Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells

Mansour, Mohammed; Ibrahim, Wafaa; Shalaan, Eman S.; Salama, Afrah F.

doi:10.1002/jbt.22350

Cited by 6 publications

(3 citation statements)

References 26 publications

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“…A link between cisplatin resistance and HK2 expression has been observed in ovarian [82] and cervical [83] cancer models. Cisplatin was able to induce autophagic cell death and inhibit HK2 activity in a cisplatin-sensitive murine mammary adenocarcinoma model [84]. In our study, HK2 positivity clearly separated a group of patients with shorter disease-free and overall survival from those who received cisplatin-based chemotherapy.…”

Section: Discussionsupporting

confidence: 51%

Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy

Afonso

Gonçalves

Costa

et al. 2023

Cancers

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Proliferating cancer cells are able to reprogram their energy metabolism, favouring glycolysis even in the presence of oxygen and fully functioning mitochondria. Research is needed to validate the glycolysis-related proteins as prognostic/predictive biomarkers in urothelial bladder carcinoma (UBC), a malignancy tagged by high recurrence rates and poor response to chemotherapy. Here, we assessed GLUT1, HK2, PFKL, PKM2, phospho-PDH, and LDHA immunoexpression in 76 UBC samples, differentiating among urothelial, fibroblast, and endothelial cells and among normoxic versus hypoxic areas. We additionally studied the functional effects of the HK2 inhibitor 2-deoxy-D-glucose (2DG) in “in vitro” and “in vivo” preclinical UBC models. We showed that the expression of the glycolysis-related proteins is associated with UBC aggressiveness and poor prognosis. HK2 remained as an independent prognostic factor for disease-free and overall survival. 2DG decreased the UBC cell’s viability, proliferation, migration, and invasion; the inhibition of cell cycle progression and apoptosis occurrence was also verified. A significant reduction in tumour growth and blood vessel formation upon 2DG treatment was observed in the chick chorioallantoic membrane assay. 2DG potentiated the cisplatin-induced inhibition of cell viability in a cisplatin-resistant subline. This study highlights HK2 as a prognostic biomarker for UBC patients and demonstrates the potential benefits of using 2DG as a glycolysis inhibitor. Future studies should focus on integrating 2DG into chemotherapy design, as an attempt to overcome cisplatin resistance.

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Section: Discussionsupporting

confidence: 51%

Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy

Afonso

Gonçalves

Costa

et al. 2023

Cancers

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“…Moreover, autophagy activation plays a role in chemo and/or radiation resistance. Autophagy inhibition in tumor cells has been found to enhance the potential of anticancer agents [16,17]. In the present study, we performed a comprehensive molecular docking study to select novel LDH inhibitors that can be utilized in combination with the chemotherapeutic drug cisplatin (CIS) to improve its therapeutic efficiency and decrease associated adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Ethoxyquin Inhibits the Progression of Murine Ehrlich Ascites Carcinoma through the Inhibition of Autophagy and LDH

et al. 2021

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Cancer cells exhibit an increased glycolysis rate for ATP generation (the Warburg effect) to sustain an increased proliferation rate. In tumor cells, the oxidation of pyruvate in the Krebs cycle is substituted by lactate production, catalyzed by LDH. In this study, we use ethoxyquin (EQ) as a novel inhibitor to target LDH in murine Ehrlich ascites carcinoma (EAC) and as a combination therapy to improve the therapeutic efficacy of the conventional chemotherapy drug, cisplatin (CIS). We investigated the anti-tumor effect of EQ on EAC-bearing mice and checked whether EQ can sustain the anti-tumor potential of CIS and whether it influences LDH activity. Treatment with EQ had evident anti-tumor effects on EAC as revealed by the remarkable decrease in the expression of the anti-apoptotic gene Bcl-2 and by a significant increase in the expression of apoptotic genes (BAX and caspase-3). EQ also caused a significant decrease in the autophagic activity of EAC cells, as shown by a reduction in the fluorescence intensity of the autophagosome marker. Additionally, EQ restored the altered hematological and biochemical parameters and improved the disrupted hepatic tissues of EAC-bearing mice. Co-administration of EQ and CIS showed the highest anti-tumor effect against EAC. Collectively, our findings propose EQ as a novel inhibitor of LDH in cancer cells and as a combinatory drug to increase the efficacy of cisplatin. Further studies are required to validate this therapeutic strategy in different cancer models and preclinical trials.

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“…Substâncias com potencial efeito antitumoral devem promover redução da viabilidade celular por meio de apoptose ou estase do ciclo celular (LISBOA et al, 2020;MANSOUR et al, 2019;NISHITANI;LYGEROU, 2002). No presente estudo, tanto a morfina quanto a metadona promoveram maior proporção de células na fase G0/G1 do ciclo celular, o que representa estase no ciclo para que as células tenham tempo para reparar danos em seu DNA ou entrar em apoptose (NISHITANI;LYGEROU, 2002).…”

Section: Discussionunclassified

Efeitos da morfina e metadona sobre o comportamento e crescimento tumoral de camundongos com tumor de Ehrlich

Rusch¹

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À Deus, pela vida, pela oportunidade, pela saúde e por ter colocado pessoas tão especiais na minha vida. Que Ele continue nos abençoando.Aos meus pais, que mesmo sabendo da distância e da dificuldade de ficar longe, apoiaram a ideia da realização desse trabalho até o fim. Agradeço de coração pelo amor incondicional, pelo apoio em todas as horas, mesmo que em algumas fossem vocês quem precisassem... À minha família, vó Elvira, vô Arcelino, Luana, Sadi, Geni, aos tios. Obrigada pelo apoio incondicional. Aos mestres. Ao Doutor Adriano Carregaro que aceitou essa empreitada de orientação e que mesmo de longe fez o melhor que pôde para que o trabalho fosse executado. Sua orientação e disponibilidade foram fundamentais para a elaboração desse projeto. Obrigada pela sua extrema atenção, dedicação, paciência, senso crítico, amizade e confiança ao longo desses anos. Sou eternamente grata pela oportunidade de ter sido sua orientada. Você é e sempre será um grande exemplo para mim.Ao Doutor Heidge Fukumasu pela ajuda em todos os momentos, desde a consolidação da ideia, até a execução do trabalho. Obrigada também pelos conselhos.Ao Rogian pelo companheirismo. Obrigada por ter me acompanhado nessa jornada.A minha amiga Patricia, que me acompanhou durante toda a jornada. A Marilia e Pedro pelo companheirismo pessoal e profissional, pelos churrascos, pipocas, anestesias a campo e experimentos, o apoio de vocês foi incondicional. A Milena, pela ajuda, apoio e amizade desde o tempo do estágio até o experimento do mestrado. Obrigada de coração. Ao Jeff, pelos conselhos, pelas enzimas, pelos cafés da tarde e por toda a ajuda sempre. Mariana Sanches pelas viagens, anestesias e ensinamentos. A Thais pelos conselhos, almoços e companheirismo ao longo desses anos. A Nathalia pelos cafés da manhã e da tarde que ficarão para sempre em meu coração. A Bruna, pela paciência desde o estágio, tenho uma enorme admiração por você. Aos queridos Amanda,

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Combination of arsenic trioxide and cisplatin synergistically inhibits both hexokinase activity and viability of Ehrlich ascites carcinoma cells

Cited by 6 publications

References 26 publications

Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy

Glucose Metabolism Reprogramming in Bladder Cancer: Hexokinase 2 (HK2) as Prognostic Biomarker and Target for Bladder Cancer Therapy

Ethoxyquin Inhibits the Progression of Murine Ehrlich Ascites Carcinoma through the Inhibition of Autophagy and LDH

Efeitos da morfina e metadona sobre o comportamento e crescimento tumoral de camundongos com tumor de Ehrlich

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