Mechanism of hydrogen peroxide-induced apoptosis of the human osteosarcoma cell line HS-Os-1

Ogawa, Yasuhiro; Takahashi, Toshiaki; Kobayashi, Toshihiro; Kariya, Shuji; Nishioka, Akihito; Mizobuchi, Hiroo; Noguchi, Masataka; Hamasato, Shinji; Tani, Tohru; Seguchi, Harumichi; Shoji, Yasuhiro; Shinmoto, Hiroshi

doi:10.3892/ijmm.12.4.459

Cited by 6 publications

(9 citation statements)

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“…An interaction at a cellular level between H 2 O 2 and ionizing radiation (IR) was first reported in osteosarcoma (HS-Os-1) and prostate cancer (PC-3) cell lines, which demonstrated extreme resistance to either H 2 O 2 or 30 Gy alone. 6,7 The addition of 0.1 mM H 2 O 2 before IR resulted in enhanced cytotoxicity without causing DNA double strand breaks that classically mediate cell killing. 8,9 A novel mechanism was postulated to involve lysosomal membrane rupture with release of powerful oxidants, including heavy metal ions that permeabilize mitochondria and activate apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial

Nimalasena

Gothard

Anbalagan

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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Purpose: Hydrogen peroxide (H 2 O 2) plays a vital role in normal cellular processes but at supraphysiological concentrations causes oxidative stress and cytotoxicity, a property that is potentially exploitable for the treatment of cancer in combination with radiation therapy (RT). We report the first phase 1 trial testing the safety and tolerability of intratumoral H 2 O 2 þ external beam RT as a novel combination in patients with breast cancer and exploratory plasma marker analyses investigating possible mechanisms of action. Methods and Materials: Twelve patients with breast tumors !3 cm (surgically or medically inoperable) received intratumoral H 2 O 2 with either 36 Gy in 6 twice-weekly fractions (n Z 6) or 49.5 Gy in 18 daily fractions (n Z 6) to the whole breast AE

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Section: Introductionmentioning

confidence: 99%

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial

Nimalasena

Gothard

Anbalagan

et al. 2020

International Journal of Radiation Oncology*Biology*Physics

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“…Continuously elevated H 2 O 2 levels can promote the survival of tumor cells and may therefore promote tumor cell ability to adapt to the tumor microenvironment. However, high levels of H 2 O 2 can also (32) reported that potent oxidative stress caused by exogenous H 2 O 2 induces the apoptosis of human OS cells. A recent study also demonstrated that treatment with H 2 O 2 at a concentration of 100 µM resulted in a significant decrease in OS cell viability and an increase in apoptosis (9).…”

Section: Discussionmentioning

confidence: 99%

“…Park ( 31 ) reported that 100 µM H 2 O 2 suppressed the proliferation of lung cancer cells by arresting the cell cycle and inducing cells necrosis or apoptosis. In 2003, Ogawa et al ( 32 ) reported that potent oxidative stress caused by exogenous H 2 O 2 induces the apoptosis of human OS cells. A recent study also demonstrated that treatment with H 2 O 2 at a concentration of 100 µM resulted in a significant decrease in OS cell viability and an increase in apoptosis ( 9 ).…”

Section: Discussionmentioning

confidence: 99%

circKMT2D contributes to H<sub>2</sub>O<sub>2</sub>‑attenuated osteosarcoma progression via the miR‑210/autophagy pathway

et al. 2020

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Circular RNAs (circRNAs) have been demonstrated to be involved in osteosarcoma (OS) development; however, the underlying mechanism of circKMT2D in OS progression remains unclear. The present study aimed to elucidate how circKMT2D could affect hydrogen peroxide (H 2 O 2)-induced OS progression. H 2 O 2 (100 µmol/l) was used to treat MG63 and U2OS cells. The cell viability, invasive ability, apoptosis and circKMT2D expression were detected using Cell Counting Kit-8 assay, Transwell assay, flow cytometry and reverse transcription-quantitative PCR, respectively. Furthermore, MG63 and U2OS cells transfected with circKMT2D short hairpin RNA and negative control were treated with H 2 O 2 , and circKMT2D expression and cell phenotype were determined. Dual-luciferase reporter assay was conducted to determine the association between circKMT2D and miR-210 expression level. Rescue experiments were conducted to examine the mechanisms through which circKMT2D and miR-210 could affect H 2 O 2-treated MG63 cells. In addition, the effects of miR-210 on the expression of the autophagy-related proteins Beclin1 and p62 in H 2 O 2-treated MG63 cells were detected by western blotting. An autophagy inhibitor was used to treat the MG63 cells, and whether miR-210 could affect the H 2 O 2-treated MG63 cell phenotype through autophagy was investigated. The results demonstrated that H 2 O 2 treatment promoted cell apoptosis and decreased cell viability, invasive ability and circKMT2D expression in MG63 and U2OS cells. Furthermore, circKMT2D knockdown decreased the cell viability and invasive ability and enhanced the apoptosis of H 2 O 2-treated MG63 and U2OS cells. circKMT2D possessed binding sites for miR-210 and inhibited miR-210 expression. In H 2 O 2-treated MG63 cells, miR-210 silencing partially reversed the circKMT2D knockdown-induced cell viability inhibition and apoptosis promotion. In addition, miR-210 elevated Beclin1 expression and decreased p62 expression in H 2 O 2-treated MG63 cells. The use of the autophagy inhibitor partially reversed the miR-210 overexpression-induced promotion of apoptosis and inhibition of the viability and invasive ability of H 2 O 2-treated MG63 cells. Taken together, these findings indicated that circKMT2D knockdown may contribute to the inhibition of H 2 O 2-attenuated OS progression via miR-210/autophagy pathway.

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“…Moreover, a decrease in DNA ladder formation after treatment with Triol confirms that Triol-exposed cells are more resistant to apoptosis. This suggests that Triol-induced cytotoxicity may operate via similar mechanisms with apoptosis induction-related oxidative stress [24, 25]. Nevertheless, cell death of 70% in Triol-exposed cells after treatment with 30 μM Triol using SRB with undetectable DNA laddering could happen due to a discrepancy between the two methods.…”

Section: Discussionmentioning

confidence: 99%

Anti-apoptotic phenotypes of cholestan-3β,5α,6β-triol-resistant human cholangiocytes: Characteristics contributing to the genesis of cholangiocarcinoma

Jusakul¹,

Loilome²,

Namwat³

et al. 2013

The Journal of Steroid Biochemistry and Molecular Biology

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The oxysterols cholestan-3β, 5α, 6β-triol (Triol) and 3-keto-cholest-4-ene (3K4) are increased in Opisthorchis viverrini-associated hamster cholangiocarcinoma and induce DNA damage and apoptosis via a mitochondria-dependent mechanism in MMNK-1 human cholangiocytes. Based on these observations, we hypothesized that chronic exposure of cholangiocytes to these pathogenic oxysterols may allow a growth advantage to a subset of these cells through selection for resistance to apoptosis, thereby contributing to cholangiocarcinogenesis. To test this hypothesis, we cultured MMNK-1 cells long-term in the presence of Triol. Alteration in survival and apoptotic factors of Triol-exposed cells were examined. Cells cultured long-term in the presence of Triol were resistant to H2O2-induced apoptosis, and demonstrated an increase in the phosphorylation of p38-α, CREB, ERK1/2 and c-Jun. Elevations in the ratio of Bcl-2/Bax and in the protein levels of anti-apoptotic factors including cIAP2, clusterin, and survivin were detected. These results show that long-term exposure of MNNK-1 cells to low doses of Triol selects for kinase-signaling molecules with regulate resistance to apoptosis and thereby enhance cell survival. Clonal expansion of such apoptosis-resistant cells may contribute to the genesis of cholangiocarcinoma.

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Mechanism of hydrogen peroxide-induced apoptosis of the human osteosarcoma cell line HS-Os-1

Cited by 6 publications

References 0 publications

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial

Intratumoral Hydrogen Peroxide With Radiation Therapy in Locally Advanced Breast Cancer: Results From a Phase 1 Clinical Trial

circKMT2D contributes to H<sub>2</sub>O<sub>2</sub>‑attenuated osteosarcoma progression via the miR‑210/autophagy pathway

Anti-apoptotic phenotypes of cholestan-3β,5α,6β-triol-resistant human cholangiocytes: Characteristics contributing to the genesis of cholangiocarcinoma

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