Plant flavonoid taxifolin inhibits the growth, migration and invasion of human osteosarcoma cells

Chen, Xin; Gu, Na; Xue, Chao; Li, Ban‐Ruo

doi:10.3892/mmr.2017.8271

Cited by 38 publications

(34 citation statements)

References 27 publications

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“…), Laric siberica (ledeb.) and Texus chinensis, was demonstrated to inhibit osteosarcoma cell proliferation and suppress tumor growth in nude mice xenograft model through AKT/MYC inhibition (26). In line with the above context, the present study provides a detail of a key molecular mechanism by which gigantol suppresses MYC and supports its potential use and development for cancer treatment (Figure 8).…”

Section: Discussionsupporting

confidence: 80%

Gigantol Targets MYC for Ubiquitin-proteasomal Degradation and Suppresses Lung Cancer Cell Growth

Losuwannarak

Roytrakul

Chanvorachote

2020

Cancer Genomics Proteomics

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Background: Gigantol is a pharmacologically active bibenzyl compound exerting potential anticancer activities. At non-toxic concentrations, it reduces cancer stem cell properties and tumorigenicity. The mechanisms of the effects of gigantol on cancer cell growth are largely unknown. This study aimed to unravel the molecular profile and identify the prominent molecular mechanism of the effects of gigantol in controlling lung cancer cell proliferation. Materials and Methods: Proteomics and bioinformatics analysis were used accompanied by experimental molecular pharmacology approaches. Results: Gigantol exhibited antiproliferative effects on human lung cancer cells confirmed by 3-(4, 5dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide proliferation assay and colony growth assay. The protein profile in response to gigantol treatment associated with regulation of cell proliferation was analyzed to determine the prominent protein targets. Among the significant hub proteins, MYC, an important proto-oncogene and proliferationpromoting transcription factor, was down-regulated with the highest number of protein-protein interactions. MYC downregulation was confirmed by western blot analysis. The upstream regulator of MYC, Glycogen synthase kinase 3 beta (GSK3β) was found to be responsible for MYC destabilization mediated by gigantol. Gigantol facilitated GSK3β function and resulted in the increase of MYC-ubiquitin complex as evaluated by immunoprecipitation. Conclusion: Gigantol was found to inhibit lung cancer proliferation through induction of GSK3β-mediated MYC ubiquitin-proteasome degradation. These data suggest gigantol to be a promising candidate for novel strategy in inhibition of lung cancer. Evading growth suppression and sustaining proliferation are among the hallmarks of cancer and lead to disease progression (1). Cell proliferation is an increase in the number of cells as a result of cell growth and cell division, and rapid proliferation is considered an aggressive factor of cancer and is correlated with poor prognosis (2, 3). Dysregulation of proliferation signals and oncogenes is known to drive carcinogenesis and tumor growth (4, 5). There are several oncogenes that control cancer cell growth. MYC, a proto-oncogene, is a central transcription factor that controls cell proliferation, differentiation, and apoptosis. Amplification or overexpression of MYC occurs in various cancer types, including lung cancer, and was shown to be related to poor survival (6). An inhibition of MYC may offer an effective therapeutic treatment via tumor growth suppression (7, 8). However, as targeted therapy against MYC is still elusive due to its lack of inhibitory binding site, modulation of the MYC level via targeting its upstream regulators is a potential strategy (6). Glycogen synthase kinase 3 beta (GSK3β) showed prominent tumorsuppressor properties in lung cancer (9). Protein kinase B (AKT1)-dependent GSK3β phosphorylation at Ser9 was shown to be correlated with poor survival rate of patients with lung cancer (10). GSK3β s...

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Section: Discussionsupporting

confidence: 80%

Gigantol Targets MYC for Ubiquitin-proteasomal Degradation and Suppresses Lung Cancer Cell Growth

Losuwannarak

Roytrakul

Chanvorachote

2020

Cancer Genomics Proteomics

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“…The anti-cancer effects of SLM and silibinin on salivary gland cancer have also been reported by Choi et al (2017) [ 34 ]. Chen et al (2018) showed that taxifolin suppressed the proliferation of human osteosarcoma cells [ 35 ]. Alzaharna et al (2017) demonstrated that taxifolin induced apoptosis and autophagy cell death in HeLa cells [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

et al. 2018

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Background and objective: Previous studies have demonstrated the anti-cancer effects of silymarin (SLM). However, the low bioavailability of SLM has restricted its use. This study investigated the toxic effect of nanostructured SLM encapsulated in micelles (Nano-SLM) on the growth of the HT-29 human colon cancer cell line. Materials and methods: HT-29 cells were treated with 25 μM/mL of SLM or Nano-SLM for 48 h. MTT and colony formation assays were used to assess the cytotoxicity and proliferation of HT-29 cells, respectively. The cells were stained with annexin V/PI for assessment of apoptosis. Results: MTT assays revealed that Nano-SLM treatment was able to exert a more pronounced toxic effect on the HT-29 cells as compared to free SLM treatment (p < 0.01). In the Nano-SLM-treated cells, colony numbers were significantly reduced in comparison to the free SLM-treated cells (p < 0.01). Apoptotic and necrotic indexes of Nano-SLM-treated HT-29 cells were also significantly increased in comparison to those of the free SLM-treated cells (p < 0.01). The viability, proliferation and apoptosis of healthy cells (NIH-3T3 cells) were not changed in response to Nano-SLM or SLM. Conclusions: Our results indicate that Nano-SLM enhances the anti-cancer effects of SLM against human colon cancer cells.

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“…Taxifolin (3,3′,4′,5,7-pentahydroxiflavanon), a flavanone found in onions, milk thistle, French maritime, and Douglas fir bark, has a known antioxidant activity [9, 10]. Furthermore, previous studies suggested that taxifolin was effective against various types of cancer [11, 12]. Thus, the literature suggests that taxifolin may reduce lung toxicity without suppressing the anticancer effects of cisplatin, possibly potentiating its anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

The Effect of Taxifolin on Cisplatin-Induced Pulmonary Damage in Rats: A Biochemical and Histopathological Evaluation

Ünver

Tosun

Ölmez

et al. 2019

Mediators of Inflammation

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The effect of taxifolin on cisplatin-induced oxidative pulmonary damage was investigated biochemically and histopathologically in male albino Wistar rats. There were four groups, with six animals in each group: 50 mg/kg of taxifolin plus 2.5 mg/kg of cisplatin (TC) group, 2.5 mg/kg of cisplatin only (CIS) group, 50 mg/kg of taxifolin only (TG) group, and a healthy control group (HG). In terms of the experimental procedure, the animals in the TC and TG groups were first treated via oral gavage. The CIS and HG groups received distilled water as solvent, respectively. One hour later, the TC and CIS groups received cisplatin at a dose of 2.5 mg/kg (injected intraperitoneally). Taxifolin, cisplatin, and the distilled water were administered at the indicated dose and volume, using the same method daily for 14 d. At the end of this period, the animals were killed with a high dosage of thiopental anaesthesia (50 mg/kg). Blood and lung tissue samples were taken for biochemical (malondialdehyde (MDA), myeloperoxidase (MPO), total glutathione (tGSH), and 8-hydroxy-2 deoxyguanosine (8-OHdG)) analyses and histopathological examinations. The biochemical and histopathological results in the TC and HG groups were then compared with those in the CIS group. Cisplatin increased the levels of MDA, myeloperoxidase, and 8-OHdG, a marker of oxidative DNA damage, and reduced the amount of tGSH in the lung tissue. Moreover, severe alveolar damage, including oedema and extensive alveolar septal fibrosis, in addition to infiltration of polymorphic nuclear leucocytes and haemorrhagic foci, was observed in the CIS group. These histopathological findings demonstrate that taxifolin provides protection against pulmonary oxidative stress by preventing increases in oxidant parameters and decreases in antioxidants.

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Plant flavonoid taxifolin inhibits the growth, migration and invasion of human osteosarcoma cells

Cited by 38 publications

References 27 publications

Gigantol Targets MYC for Ubiquitin-proteasomal Degradation and Suppresses Lung Cancer Cell Growth

Gigantol Targets MYC for Ubiquitin-proteasomal Degradation and Suppresses Lung Cancer Cell Growth

Effects of Silymarin-Loaded Nanoparticles on HT-29 Human Colon Cancer Cells

The Effect of Taxifolin on Cisplatin-Induced Pulmonary Damage in Rats: A Biochemical and Histopathological Evaluation

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