pseudane-VII suppresses neuroinflammation in lipopolysaccaride (LPS)-stimulated BV-2 microglial cells and brain. Pseudane-VII was shown to inhibit the LPS-stimulated NO, ROS production and the expression of iNOS and COX-2. To identify the signaling pathway targeted by pseudane-VII, we used western blot analysis to assess the LPS-induced phosphorylation state of p38, ERK1/2, JNK1/2, and nuclear factor-kappaB (NF-κB). We found that pseudane-VII attenuated LPS-induced phosphorylation of MAPK and NF-κB. Moreover, administration of pseudane-VII in mice significantly reduced LPS-induced iNOS expression and microglia activation in brain. Taken together, our findings suggest that pseudane-VII may represent a potential novel target for treatment for neurodegenerative diseases.

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Sanggenon C induces apoptosis of colon cancer cells via inhibition of NO production, iNOS expression and ROS activation of the mitochondrial pathway

Cited by 31 publications

References 29 publications

Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway

Cucurbitacin D impedes gastric cancer cell survival via activation of the iNOS/NO and inhibition of the Akt signalling pathway

Sanggenon C Stimulates Osteoblastic Proliferation and Differentiation, Inhibits Osteoclastic Resorption, and Ameliorates Prednisone-Induced Osteoporosis in Zebrafish Model

Pseudane-VII Regulates LPS-Induced Neuroinflammation in Brain Microglia Cells through the Inhibition of iNOS Expression

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