Enhanced Radiosensitivity and Chemosensitivity of Breast Cancer Cells by 2-Deoxy-D-Glucose in Combination Therapy

Abstract

Breast cancer is the most common malignancy, and it is also the major cause of cancer-related deaths of women worldwide. Breast cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy, and novel strategies are needed to boost the oncologic outcome. The non-metabolizable glucose analogue, 2-deoxy-D-glucose (2-DG) which inhibits glucose synthesis and adenosine triphosphate production, is one of the important discoveries involving the disturbances that can be caused to the process of the metabolism. The glucose analogue, 2-DG, is known as a tumor sensitizer to irradiation (IR) and chemotherapy, which help improve the treatment rates. It enhances the cytotoxicity via oxidative stress, which is more redundant in tumor cells than in normal ones. This article provides a brief summary on studies related to 2-DG chemo-/radio-sensitization effects by combination therapy of 2-DG/IR or 2-DG/doxorubicin.

High Efficiency Apoptosis Induction in Breast Cancer Cell Lines by MLN4924/2DG Co-Treatment

“…Also, accelerated glucose uptake for aerobic glycolysis is one of the major metabolic changes found in malignant cells. Thus, using the nonmetabolizable glucose analog, 2-deoxy-D-glucose (2DG) interferes with glucose metabolism leading to breast cancer cell death (Zhang and Aft, 2009;Aghaee et al, 2012). 2DG is an inhibitor of glucose metabolism by inhibiting hexokinase that is the first rate-limiting enzyme of glycolysis (Ben Sahra et al, 2010).…”

A study on drug delivery tracing with radiolabeled mesoporous hydroxyapatite nanoparticles conjugated with 2DG/DOX for breast tumor cells

“…Finally, the absorbance was read using an ELISA plate reader (Biotech, Bad Friedrichshall, Germany) at 570 nm wavelength. All the calculated data were analyzed relatively to the untreated cells and then normalized [11].…”

“…The cell lines were cultured in RPMI-1640 media supplemented with 10% heat-inactivated (50°C, 30 minutes) fetal bovine serum (FBS), penicillin (100 U/mL), streptomycin (100 μg/mL), and amphotericin B (0.25 μg/mL) at 5% CO 2 and 95% air in a humidified 37°C incubator [11].…”

“…The combination of 2-deoxy-D-glucose (2DG), structural analogue of glucose, and doxorubicin (DOX), a commonly used anticancer chemodrug, have shown a significant cell toxicity on cells with a rapid dividing capacity (T47D) compared to 2DG or DOX alone [11][12][13]. Also it was found that 2DG and DOX loaded with mesoporous HA could enhance the susceptibility of breast cancer cells to chemotherapy and radiotherapy [2,10].…”

Breast cancer: early diagnosis and effective treatment by drug delivery tracing

“…Therefore, breast cancer is the main reason of cancer-related deaths of women worldwide [1][2][3]. In 2014, an estimated 232,670 new cases of invasive breast cancer were expected to be diagnosed in women in the U.S.; along with 62,570 new cases of non-invasive (in situ) breast cancer.…”