Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE

Indo, Hiroko P.; Inanami, Osamu; Koumura, Tomoko; Suenaga, Shigeaki; Yen, Hsiu-Chuan; Kakinuma, Shizuko; Matsumoto, Ken‐ichiro; Nakanishi, Ikuo; Clair, William St; Clair, Daret K. St.; Matsui, Hirofumi; Cornette, Richard; Gusev, Oleg; Okuda, Takashi; Nakagawa, Yasuhito; Ozawa, Toshihiko; Majima, Hideyuki J.

doi:10.3109/10715762.2012.698012

Cited by 45 publications

(22 citation statements)

References 39 publications

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“…Overexpression of MnSOD reduces tumor multiplicity, incidence, and metastatic ability in various in vitro and in vivo models (50). Accumulating evidence show that MnSOD is implicated in the resistance of tumor cells to some therapies, such as chemo- and radio-therapy through scavenging cellular ROS produced by mitochondria oxidative phosphorylation (51, 52). In mice lacking SIRT3, the ability of MnSOD to reduce cellular ROS and promote oxidative stress resistance is greatly enhanced by SIRT3 (53), indicating that SIRT3-MnSOD pathway is a pro-survival network in cancer cells.…”

Section: Discussionmentioning

confidence: 99%

CDK1-Mediated SIRT3 Activation Enhances Mitochondrial Function and Tumor Radioresistance

Fan

Candas

et al. 2015

Molecular Cancer Therapeutics

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The tumor adaptive resistance to therapeutic radiation remains to be a barrier for further improvement of local cancer control. SIRT3, a member of the sirtuin family of NAD+-dependent protein deacetylases in mitochondria, promotes metabolic homeostasis through regulation of mitochondrial protein deacetylation and plays a key role in prevention of cell aging. Here, we demonstrate that SIRT3 expression is induced in an array of radiation-treated human tumor cells and their corresponding xenograft tumors including colon cancer HCT-116, glioblastoma U87 and breast cancer MDA-MB231 cells. The SIRT3 transcriptional activation is due to SIRT3 promoter activation controlled by the stress transcription factor NF-κB. Post-transcriptionally, the SIRT3 enzymatic activity is further enhanced via Thr150/Ser159 phosphorylation by Cyclin B1/CDK1, which is also induced by radiation and relocated to mitochondria together with SIRT3. Cells expressing the Thr150Ala/Ser159Ala mutant SIRT3 show a reduction in the mitochondrial protein lysine deacetylation, ΔΨm, MnSOD activity and mitochondrial ATP generation. The clonogenicity of Thr150Ala/Ser159Ala mutant transfectants is lower and significantly decreased under radiation. Tumors harboring the Thr150Ala/Ser159Ala mutant SIRT3 show inhibited growth and sensitivity to in vivo local irradiation. These results demonstrate that enhanced SIRT3 transcription and post-translational modifications in mitochondria contribute to the adaptive radioresistance in tumor cells. The CDK1-mediated SIRT3 phosphorylation is a potential effective target to sensitize tumor cells to radiotherapy.

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Section: Discussionmentioning

confidence: 99%

CDK1-Mediated SIRT3 Activation Enhances Mitochondrial Function and Tumor Radioresistance

Fan

Candas

et al. 2015

Molecular Cancer Therapeutics

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“…Our previous studies demonstrated that the increase in the post-irradiated levels of ROS was caused by the leakage of ROS from the mitochondria [3], and that the increase in intracellular ROS levels following irradiation occurred as a consequence of the upregulation of the mitochondrial ETC function and mitochondrial content in a fibroblast cell line, as well as in a variety of other tumor cell lines [4]. Wang and Yi [30] and Laurent et al [31] have proposed a new hypothesis, which is known as the ‘ROS threshold concept’, to further characterize the role of intracellular ROS in tumor cells [32].…”

Section: Discussionmentioning

confidence: 99%

“…There have been several reports in the literature demonstrating that the levels of intracellular reactive oxygen species (ROS) in human IM-9 multiple myeloma cells and immortalized mouse embryonic m5S cells increase several hours after cells have been irradiated [1, 2], and this increase in ROS levels has been attributed to the leakage of ROS from the mitochondria [3]. Increases in intracellular ROS levels of this type have been observed in a fibroblast cell line (NIH3T3 cells), as well as in a variety of different tumor cell lines (A549, HeLa, MKN45 and MeWo cells), following their exposure to X-ray radiation.…”

Section: Introductionmentioning

confidence: 99%

“…It has been suggested that the radiation-induced upregulation of the mitochondrial electron transport chain (ETC) function and mitochondrial content could be contributing to the increases in mitochondrial ROS levels [4]. Several recent reports have also suggested that the increases in intracellular ROS in irradiated cells occur in conjunction with or as a consequence of various other pathological events, such as the bystander effect [5, 6], genetic instability [1, 7–9], and apoptosis [3, 10–13]. …”

Section: Introductionmentioning

confidence: 99%

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3-Methyl pyruvate enhances radiosensitivity through increasing mitochondria-derived reactive oxygen species in tumor cell lines

Nishida

Yasui

Nagane

et al. 2014

Journal of Radiation Research

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Considerable interest has recently been focused on the special characteristics of cancer metabolism, and several drugs designed to modulate cancer metabolism have been tested as potential anticancer agents. To date, however, very few studies have been conducted to investigate the combined effects of anticancer drugs and radiotherapy. In this study, to evaluate the role of mitochondria-derived reactive oxygen species (ROS) in the radiation-induced cell death of tumor cells, we have examined the effect of 3-methyl pyruvate (MP). MP is a membrane-permeable pyruvate derivative that is capable of activating mitochondrial energy metabolism in human lung carcinoma A549 cells and murine squamous carcinoma SCCVII cells. Pretreatment with MP significantly enhanced radiation-induced cell death in both cell lines, and also led to increases in the mitochondrial membrane potential, intracellular adenosine triphosphate content, and mitochondria-derived ROS production following the exposure of the cells to X-rays. In A549 cells, MP-induced radiosensitization was completely abolished by vitamin C. In contrast, it was partially abolished in SCCVII cells. These results therefore suggest that the treatment of the cells with MP induced radiosensitization via the production of excess mitochondria-derived ROS in tumor cells.

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“…In other words, MnSOD is the specific scavenger of superoxides produced by mitochondrial electron transport [13]. It is interesting that a hundred times number of mitochondria is observed in oocytes compared to those in somatic cells [14].…”

Section: Source Of Reactive Oxygen Speciesmentioning

confidence: 95%

Involvement of Mitochondrial Reactive Oxygen Species in Gastric Carcinogenesis

Tamura¹

2013

J Gastrointest Dig Syst

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Gastric cancer is one of the most common malignancies in many countries. Environmental gastric cancer risk is known to be associated with Helicobacter pylori infection, a high intake of salty foods, and alcohol consumption. Here, we provide evidence of linkage of mitochondrial reactive oxygen species (ROS) to several environmental gastric cancer risks. Moreover, ROS correlate with gastric cancer invasion and metastasis, the most important factor to decide a patient's prognosis. We also show correlation between mitochondrial ROS and gastric cancer invasion by using a normal gastric mucosal cell line (RGM-1), a cancerous mutant RGM-1 subclonal (RGK-1) and a MnSOD-expressing RGK-1 cell-line, used for a scavenging mitochondrial ROS. This mini-review summarizes role of ROS in gastric carcinogenesis and aims to provide a clue in developing useful treatments against gastric cancer.

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Roles of mitochondria-generated reactive oxygen species on X-ray-induced apoptosis in a human hepatocellular carcinoma cell line, HLE

Cited by 45 publications

References 39 publications

CDK1-Mediated SIRT3 Activation Enhances Mitochondrial Function and Tumor Radioresistance

CDK1-Mediated SIRT3 Activation Enhances Mitochondrial Function and Tumor Radioresistance

3-Methyl pyruvate enhances radiosensitivity through increasing mitochondria-derived reactive oxygen species in tumor cell lines

Involvement of Mitochondrial Reactive Oxygen Species in Gastric Carcinogenesis

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