4‑methylumbelliferone inhibits clonogenic potency by suppressing high molecular weight‑hyaluronan in fibrosarcoma cells
| Autor: | Yoichiro Hosokawa, Rei Takahashi, Ryo Saga, Kazuhiko Okumura, Kazuki Hasegawa, Roman Fukui, Mitsuru Chiba, Eichi Tsuruga |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
inflammatory cytokine Cancer Research 4-methylumbelliferone Proinflammatory cytokine hyaluronan 03 medical and health sciences 0302 clinical medicine medicine Fibrosarcoma Clonogenic assay Matrigel biology interleukin Chemistry Articles medicine.disease Molecular medicine Hyaluronan synthase 030104 developmental biology Oncology 030220 oncology & carcinogenesis Cancer cell biology.protein Cancer research HT1080 |
| Zdroj: | Oncology Letters |
| ISSN: | 1792-1082 1792-1074 |
| Popis: | The inflammatory response is closely associated with cancer cell survival. It has been reported that inflammatory signaling cascades promote tumor survival and exert detrimental effects in normal tissue. Hyaluronans have different cellular functions depending on their molecular weights and high molecular weight-hyaluronan (HMW-HA) exhibits anti-inflammatory effects. A previous study determined that the co-administration of 4-methylumbelliferone (4-MU) and X-ray irradiation enhanced anti-tumor and anti-inflammatory effects in HT1080 human fibrosarcoma cells. However, many mechanisms underlie the effect of hyaluronan molecular weight on cells and the induction of anti-inflammatory effects via 4-MU. The present study aimed to determine the relationship between hyaluronan synthesis inhibition by 4-MU and its anti-inflammatory and radio-sensitizing effect in the context of hyaluronan molecular weight. The hyaluronan concentration following 2 Gy X-ray irradiation and/or 4-MU administration was analyzed via ELISA. Additionally, the mRNA expressions of hyaluronan synthase (HAS) by 4-MU and various inflammatory cytokines and interleukins (IL) following exogenous HMW-HA administration were evaluated via Reverse transcription-quantitative PCR. Invasive potential was assessed by matrigel transwell assays and cell survival following exposure to 4-MU with HMW-HA was determined using a clonogenic potency assay. The results of the present study demonstrated that 4-MU suppressed HMW-HA production by inhibiting HAS2 and HAS3 expression. In addition, the surviving fraction of fibrosarcoma cells were rescued from the cell-killing effect of 4-MU via the exogenous administration of HMW-HA. The mRNA levels of certain inflammatory cytokines, including IL-1α, IL-36γ and IL-37 were elevated following HMW-HA administration. The surviving fraction of cells irradiated with 2 Gy alone did not increase following exogenous HMW-HA administration. The results of the present study indicated that the radio-sensitizing effect of 4-MU and the inhibitory effect on hyaluronan synthesis were not closely associated. It was also revealed that IL-1α, IL-36γ and IL-37 were associated with the cell-killing effect of 4-MU in HT1080 cells. |
| Databáze: | OpenAIRE |
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