Heme oxygenase-1 plays a crucial role in chemoresistance in acute myeloid leukemia

Zhe, Nana; Wang, Ji‐Shi; Chen, Shuya; Lin, Xiaojing; Chai, Qiang; Zhang, Yaming; Zhao, Jiangyuan; Fang, Qing

doi:10.1179/1607845414y.0000000212

Cited by 44 publications

(33 citation statements)

References 23 publications

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“…The drug-resistant acute myeloid leukemia (AML) cell line HL-60R is significantly less sensitive to cytarabine and daunorubicin than HL-60 cells and this correlates to HO-1 overexpression. Indeed, HO-1 downregulation significantly enhanced the sensitivity of HL-60R to chemotherapy [97]. Moreover, in the majority of AML patients, especially in those with acute monocytic leukemia and leukocytosis, HO-1 is aberrantly overexpressed.…”

Section: Ho-1 In Cancer Growth and Resistance To Therapymentioning

confidence: 99%

HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation

et al. 2017

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The upregulation of heme oxygenase-1 (HO-1) is one of the most important mechanisms of cell adaptation to stress. Indeed, the redox sensitive transcription factor Nrf2 is the pivotal regulator of HO-1 induction. Through the antioxidant, antiapoptotic, and antinflammatory properties of its metabolic products, HO-1 plays a key role in healthy cells in maintaining redox homeostasis and in preventing carcinogenesis. Nevertheless, several lines of evidence have highlighted the role of HO-1 in cancer progression and its expression correlates with tumor growth, aggressiveness, metastatic and angiogenetic potential, resistance to therapy, tumor escape, and poor prognosis, even though a tumor- and tissue-specific activity has been observed. In this review, we summarize the current literature regarding the pro-tumorigenic role of HO-1 dependent tumor progression as a promising target in anticancer strategy.

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Section: Ho-1 In Cancer Growth and Resistance To Therapymentioning

confidence: 99%

HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation

et al. 2017

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“…Cancer cells maintain a balance of ROS by activation of oxidative stress response genes, many of which are regulated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) [22, 23]. The increased expression of oxidative stress response genes contributes to cancer cell resistance to chemotherapies such as anthracyclines [24, 25], which work in part by inducing oxidative stress. Given the significant protection that adipocytes provide to ALL cells, particularly against the anthracycline daunorubicin (DNR) [16], we investigated whether adipocytes protect ALL cells from chemotherapies by relieving oxidative stress.…”

Section: Introductionmentioning

confidence: 99%

Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response

et al. 2016

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Adipocytes promote cancer progression and impair treatment, and have been shown to protect acute lymphoblastic leukemia (ALL) cells from chemotherapies. Here we investigate whether this protection is mediated by changes in oxidative stress. Co-culture experiments showed that adipocytes protect ALL cells from oxidative stress induced by drugs or irradiation. We demonstrated that ALL cells induce intracellular ROS and an oxidative stress response in adipocytes. This adipocyte oxidative stress response leads to the secretion of soluble factors which protect ALL cells from daunorubicin (DNR). Collectively, our investigation shows that ALL cells elicit an oxidative stress response in adipocytes, leading to adipocyte protection of ALL cells against DNR.

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“…3 Recently, studies have suggested that chemotherapy resistance is the main reason for the failure of chemotherapy and disease recurrence for AML patients. [4][5] The bone marrow microenvironment plays a critical role in the development, progression, and relapse of AML. 6 Haematopoietic stem cells (HSCs) and leukemia-initiating cells (LICs) reside in a hypoxic bone marrow niche.…”

Section: Introductionmentioning

confidence: 99%

HIF-1α inhibition by 2-methoxyestradiol induces cell death via activation of the mitochondrial apoptotic pathway in acute myeloid leukemia

Zhe

Chen

Zhou

et al. 2016

Cancer Biology & Therapy

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The bone marrow microenvironment plays an important role in the development and progression of AML. Leukemia stem cells are in a hypoxic condition, which induces the expression of HIF-1α. Aberrant activation of HIF-1α is implicated in the poor prognosis of patients with acute myeloid leukemia (AML). Herein, we investigated the expression of HIF-1α in AML and tested 2-methoxyestradiol (2ME2) as a candidate HIF-1α inhibitor for the treatment of AML. We found that HIF-1α was overexpressed in AML. HIF-1α suppression by 2ME2 significantly induced apoptosis of AML cells, and it outperformed traditional chemotherapy drugs such as cytarabine. At the same time, 2ME2 downregulated the transcriptional levels of VEGF, GLUT1 and HO-1 in cellular assays. Additionally, 2ME2 displayed antileukemia activity in bone marrow blasts from AML patients, but showed little effect on normal cells. 2ME2-induced activation of mitochondrial apoptotic pathway is mediated by reactive oxygen species (ROS), which decreased the slight effect of drug on normal cells. Our data show that supression of HIF-1α expression significantly reduced the survival of AML cell lines, suggesting that 2ME2 may represent a powerful therapeutic approach for patients with AML.

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Heme oxygenase-1 plays a crucial role in chemoresistance in acute myeloid leukemia

Cited by 44 publications

References 23 publications

HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation

HO-1 Induction in Cancer Progression: A Matter of Cell Adaptation

Adipocytes cause leukemia cell resistance to daunorubicin via oxidative stress response

HIF-1α inhibition by 2-methoxyestradiol induces cell death via activation of the mitochondrial apoptotic pathway in acute myeloid leukemia

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