No Influence of Exogenous Hyaluronan on the Behavior of Human Cancer Cells or Endothelial Cell Capillary Formation

Seino, Satoshi; Takeshita, Fumitaka; Asari, Akira; Masuda, Yasunobu; Kunou, Masaaki; Ochiya, Takahiro

doi:10.1111/1750-3841.12500

Cited by 6 publications

(5 citation statements)

References 32 publications

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“…Interestingly, the results revealed that treatment with HA of different sizes had no specific effect on CRC malignancy. This finding is consistent with some recent reports that the HA ligand‐related pathway has no effect on regulating cellular behavior …”

Section: Discussionsupporting

confidence: 93%

“…This finding is consistent with some recent reports that the HA ligand-related pathway has no effect on regulating cellular behavior. 37,38 Our results demonstrated that secreted HA ligand has less influence on CRC; however, overexpressed HAS2 regulates CRC malignancy crucially. This led us to postulate that HAS2 has a specific role in CRC malignancy regulation independent of HA synthase.…”

Section: Overexpression Of Has2 Mediates Colorectal Cancer Malignanmentioning

confidence: 72%

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Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

et al. 2019

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Hyaluronic acid synthase 2 (HAS2) is suggested to play a critical role in malignancy and is abnormally expressed in many carcinomas. However, its role in colorectal cancer (CRC) malignancy and specific signaling mechanisms remain obscure. Here, we report that HAS2 was markedly increased in both CRC tissue and malignant CRC cell lines. Depletion of HAS2 in HCT116 and DLD1 cells, which express high levels of HAS2, critically increased sensitivity of radiation/oxaliplatin‐mediated apoptotic cell death. Moreover, downregulation of HAS2 suppressed migration, invasion and metastasis in nude mice. Conversely, ectopic overexpression of HAS2 in SW480 cells, which express low levels of HAS2, showed the opposite effect. Notably, HAS2 loss‐ and gain‐of‐function experiments revealed that it regulates CRC malignancy through TGF‐β expression and SMAD2/Snail downstream components. Collectively, our findings suggest that HAS2 contributes to malignant phenotypes of CRC, at least partly, through activation of the TGF‐β signaling pathway, and shed light on the novel mechanisms behind the constitutive activation of HAS2 signaling in CRC, thereby highlighting its potential as a therapeutic target.

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Section: Discussionsupporting

confidence: 93%

Section: Overexpression Of Has2 Mediates Colorectal Cancer Malignanmentioning

confidence: 72%

Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

et al. 2019

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“… 26 In addition, various safety studies were also conducted, and safety was confirmed. 27 – 37 Therefore, HA can be said to be a food material, which is suitable for long-term continuous intake.…”

Section: Discussionmentioning

confidence: 99%

Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

Oe¹,

Sakai²,

Yoshida³

et al. 2017

CCID

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BackgroundHyaluronan (HA) has critical moisturizing property and high water retention capacity especially for human skin. This study aimed to evaluate the effect of oral intake of HA.MethodsThe mean molecular weight (MW) of HA is 2 k and 300 k. Sixty Japanese male and female subjects aged 22–59 years who presented with crow’s feet wrinkles were randomly assigned to the HA 2 k or HA 300 k at 120 mg/day or the placebo group. The subjects were administered HA at a rate of 120 mg/day or a placebo for 12 weeks. The skin wrinkles were evaluated by image analysis of skin wrinkle replicas, and their skin condition was evaluated using a questionnaire survey.ResultsDuring the study period, the HA groups showed better level of the whole sulcus volume ratio, wrinkle area ratio, and wrinkle volume ratio than the placebo group. After 8 weeks of ingestion, the HA 300 k group showed significantly diminished wrinkles compared with the placebo group. Skin luster and suppleness significantly improved after 12 weeks in all groups compared with the baseline.ConclusionThe results suggest that oral HA (both HA 2 k and HA 300 k) inhibits skin wrinkles and improves skin condition.

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“…No toxicity was observed in single-dose toxicity studies [ 48 – 50 ], repeated-dose toxicity studies [ 51 – 61 ], reproductive and developmental toxicity studies [ 62 – 69 ], mutagenicity tests [ 70 – 74 ], and antigenicity studies [ 75 , 76 ]. It is reported that exogenous HA such us that administered orally is not harmful to human cancer cells [ 77 ]. A 12 month clinical study identified no adverse event attributable to HA [ 41 ].…”

Section: Safety Of Hamentioning

confidence: 99%

Oral hyaluronan relieves knee pain: a review

Oe¹,

Tashiro

Yoshida³

et al. 2015

Nutr J

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Hyaluronan (HA) is a component that is particularly abundant in the synovial fluid. Randomized, double-blinded, placebo-controlled trials carried out between 2008 and 2015 have proven the effectiveness of HA for the treatment of symptoms associated with synovitis, and particularly, knee pain, relief of synovial effusion or inflammation, and improvement of muscular knee strength. The mechanism by which HA exerts its effects in the living body, specifically receptor binding in the intestinal epithelia, has gradually been clarified. This review examines the effects of HA upon knee pain as assessed in clinical trials, as well as the mechanism of these effects and the safety of HA.

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No Influence of Exogenous Hyaluronan on the Behavior of Human Cancer Cells or Endothelial Cell Capillary Formation

Abstract: Orally administered hyaluronan was recently found to have beneficial effects. However, the effect of exogenous hyaluronan on cancer remains unclear. Our findings support the safety of orally administered hyaluronan and its use as a functional food ingredient.

Cited by 6 publications

References 32 publications

Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

Hyaluronic acid synthase 2 promotes malignant phenotypes of colorectal cancer cells through transforming growth factor beta signaling

Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period

Oral hyaluronan relieves knee pain: a review

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