Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide

Agrawal, Siddarth; Łuc, Mateusz; Ziółkowski, Piotr; Agrawal, Anil Kumar; Pielka, Ewa; Walaszek, K; Zduniak, Krzysztof; Woźniak, Marta

doi:10.1177/1010428317702901

Cited by 12 publications

(18 citation statements)

References 39 publications

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“…Indeed, it regulates carbohydrate and lipid metabolism, stimulates DNA synthesis, modulates transcription [118], and stimulates the cellular uptake of various nutrients, including glucose, by facilitated diffusion [119]. Agrawal et al studied the effect of insulin on the sensitivity of a breast cancer cell line (MCF-7) to 5-fluorouracil (5FU) and cyclophosphamide (CPA) [120]. The chemotherapeutic agents 5FU and CPA are widely used in the clinic and incorporated in the treatment of several cancer, including breast cancer, being associated with increased levels of chemoresistance.…”

Section: Insulinmentioning

confidence: 99%

“…This effect of insulin was linked to enhancement of apoptosis, activation of apoptotic and autophagic pathways, and to overexpression of GLUT1 and GLUT3 as well as to inhibition of cell proliferation and motility (Table 2). Therefore, it was concluded that insulin sensitization before chemotherapy treatment could overcome chemoresistance [120]. The effect of insulin upon GLUT1 and GLUT3 protein expression levels were hypothesized to be mediated by the PI3K-Akt pathway, but the hypothesis was not tested.…”

Section: Insulinmentioning

confidence: 99%

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Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Barbosa

Martel

2020

Cancers

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Reprogramming of cellular energy metabolism is widely accepted to be a cancer hallmark. The deviant energetic metabolism of cancer cells-known as the Warburg effect-consists in much higher rates of glucose uptake and glycolytic oxidation coupled with the production of lactic acid, even in the presence of oxygen. Consequently, cancer cells have higher glucose needs and thus display a higher sensitivity to glucose deprivation-induced death than normal cells. So, inhibitors of glucose uptake are potential therapeutic targets in cancer. Breast cancer is the most commonly diagnosed cancer and a leading cause of cancer death in women worldwide. Overexpression of facilitative glucose transporters (GLUT), mainly GLUT1, in breast cancer cells is firmly established, and the consequences of GLUT inhibition and/or knockout are under investigation. Herein we review the compounds, both of natural and synthetic origin, found to interfere with uptake of glucose by breast cancer cells, and the consequences of interference with that mechanism on breast cancer cell biology. We will also present data where the interaction with GLUT is exploited in order to increase the efficiency or selectivity of anticancer agents, in breast cancer cells.

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Section: Insulinmentioning

confidence: 99%

Section: Insulinmentioning

confidence: 99%

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Barbosa

Martel

2020

Cancers

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“…Insulin has the ability to enhance the cytotoxic effect of chemotherapy in vitro ( 43 ), which may explain the observed decreased recurrence-risk among overweight or obese chemotherapy-treated patients with nuclear InsR + tumors in this study. The interplay between InsR, ER and IGF1R emphasizes the importance of combining the expression of nuclear InsR and ER and their impact as prognostic and treatment predictive biomarkers needs further elucidation.…”

Section: Discussionmentioning

confidence: 66%

Body Mass Index Influences the Prognostic Impact of Combined Nuclear Insulin Receptor and Estrogen Receptor Expression in Primary Breast Cancer

et al. 2017

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The prognostic importance of tumor-specific nuclear insulin receptor (InsR) expression in breast cancer is unclear, while membrane and cytoplasmic localization of InsR is better characterized. The insulin signaling network is influenced by obesity and may interact with the estrogen receptor α (ERα) signaling. The purpose was to investigate the interplay between nuclear InsR, ER, body mass index (BMI), and prognosis. Tumor-specific expression of nuclear InsR was evaluated by immunohistochemistry in tissue microarrays from 900 patients with primary invasive breast cancer without preoperative treatment, included in a population-based cohort in Sweden (2002–2012) in relation to prognosis. Patients were followed for up to 11 years during which 107 recurrences were observed. Nuclear InsR+ expression was present in 214 patients (23.8%) and increased with longer time between surgery and staining (P < 0.001). There were significant effect modifications by ER status and BMI in relation to clinical outcomes. Nuclear InsR+ conferred higher recurrence-risk in patients with ER+ tumors, but lower risk in patients with ER− tumors (Pinteraction = 0.003). Normal-weight patients with nuclear InsR+ tumors had higher recurrence-risk, while overweight or obese patients had half the recurrence-risk compared to patients with nuclear InsR− tumors (Pinteraction = 0.007). Normal-weight patients with a nuclear InsR−/ER+ tumor had the lowest risk for recurrence compared to all other nuclear InsR/ER combinations [HRadj 0.50, 95% confidence interval (CI): 0.25–0.97], while overweight or obese patients with nuclear InsR−/ER− tumors had the worst prognosis (HRadj 7.75, 95% CI: 2.04–29.48). Nuclear InsR was more prognostic than ER among chemotherapy-treated patients. In summary, nuclear InsR may have prognostic impact among normal-weight patients with ER+ tumors and in overweight or obese patients with ER− tumors. Normal-weight patients with nuclear InsR−/ER+ tumors may benefit from less treatment than normal-weight patients with other nuclear InsR/ER combinations. Overweight or obese patients with nuclear InsR−/ER− tumors may benefit from more tailored treatment or weight management.

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“…Due to its complex influence on malignant cell metabolism, insulin has been exploited as a potential sensitizing agent in cancer therapy. Several in vitro and clinical studies have found that the inhibitory effect of various cytotoxic agents can be enhanced in the presence of insulin [ 21 – 25 ].…”

Section: Discussionmentioning

confidence: 99%

“…Its impact on cellular uptake of many compounds including glucose by facilitated diffusion has been documented [ 20 ]. The use of insulin for cancer-specific treatment has been tested in several studies [ 21 – 25 ].…”

Section: Introductionmentioning

confidence: 99%

Insulin and novel thioglycosides exert suppressive effect on human breast and colon carcinoma cells

et al. 2017

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The rationale for the implementation of novel therapies should be based on hallmarks of cancer. Two novel compounds labelled as thioglycoside A and B were designed and evaluated on breast and colon cancer cell lines. We assessed their cytotoxic effect after sensitizing cancer cells with insulin. In order to explore the underlying mechanisms, we performed tests to assess cell migration and motility, apoptosis, expression of glucose transporter 1 and proapoptotic proteins. Both compounds proved to have an antitumor effect which was significantly enhanced in combination with insulin. Linking glucose and anticancer agent presents an approach that exploits the Warburg effect. Targeting dysfunctional glycometabolism and increased glucose absorption is emerging as a promising anticancer strategy.

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Insulin-induced enhancement of MCF-7 breast cancer cell response to 5-fluorouracil and cyclophosphamide

Cited by 12 publications

References 39 publications

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Targeting Glucose Transporters for Breast Cancer Therapy: The Effect of Natural and Synthetic Compounds

Body Mass Index Influences the Prognostic Impact of Combined Nuclear Insulin Receptor and Estrogen Receptor Expression in Primary Breast Cancer

Insulin and novel thioglycosides exert suppressive effect on human breast and colon carcinoma cells

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