PK-M2-mediated metabolic changes in breast cancer cells induced by ionizing radiation

Zhang, Le; Bailleul, Justine; Yazal, Taha; Dong, Kevin; Sung, David; Dao, Amy; Gosa, Laura; Nathanson, David; Bhat, Kruttika; Duhachek-Muggy, Sara; Alli, Claudia; Dratver, Milana Bochkur; Pajonk, Frank; Vlashi, Erina

doi:10.1007/s10549-019-05376-9

Cited by 13 publications

(16 citation statements)

References 57 publications

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“…Moreover, alteration in metabolism by metformin may have increased the radiation‐mediated anticancer effects. A recently published paper supports our results that the triple‐negative breast cancer cells, MDA‐MB‐231 and SUM159PT, on treatment with 8 Gy radiation, showed increased glucose uptake and lactate production, suggesting that the re‐wiring of glucose metabolism may be necessary for cell survival and resistance to radiation 27 . Interestingly, we found that the treatment with adjuvant metformin and 10 Gy radiation increased the glucose uptake, but the degree of glucose uptake was less than that observed after treatment with radiation alone.…”

Section: Discussionsupporting

confidence: 87%

“…2.12 | 2-NDBG glucose uptake Glucose uptake was measured using a 2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose (2-NBDG) glucose uptake assay kit (K682, BioVision) following a previous report. 27 MDA-MB-231(BR)-Luc cells were seeded in a 6 cm dish at a density of 2 Â 10 5 cells. Cells were treated with 5 mM metformin for 4 h, exposed to 10 Gy X-rays, and harvested after 24 h using trypsin-EDTA.…”

Section: Lactate Measurementmentioning

confidence: 99%

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Offset of apparent hyperpolarized ¹³C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

Choi

Lee

et al. 2021

NMR in Biomedicine

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An increase in hyperpolarized (HP) [1‐13C]lactate production has been suggested as a biomarker for cancer occurrence as well as for response monitoring of cancer treatment. Recently, the use of metformin has been suggested as an anticancer or adjuvant treatment. By regulating the cytosolic NAD+/NADH redox state, metformin stimulates lactate production and increases the HP [1‐13C]lactate conversion rate in the kidney, liver, and heart. In general, increased HP [1‐13C]lactate is regarded as a sign of cancer occurrence or tumor growth. Thus, the relationship between the tumor suppression effect of metformin and the change in metabolism monitored by HP [1‐13C]pyruvate MRS in cancer treatment needs to be investigated. The present study was performed using a brain metastasis animal model with MDA‐MB‐231(BR)‐Luc breast cancer cells. HP [1‐13C]pyruvate MRS, T2‐weighted MRI, and bioluminescence imaging were performed in groups treated with metformin or adjuvant metformin and radiation therapy. Metformin treatment alone did not display a tumor suppression effect, and the HP [1‐13C]lactate conversion rate increased. In radiation therapy, the HP [1‐13C]lactate conversion rate decreased with tumor suppression, with a p‐value of 0.028. In the adjuvant metformin and radiation treatment, the tumor suppression effect increased, with a p‐value of 0.001. However, the apparent HP [1‐13C]lactate conversion rate (Kpl) was observed to be offset by two opposite effects: a decrease on radiation therapy and an increase caused by metformin treatment. Although HP [1‐13C]pyruvate MRS could not evaluate the tumor suppression effect of adjuvant metformin and radiation therapy due to the offset phenomenon, metabolic changes following only metformin pre‐treatment could be monitored. Therefore, our results indicate that the interpretation of HP [1‐13C]pyruvate MRS for response monitoring of cancer treatment should be carried out with caution when metformin is used as an adjuvant cancer therapy.

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Section: Discussionsupporting

confidence: 87%

Section: Lactate Measurementmentioning

confidence: 99%

Offset of apparent hyperpolarized ¹³C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

Choi

Lee

et al. 2021

NMR in Biomedicine

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“…Although inhibition of hormone receptors, DNA damage repair, and immunomodulatory signaling represent the majority of the approaches to radiosensitization currently being studied in the clinic (Table 1), there are a number of other emerging preclinical radiosensitization strategies ( Abbreviations: DNAPK, DNA-dependent protein kinase; dsDNA, double-strand DNA; EGFR, epidermal growth factor receptor; ER, estrogen receptor; ERK, extracellular regulated kinase; HER2, human epidermal growth factor receptor 2; HR, homologous recombination; mTOR, mammalian target of rapamycin; TNBC, triple-negative breast cancer, VEGF, vascular endothelial growth factor. autophagy in, [149][150][151][152][153][154][155][156] or metabolic changes 157,158 usually thought to be minor contributing pathways to breast cancer radiosensitization, a number of these approaches likely have mixed mechanisms that lead to broad suppression of the DNA damage response, cell-cycle progression, or decreased hypoxia and HIF1a-related signaling. 127,[159][160][161][162][163][164][165][166][167] On-target and off-target effects of compounds designed to affect proliferation or cell-cell communication, such as the suppression of notch signaling 168 through gamma secretase inhibition 169 (Clinical-Trials.gov identifier: NCT01217411), can also be valuable approaches in the radiosensitization of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Modulating the Radiation Response for Improved Outcomes in Breast Cancer

Pesch

Pierce

Speers

2021

JCO Precision Oncology

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“…The PGs ( n = 30) were collected from 2-day old females and then incubated in Graces' medium for 2 h. The medium was replaced by a new medium with PBAN (10 pM). PGs were collected at different time points of PBAN treatments (0, 10, 30, 60, and 90 min) and subjected to HaPYK activity analysis using the PYK activity kit from the Abcam company (Abcam, Cambridge, UK) following the instructions (Zhang et al, 2019 ). Three biological replicates were employed and every replicate contained at least 30 PGs.…”

Section: Methodsmentioning

confidence: 99%

Pyruvate Kinase Is Required for Sex Pheromone Biosynthesis in Helicoverpa armigera

et al. 2021

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Pyruvate kinase (PYK) is a speed-limited enzyme of glycolysis that catalyzes the formation of pyruvate, and plays an important role in acetyl-CoA synthesis. The acetyl-CoA is the precursor of sex pheromone biosynthesis in Helicoverpa armigera. However, the role of PYK in sex pheromone biosynthesis remains elusive. Here, PYK in H. armigera (HaPYK) was found to be highly expressed in the pheromone glands (PGs). The developmental expression profile of HaPYK was consistent with the fluctuation of sex pheromone release. Function analysis revealed that the knockdown of HaPYK led to a decrease in the levels of pyruvic acid and acetyl-CoA in PGs, which in turn caused a significant decrease in cis-11-hexadecenal (Z11-16: Ald) production, female capability to attract males, and mating frequency. Further study demonstrated that sugar feeding (5% sugar) increased the transcription and enzyme activity of HaPYK, thereby facilitating sex pheromone biosynthesis. Moreover, pheromone biosynthesis activating neuropeptide (PBAN) upregulated HaPYK activity through protein kinase C (PKC), as shown by PKC-specific inhibitor analysis. Altogether, our results revealed that PBAN activated HaPYK by Ca2+/PKC, thereby regulating the synthesis of pyruvate and subsequent acetyl-CoA, ensuring the supply of sex pheromone precursor, and finally facilitating sex pheromone biosynthesis and mating behavior.

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PK-M2-mediated metabolic changes in breast cancer cells induced by ionizing radiation

Cited by 13 publications

References 57 publications

Offset of apparent hyperpolarized ¹³C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

Offset of apparent hyperpolarized ¹³C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

Modulating the Radiation Response for Improved Outcomes in Breast Cancer

Pyruvate Kinase Is Required for Sex Pheromone Biosynthesis in Helicoverpa armigera

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PK-M2-mediated metabolic changes in breast cancer cells induced by ionizing radiation

Cited by 13 publications

References 57 publications

Offset of apparent hyperpolarized 13C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

Offset of apparent hyperpolarized 13C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

Modulating the Radiation Response for Improved Outcomes in Breast Cancer

Pyruvate Kinase Is Required for Sex Pheromone Biosynthesis in Helicoverpa armigera

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Offset of apparent hyperpolarized ¹³C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo

Offset of apparent hyperpolarized ¹³C lactate flux by the use of adjuvant metformin in ionizing radiation therapy in vivo