Resistance of Mitochondrial DNA-depleted Cells against Cell Death

Park, Sun Young; Chang, Inik; Kim, Ja Young; Kang, Sang Won; Park, Seho; Singh, Keshav K.; Lee, Myung-Shik

doi:10.1074/jbc.m307677200

Cited by 168 publications

(151 citation statements)

References 57 publications

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“…Although very little is known about the effects of cisplatin on the mitochondria of tumor cells (36), a recent study showed that it might have direct impact on mitochondria in head and neck cancer (37). Mitochondrial defects are associated with the cisplatin resistance phenotype (38), and several hypotheses have been suggested to explain this observation.…”

Section: Resultsmentioning

confidence: 99%

Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate

Dhar¹,

Lippard

2009

Proc. Natl. Acad. Sci. U.S.A.

343

236

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Section: Resultsmentioning

confidence: 99%

Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate

Dhar¹,

Lippard

2009

Proc. Natl. Acad. Sci. U.S.A.

343

236

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“…47 In addition, HO-1 has been identified as an inducer of Mn-SOD. 24 To explore the involvement of HIF-1a in Mn-SOD expression, we examined Mn-SOD levels in OSCC cells that were transfected with HIF-1a expression vector or HIF-1a-siRNA. The results showed that the Mn-SOD levels in the OSCC cells were upregulated by the transfection of HIF-1a expression vector and conversely downregulated by the siRNA.…”

Section: Discussionmentioning

confidence: 99%

The involvement of hypoxia‐inducible factor‐1α in the susceptibility to γ‐rays and chemotherapeutic drugs of oral squamous cell carcinoma cells

Sasabe

Zhou

et al. 2006

Intl Journal of Cancer

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The transcription factor hypoxia-inducible factor-1a (HIF-1a) is the key regulator that controls the hypoxic response of mammalian cells. The overexpression of HIF-1a has been demonstrated in many human tumors. However, the role of HIF-1a in the therapeutic efficacy of chemotherapy and radiotherapy in cancer cells is poorly understood. In this study, we investigated the influence of HIF-1a expression on the susceptibility of oral squamous cell carcinoma (OSCC) cells to chemotherapeutic drugs (cis-diamminedichloroplatinum and 5-fluorouracil) and c-rays. Treatment with chemotherapeutic drugs and c-rays enhanced the expression and nuclear translocation of HIF-1a, and the susceptibility of OSCC cells to the drugs and c-rays was negatively correlated with the expression level of HIF-1a protein. The overexpression of HIF-1a induced OSCC cells to become more resistant to the anticancer agents, and down-regulation of HIF-1a expression by small interfering RNA enhanced the susceptibility of OSCC cells to them. In the HIF-1a-knockdown OSCC cells, the expression of P-glycoprotein, heme oxygenase-1, manganese-superoxide dismutase and ceruloplasmin were downregulated and the intracellular levels of chemotherapeutic drugs and reactive oxygen species were sustained at higher levels after the treatment with the anticancer agents. These results suggest that enhanced HIF-1a expression is related to the resistance of tumor cells to chemo-and radio-therapy and that HIF-1a is an effective therapeutic target for cancer treatment. ' 2006 Wiley-Liss, Inc.Key words: hypoxia-inducible factor-1a; chemotherapeutic drugs; g-rays; P-glycoprotein; heme oxygenase-1 Solid tumors generally possess hypoxic areas in their central portion because of decreased vascular supply associated with the effects of treatment and the originally increased energy demand of cancer cells, and the hypoxic tissue is one of the serious matters for consideration in the control of malignant tumors. Most tumor cells possess the ability to undergo apoptosis in response to hypoxic conditions. However, tumor cells can adapt to hypoxic conditions by employing a variety of survival tools, which result in the promotion of cancer cell growth and metastasis. [1][2][3] This adaptation of cancer cells to hypoxia is mainly mediated by the transcription factor hypoxia-inducible factor-1 (HIF-1). 4 HIF-1 is a heterodimeric transcription factor consisting of an oxygen-regulated a subunit (HIF1a) and a stable nuclear factor, HIF-1b/aryl hydrocarbon receptor nuclear translocator (ARNT). Under normoxic conditions, HIF-1a is rapidly degraded by the proteosome after being targeted for ubiquitination. HIF-1a translocates to the nucleus under hypoxic conditions and forms an active complex with HIF-1b; the complex binds to the hypoxia-response element (HRE) in the target genes, which results in the transactivation of these genes. 5 Proteins encoded by such genes contribute to the blood supply, energy production, growth/survival, invasion/metastasis and resistance.It has been frequently rep...

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“…To detect ROS in vivo, fresh frozen tissue sections were incubated with 10 mM DHE solution (Invitrogen) at 37°C for 30 min (ref. 64). After washing with PBS, sections were examined on a fluorescent microscope.…”

Section: Methodsmentioning

confidence: 99%

Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes

et al. 2014

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Despite growing interest in the relationship between autophagy and systemic metabolism, how global changes in autophagy affect metabolism remains unclear. Here we show that mice with global haploinsufficiency of an essential autophagy gene (Atg7 þ / À mice) do not show metabolic abnormalities but develop diabetes when crossed with ob/ob mice. Atg7 þ / À -ob/ob mice show aggravated insulin resistance with increased lipid content and inflammatory changes, suggesting that autophagy haploinsufficiency impairs the adaptive response to metabolic stress. We further demonstrate that intracellular lipid content and insulin resistance after lipid loading are increased as a result of autophagy insufficiency, and provide evidence for increased inflammasome activation in Atg7 þ / À -ob/ob mice. Imatinib or trehalose improves metabolic parameters of Atg7 þ / À -ob/ob mice and enhances autophagic flux. These results suggest that systemic autophagy insufficiency could be a factor in the progression from obesity to diabetes, and autophagy modulators have therapeutic potential against diabetes associated with obesity and inflammation.

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Resistance of Mitochondrial DNA-depleted Cells against Cell Death

Cited by 168 publications

References 57 publications

Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate

Mitaplatin, a potent fusion of cisplatin and the orphan drug dichloroacetate

The involvement of hypoxia‐inducible factor‐1α in the susceptibility to γ‐rays and chemotherapeutic drugs of oral squamous cell carcinoma cells

Systemic autophagy insufficiency compromises adaptation to metabolic stress and facilitates progression from obesity to diabetes

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