Ammonia mediates mitochondrial uncoupling and promotes glycolysis via HIF-1 activation in human breast cancer MDA-MB-231 cells

Lu, Yapeng; Wang, Lu; Ding, Wangwang; Wang, Dan; Wang, Xueting; Luo, Qianqian; Zhu, Li

doi:10.1016/j.bbrc.2019.08.152

Cited by 14 publications

(7 citation statements)

References 33 publications

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“…Hypoxia inducible factor‐1α (HIF‐1α) is another factor that can be targeted by CT. The stimulation of HIF‐1α enhances growth and proliferation of breast cancer cells by induction of glycolysis (Lu et al, 2019). MiR 17–92 recovers the sensitivity of cancer cells into radiotherapy by inhibition of HIF‐1α (Roudkenar et al, 2020).…”

Section: Cryptotanshinone and Cancermentioning

confidence: 99%

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Ashrafizadeh

Zarrabi

Orouei

et al. 2020

Phytotherapy Research

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In respect to the enhanced incidence rate of cancer worldwide, studies have focused on cancer therapy using novel strategies. Chemotherapy is a common strategy in cancer therapy, but its adverse effects and chemoresistance have limited its efficacy. So, attempts have been directed towards minimally invasive cancer therapy using plant derived‐natural compounds. Cryptotanshinone (CT) is a component of salvia miltiorrihiza Bunge, well‐known as Danshen and has a variety of therapeutic and biological activities such as antioxidant, anti‐inflammatory, anti‐diabetic and neuroprotective. Recently, studies have focused on anti‐tumor activity of CT against different cancers. Notably, this herbal compound is efficient in cancer therapy by targeting various molecular signaling pathways. In the present review, we mechanistically describe the anti‐tumor activity of CT with an emphasis on molecular signaling pathways. Then, we evaluate the potential of CT in cancer immunotherapy and enhancing the efficacy of chemotherapy by sensitizing cancer cells into anti‐tumor activity of chemotherapeutic agents, and elevating accumulation of anti‐tumor drugs in cancer cells. Finally, we mention strategies to enhance the anti‐tumor activity of CT, for instance, using nanoparticles to provide targeted drug delivery.

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Section: Cryptotanshinone and Cancermentioning

confidence: 99%

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Ashrafizadeh

Zarrabi

Orouei

et al. 2020

Phytotherapy Research

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“…22 Glycolysis of tumor cells can be used for energy supply to tumor cells by consuming glucose, and the generated lactic acid will be secreted outside the cell to promote the invasion and metastasis of tumor cells. 23 Therefore, digging deep into the upstream molecular mechanism of glycolysis in tumors is of great significance. In this study, downregulation of FOXO6 expression was found to inhibit the glycolysis in HCC cells significantly, which was reflected by an increase of glucose content in the cell culture medium, the decrease of lactic acid, and the decrease expressions of Glut1, HK2 and LDH-A protein in cells.…”

Section: Discussionmentioning

confidence: 99%

<p>Knockdown of FOXO6 Inhibits Glycolysis and Reduces Cell Resistance to Paclitaxel in HCC Cells via PI3K/Akt Signaling Pathway</p>

Gao

Mao

et al. 2020

OTT

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Purpose: Previous studies have reported that FOXO6 is highly expressed in hepatocellular carcinoma (HCC) tissues and is associated with the prognosis of HCC patients. However, little research has been carried out to explore the role of FOXO6 in glycolysis of HCC cells and paclitaxel resistance. Today, along with the increasing incidence and mortality of HCC, chemotherapy resistance of HCC also poses a serious challenge. Therefore, this study was set out to investigate the effect of FOXO6 on glycolysis and cytotoxicity of paclitaxel in HCC cells and its potential mechanism. Patients and Methods: The levels of FOXO6 mRNA and protein were detected by qRT-PCR and Western blot, respectively. In addition, paclitaxel-resistant cell lines of HCC cells were established, whose activity was assessed by CCK-8 assay, among which the invasion ability was assessed by Transwell and the apoptosis rate by flow cytometry. What is more, glycolysis levels were evaluated by measuring glucose consumption and lactic acid production, and the protein levels of p-PI3K and p-protein kinase B (Akt) were determined by Western blot. Results: Compared with normal human hepatocytes, FOXO6 was highly expressed in HCC cells, which was of high real value for HCC. FOXO6 knockdown inhibited the proliferation and invasion and induced apoptosis of HCC cells. In addition, FOXO6 knockdown suppressed glycolysis, reversed resistance to chemotherapy in Hep3B/PTX cells and inactivated PI3K and Akt proteins, thus inhibiting the PI3K/Akt signaling pathway. Furthermore, it was found that when activated by 740Y-P, PI3K/Akt signaling pathway could resist the effects of FOXO6 knockdown on the cytotoxicity and glycolysis of paclitaxel in HCC cells. Vice versa, inhibition of PI3K/Akt pathway by LY294002 could resist the effect of FOXO6 overexpression on chemotherapy, cytotoxicity and glycolysis of HCC cells. Conclusion: FOXO6 knockdown can inhibit glycolysis of HCC cells and reduce their resistance to chemotherapy by inhibiting the PI3K/Akt signaling pathway, which may be a new target for the treatment of HCC.

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“…HIF-1 is a heterodimer composed of HIF-1α and HIF-1β ( Fig. 1) (8,9). Under normoxic (21% O 2 ) conditions, HIF-1 is degraded by intracellular oxygen-dependent ubiquitin protease degradation pathways, which are inhibited during hypoxia (8,10).…”

Section: Structural Characteristics Of Hif-1mentioning

confidence: 99%

“…1) (8,9). Under normoxic (21% O 2 ) conditions, HIF-1 is degraded by intracellular oxygen-dependent ubiquitin protease degradation pathways, which are inhibited during hypoxia (8,10). HIF-1α is a hypoxia inducible transcription factor that contains two transactivation domains (C-TAD and N-TAD) (11,12).…”

Section: Structural Characteristics Of Hif-1mentioning

confidence: 99%

“…Oxygen-dependent degradation domain, another special structure of HIF-1α, participates in mediating the degradation of HIF-1 (9). It is worth noting that HIF-1α must form a heterodimer with HIF-1β before exerting its biological function (8). HIF-1β is stably expressed in cells and maintains the stability of HIF-1 (21,22).…”

Section: Structural Characteristics Of Hif-1mentioning

confidence: 99%

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Role of hypoxia inducible factor-1 in cancer stem cells (Review)

et al. 2020

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Cancer stem cells (CSCs) have been found to play a decisive role in cancer recurrence, metastasis, and chemo-, radio-and immuno-resistance. Understanding the mechanism of CSC self-renewal and proliferation may help overcome the limitations of clinical treatment. The microenvironment of tumor growth consists of a lack of oxygen, and hypoxia has been confirmed to induce cancer cell invasion, metastasis and epithelial-mesenchymal transition, and is usually associated with poor prognosis and low survival rates. Hypoxia inducible factor-1 (HIF-1) can be stably expressed under hypoxia and act as an important molecule to regulate the development of CSCs, but the specific mechanism remains unclear. The present review attempted to explain the role of HIF-1 in the generation and maintenance of CSCs from the perspective of epigenetics, metabolic reprogramming, tumor immunity, CSC markers, non-coding RNA and signaling pathways associated with HIF-1, in order to provide novel targets with HIF-1 as the core for clinical treatment, and extend the life of patients. Contents 1. Introduction 2. Structural characteristics of HIF-1 3. Role of epigenetic and post-translational modification of HIF-1 in CSCs 4. Role of HIF-1 in non-coding RNA associated with CSCs 5. Role of HIF-1 in CSC markers 6. Role of HIF-1 in tumor immunity of CSCs 7. Role of HIF-1 in metabolic reprogramming of CSCs 8. Role of HIF-1 in signaling pathways associated with CSCs 9. Potential targets for CSC therapy 10. Conclusions and perspectives

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Ammonia mediates mitochondrial uncoupling and promotes glycolysis via HIF-1 activation in human breast cancer MDA-MB-231 cells

Cited by 14 publications

References 33 publications

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

<p>Knockdown of FOXO6 Inhibits Glycolysis and Reduces Cell Resistance to Paclitaxel in HCC Cells via PI3K/Akt Signaling Pathway</p>

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

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Ammonia mediates mitochondrial uncoupling and promotes glycolysis via HIF-1 activation in human breast cancer MDA-MB-231 cells

Cited by 14 publications

References 33 publications

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

Recent advances and future directions in anti‐tumor activity of cryptotanshinone: A mechanistic review

<p>Knockdown of FOXO6 Inhibits Glycolysis and Reduces Cell Resistance to Paclitaxel in HCC Cells via PI3K/Akt Signaling Pathway</p>

Role of hypoxia inducible factor-1 in cancer stem cells (Review)

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Ammonia mediates mitochondrial uncoupling and promotes glycolysis via HIF-1 activation in human breast cancer MDA-MB-231 cells