HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma

Valladares, Katherine Julissa Palma; Balbinot, Karolyny Martins; Moraes, Antonia Taiane Lopes de; Kataoka, Maria Sueli da Silva; Ramos, Aline Maria Pereira Cruz; Ramos, Rommel Thiago Jucá; Silva, Artur da Costa da Luiz; Mesquita, Ricardo Alves; Normando, David; Júnior, Sérgio de Melo Alves; Pinheiro, João de Jesus Viana

doi:10.1155/2021/3060375

Cited by 10 publications

(15 citation statements)

References 33 publications

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“…In summary, these data suggested that α-hederin overcomes hypoxia-mediated resistance in CRC cells in vivo through the AKT/Bcl2 signalling pathway. between HIF-1α and Bcl2 (21). Herein, the expression levels of Bcl2 and Bcl-xL were observed to be positively correlated with the expression levels of HIF-1α in the collected clinical tissue samples, as demonstrated by IHC experiments, indicating that apoptosis inhibition was positively correlated with hypoxia (Fig.…”

Section: α-Hederin Overcomes Drug Resistance In Crc Cells Under Hypox...mentioning

confidence: 56%

α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway

Chen

Yang

et al. 2023

Int J Oncol

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Currently, chemoresistance is a major challenge that directly affects the prognosis of patients with colorectal cancer (CRC). In addition, hypoxia is associated with poor prognosis and therapeutic resistance in patients with cancer. Accumulating evidence has shown that α-hederin has significant antitumour effects and that α-hederin can inhibit hypoxia-mediated drug resistance in CRC; however, the underlying mechanism remains unclear. In the present study, viability and proliferation assays were used to evaluate the effect of α-hederin on the drug resistance of CRC cells under hypoxia. Sequencing analysis and apoptosis assays were used to determine the effect of α-hederin on apoptosis under hypoxia. Western blot analysis and reverse transcription-quantitative PCR were used to measure apoptosis-related protein and mRNA expression levels. Furthermore, different mouse models were established to study the effect of α-hederin on hypoxia-mediated CRC drug resistance in vivo. In the present study, the high expression of Bcl2 in hypoxic CRC cells was revealed to be a key factor in their drug resistance, whereas α-hederin inhibited the expression of Bcl2 by reducing AKT phosphorylation in vitro and in vivo, and promoted the apoptosis of CRC cells under hypoxia. By contrast, overexpression of AKT reversed the effect of α-hederin on CRC cell apoptosis under hypoxia. Taken together, these results suggested that α-hederin may overcome hypoxia-mediated drug resistance in CRC by inhibiting the AKT/Bcl2 pathway. In the future, α-hederin may be used as a novel adjuvant for reversing drug resistance in CRC.

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Section: α-Hederin Overcomes Drug Resistance In Crc Cells Under Hypox...mentioning

confidence: 56%

α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway

Chen

Yang

et al. 2023

Int J Oncol

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“…However, these cells are equidistant from the surrounding bone matrix so they would not receive as much stimulus resulting from bone resorption. Additionally, some studies have shown that in tumour microenvironments with hypoxia, there is an increase in apoptosis and the formation of cystic areas in the central portions of the CAM [10,22,23].…”

Section: Discussionmentioning

confidence: 99%

“…In addition, tumour cells typically demonstrate high demand for oxygen during proliferation, and access to oxygen in the central area of the tumour becomes restricted, which leads to the creation of hypoxic microenvironments [10]. This process occurs in most solid tumours and can result in an increase in aggressiveness at the front of tumour invasion (tumour periphery) [24] or lead to tumour death by apoptosis in the centre of the tumour [22]. This validates the result of quanti cation in different regions of the MUA, in which the highest rates of immunostaining for the apoptosis-promoting protein were found in the cystic lumen region (tumour centre).…”

Section: Discussionmentioning

confidence: 99%

“…Some studies have also concluded that there are more apoptosis-inhibiting than activating proteins, suggesting that conventional ameloblastoma parenchyma cells may have a high survival activity, and thus their high recurrence rate [8,22,25,26]. This can be attributable to a greater proliferation of CAM at the bone-neoplasm interface than at the centre of this tumour [22,24] By silencing an anti-apoptotic protein (Bcl-2) in an assay with ameloblastoma cells, Kim et al [25], observed that there was inhibition of tumour formation in vivo and suggest that studying apoptosis modulators may favour the prediction of recurrences and the development of effective chemotherapeutic agents for the treatment of these lesions.…”

Section: Discussionmentioning

confidence: 99%

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Cell proliferation and apoptosis immunolocalisation suggest an association between aggressiveness and the preferred location of mural unicystic ameloblastomas: A multicentricStudy

Costa

Balbinot

Silveira

et al. 2023

Preprint

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Objectives This study aimed to assess whether the different biological behaviour between subtypes of unicystic ameloblastoma (UA) are related to the expression of proteins that modulate cell proliferation and apoptosis. Materials and methods Immunohistochemical study with a sample of 32 cases of UA, 11 cases of conventional ameloblastoma (CAM) and 10 dental follicles (DF) cases was performed. Cell proliferation was assessed using Ki-67 status and apoptosis by expression of Caspase-3. Positive cells were quantified in each sample and the difference among groups was compared. Results Mural UA (MUA) showed a higher immunostaining of Ki-67 (p < 0.05) and a lower immunostaining of Caspase-3 (p < 0.05) compared to luminal and intraluminal subtypes of UA (LIUA) and CAM. For both proteins, the LIUA and CAM groups showed no statistical difference. The neoplastic cells of the cystic capsule of the MUA showed a higher expression of Ki-67 protein (p < 0.0001) and a lower expression of Caspase-3 (p < 0.0001) compared to the lumen. DF showed lower Ki-67 and Caspase-3 immunostaining (p < 0.05) than neoplasms, except when comparing Caspase-3 expression between DF and MUA, as there was no statistical difference. Conclusions The higher immunoexpression of Ki-67 and lower of Caspase-3 in MUA, in the parenchyma cells inside the cystic capsule, suggests an association between the biological behaviour and the location of neoplastic cells in the tumour.

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“…The ameloblastoma cell line was cultured and maintained in culture bottles according to Valladares et al (2021) .…”

Section: Methodsmentioning

confidence: 99%

Immunoexpression of stem cell markers SOX-2, NANOG AND OCT4 in ameloblastoma

Balbinot

Loureiro

Chemelo

et al. 2023

PeerJ

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Background Ameloblastoma (AME) is characterized by a locally invasive growth pattern. In an attempt to justify the aggressiveness of neoplasms, the investigation of the role of stem cells has gained prominence. The SOX-2, NANOG and OCT4 proteins are important stem cell biomarkers. Methodology To verify the expression of these proteins in tissue samples of AME, dentigerous cyst (DC) and dental follicle (DF), immunohistochemistry was performed and indirect immunofluorescence were performed on the human AME (AME-hTERT) cell line. Results Revealed expression of SOX-2, NANOG and OCT4 in the tissue samples and AME-hTERT lineage. Greater immunostaining of the studied proteins was observed in AME compared to DC and DF (p < 0.001). Conclusions The presence of biomarkers indicates a probable role of stem cells in the genesis and progression of AME.

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HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma

Cited by 10 publications

References 33 publications

α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway

α‑hederin overcomes hypoxia‑mediated drug resistance in colorectal cancer by inhibiting the AKT/Bcl2 pathway

Cell proliferation and apoptosis immunolocalisation suggest an association between aggressiveness and the preferred location of mural unicystic ameloblastomas: A multicentricStudy

Immunoexpression of stem cell markers SOX-2, NANOG AND OCT4 in ameloblastoma

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