Potential Therapeutic Targets in Energy Metabolism Pathways of Breast Cancer

Islam, Rowshan Ara; Hossain, Sorif; Chowdhury, Ezharul Hoque

doi:10.2174/1568009617666170330150458

Cited by 24 publications

(20 citation statements)

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“…Cancer cells undergo the Warburg effect, a shift in metabolic behavior away from mitochondrial oxidative phosphorylation (OXPHOS), towards aerobic glycolysis (GLY), even in the presence of excess oxygen [25]. Therefore, it has been of great interest to target the mitochondrial function as well as energy-related metabolic pathways for therapeutic development [26]. Cisplatin, a well-known platinum-based chemotherapeutic drug, is widely used as one of the major therapeutic options against cancer due to its ability to activate the DNA damage response and the induction of mitochondrial apoptosis exerts.…”

Section: Introductionmentioning

confidence: 99%

Caffeine and Cisplatin Effectively Targets the Metabolism of a Triple-Negative Breast Cancer Cell Line Assessed via Phasor-FLIM

Pascua

McGahey

et al. 2020

IJMS

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Triple-negative tumor cells, a malignant subtype of breast cancer, lack a biologically targeted therapy. Given its DNA repair inhibiting properties, caffeine has been shown to enhance the effectiveness of specific tumor chemotherapies. In this work, we have investigated the effects of caffeine, cisplatin, and a combination of the two as potential treatments in energy metabolism for three cell lines, triple-negative breast cancer (MDA-MB-231), estrogen-receptor lacking breast cancer (MCF7) and breast epithelial cells (MCF10A) using a sensitive label-free approach, phasor-fluorescence lifetime imaging microscopy (phasor-FLIM). We found that solely using caffeine to treat MDA-MB-231 shifts their metabolism towards respiratory-chain phosphorylation with a lower ratio of free to bound NADH, and a similar trend is seen in MCF7. However, MDA-MB-231 cells shifted to a higher ratio of free to bound NADH when cisplatin was added. The combination of cisplatin and caffeine together reduced the survival rate for MDA-MD231 and shifted their energy metabolism to a higher fraction of bound NADH indicative of oxidative phosphorylation. The FLIM and viability results of MCF10A cells demonstrate that the treatments targeted cancer cells over the normal breast tissue. The identification of energy metabolism alteration could open up strategies of improving chemotherapy for malignant breast cancer.

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Section: Introductionmentioning

confidence: 99%

Caffeine and Cisplatin Effectively Targets the Metabolism of a Triple-Negative Breast Cancer Cell Line Assessed via Phasor-FLIM

Pascua

McGahey

et al. 2020

IJMS

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“…We additionally included the ratios of (Ser/C2, Ser/Gln, Ser/Thr) and of (PC aa C42:0/PC ae C32:3, PC aa C32:2/PC ae C34:2) as proxies for glycolysis-related phosphoglycerate dehydrogenase (PHGDH) and glucokinase regulator (GCKR) activities [ 6 – 7 ].…”

Section: Methodsmentioning

confidence: 99%

“…Many oncogenes are now known to regulate metabolic pathways that are critical for cell survival in the inhospitable tumor micro-environment, where oxygen and nutrient sources are highly limited. Indeed RAS, PI3K, TP53 and MYC among others are now recognized to be important metabolic regulators whose functions are fundamental for tumor cell survival [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality

et al. 2018

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Breast cancer remains a leading cause of morbidity and mortality worldwide yet methods for early detection remain elusive. We describe the discovery and validation of biochemical signatures measured by mass spectrometry, performed upon blood samples from patients and controls that accurately identify (>95%) the presence of clinical breast cancer. Targeted quantitative MS/MS conducted upon 1225 individuals, including patients with breast and other cancers, normal controls as well as individuals with a variety of metabolic disorders provide a biochemical phenotype that accurately identifies the presence of breast cancer and predicts response and survival following the administration of neoadjuvant chemotherapy. The metabolic changes identified are consistent with inborn-like errors of metabolism and define a continuum from normal controls to elevated risk to invasive breast cancer. Similar results were observed in other adenocarcinomas but were not found in squamous cell cancers or hematologic neoplasms. The findings describe a new early detection platform for breast cancer and support a role for pre-existing, inborn-like errors of metabolism in the process of breast carcinogenesis that may also extend to other glandular malignancies.Statement of Significance: Findings provide a powerful tool for early detection and the assessment of prognosis in breast cancer and define a novel concept of breast carcinogenesis that characterizes malignant transformation as the clinical manifestation of underlying metabolic insufficiencies.

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“…Increasing evidence supports the notion that dysregulated metabolism confers drug resistance and recurrence in breast cancer [ 156 ]. Breast cancer cells, like most cancer cells, use glucose and glutamine to survive, so, conceptually, targeting the energy-related metabolic pathways for therapeutic intervention in breast cancer is an exciting idea [ 183 ]. However, there is a fine balance between p53 regulation of mitochondrial processes, cell death, or cell survival in normal and cancer tissues.…”

Section: P53 and Breast Cancer Metabolismmentioning

confidence: 99%

The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer?

Moulder

Hatoum

Tay

et al. 2018

Cancers

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Cancer research has been heavily geared towards genomic events in the development and progression of cancer. In contrast, metabolic regulation, such as aberrant metabolism in cancer, is poorly understood. Alteration in cellular metabolism was once regarded simply as a consequence of cancer rather than as playing a primary role in cancer promotion and maintenance. Resurgence of cancer metabolism research has identified critical metabolic reprogramming events within biosynthetic and bioenergetic pathways needed to fulfill the requirements of cancer cell growth and maintenance. The tumor suppressor protein p53 is emerging as a key regulator of metabolic processes and metabolic reprogramming in cancer cells—balancing the pendulum between cell death and survival. This review provides an overview of the classical and emerging non-classical tumor suppressor roles of p53 in regulating mitochondrial dynamics: mitochondrial engagement in cell death processes in the prevention of cancer. On the other hand, we discuss p53 as a key metabolic switch in cellular function and survival. The focus is then on the conceivable roles of p53 in breast cancer metabolism. Understanding the metabolic functions of p53 within breast cancer metabolism will, in due course, reveal critical metabolic hotspots that cancers advantageously re-engineer for sustenance. Illustration of these events will pave the way for finding novel therapeutics that target cancer metabolism and serve to overcome the breast cancer burden.

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Potential Therapeutic Targets in Energy Metabolism Pathways of Breast Cancer

Cited by 24 publications

References 0 publications

Caffeine and Cisplatin Effectively Targets the Metabolism of a Triple-Negative Breast Cancer Cell Line Assessed via Phasor-FLIM

Caffeine and Cisplatin Effectively Targets the Metabolism of a Triple-Negative Breast Cancer Cell Line Assessed via Phasor-FLIM

Inborn-like errors of metabolism are determinants of breast cancer risk, clinical response and survival: a study of human biochemical individuality

The Roles of p53 in Mitochondrial Dynamics and Cancer Metabolism: The Pendulum between Survival and Death in Breast Cancer?

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