Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism

Shoshan, Maria C.

doi:10.2174/1389201011314030007

Cited by 7 publications

(6 citation statements)

References 158 publications

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“…In recent years, new cancer treatment strategies that target the metabolism of cancer cells have emerged [Zhao et al, 2013]. In particular, inhibitors of glycolysis attracted attention as potential anti-MDR agents due to the frequently observed glycolytic phenotype of cancer cells [Kaplan et al, 1990;Shoshan, 2013]. At the same time, our data suggest that specific targeting of highly drug-resistant cells (HDECC) may require inhibition of OXPHOS energetic support of MDR.…”

Section: Discussionmentioning

confidence: 74%

Metabolic Suppression of a Drug‐Resistant Subpopulation in Cancer Spheroid Cells

Koshkin

Ailles

Liu³

et al. 2015

J of Cellular Biochemistry

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Inhibition of metabolic features which distinguish cancer cells from their non-malignant counterparts is a promising approach to cancer treatment. Energy support for drug extrusion in multidrug resistance (MDR) is a potential target for metabolic inhibition. Two major sources of ATP-based metabolic energy are partial (glycolysis) and complete (mitochondrial oxidative phosphorylation) oxidation of metabolic fuels. In cancer cells, the balance between them tends to be shifted toward glycolysis; this shift is considered to be characteristic of the cancer metabolic phenotype. Numerous earlier studies, conducted with cells cultured in a monolayer (2-D model), suggested inhibition of glycolytic ATP production as an efficient tool to suppress MDR in cancer cells. Yet, more recent work challenged the appropriateness of the 2-D model for such studies and suggested that a more clinically relevant approach would utilize a more advanced cellular model such as a 3-D model. Here, we show that the transition from the 2-D model (cultured monolayer) to a 3-D model (cultured spheroids) introduces essential changes into the concept of energetic suppression of MDR. The 3-D cell organization leads to the formation of a discrete cell subpopulation (not formed in the 2-D model) with elevated MDR transport capacity. This subpopulation has a specific metabolic phenotype (mixed glycolytic/oxidative MDR support) different from that of cells cultured in the 2-D model. Finally, the shift to the oxidative phenotype becomes greater when the spheroids are grown under conditions of lactic acidosis that are typical for solid tumors. The potential clinical significance of these findings is discussed.

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Section: Discussionmentioning

confidence: 74%

Metabolic Suppression of a Drug‐Resistant Subpopulation in Cancer Spheroid Cells

Koshkin

Ailles

Liu³

et al. 2015

J of Cellular Biochemistry

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“…There is a growing body of literature demonstrating that an increased sodium concentration is a common feature observed in many tumor types . This fact is correlated with the known observations that tumor cells have upregulated cellular energy metabolism and, furthermore, its modulation can potentiate cancer therapy . Further evidence is now available that mitochondria play a key role in both ATP production and apoptosis.…”

Section: Sodium Mri and The Prediction Of Tumor Resistance Prior To Tmentioning

confidence: 72%

Sodium MRI of glioma in animal models at ultrahigh magnetic fields

Schepkin

2015

NMR in Biomedicine

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High magnetic fields expand our capability to use sodium MRI for biomedical applications. The central goal of this review is devoted to the unique features of sodium MRI in tumor animal models, mainly in glioma, performed at 9.4 and 21.1 T. The ability of sodium MRI to monitor tumor response to therapy was evaluated. It is noteworthy that sodium MRI can detect glioma response to chemotherapy earlier than diffusion MRI. Especially attractive is the ability of sodium MRI to predict tumor therapeutic resistance before therapy. The non-invasive prediction of tumor chemo-resistance by sodium MRI presents a potential to individualize strategies for cancer treatment. Specifics of sodium MRI and technical aspects of imaging are also presented.

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“…Bitter melon has been suspected to utilize the second strategy and our results suggest the same. Some energy modulators as well as calorie control in cancer patients have been shown to have positive effect on tumor progression [37]. Upon treatment of colon cancer cells with increasing concentration of bitter melon flesh extracts, there was a marked decrease in ATP production.…”

Section: Discussionmentioning

confidence: 99%

Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

Kwatra

Subramaniam

Ramamoorthy

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Bitter melon fruit is recommended in ancient Indian and Chinese medicine for prevention/treatment of diabetes. However its effects on cancer progression are not well understood. Here, we have determined the efficacy of methanolic extracts of bitter melon on colon cancer stem and progenitor cells. Both, whole fruit (BMW) and skin (BMSk) extracts showed significant inhibition of cell proliferation and colony formation, with BMW showing greater efficacy. In addition, the cells were arrested at the S phase of cell cycle. Moreover, BMW induced the cleavage of LC3B but not caspase 3/7, suggesting that the cells were undergoing autophagy and not apoptosis. Further confirmation of autophagy was obtained when western blots showed reduced Bcl-2 and increased Beclin-1, Atg 7 and 12 upon BMW treatment. BMW reduced cellular ATP levels coupled with activation of AMP activated protein kinase; on the other hand, exogenous additions of ATP lead to revival of cell proliferation. Finally, BMW treatment results in a dose-dependent reduction in the number and size of colonospheres. The extracts also decreased the expression of DCLK1 and Lgr5, markers of quiescent, and activated stem cells. Taken together, these results suggest that the extracts of bitter melon can be an effective preventive/therapeutic agent for colon cancer.

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Potentiation of Anti-Cancer Treatment by Modulators of Energy Metabolism

Cited by 7 publications

References 158 publications

Metabolic Suppression of a Drug‐Resistant Subpopulation in Cancer Spheroid Cells

Metabolic Suppression of a Drug‐Resistant Subpopulation in Cancer Spheroid Cells

Sodium MRI of glioma in animal models at ultrahigh magnetic fields

Methanolic Extracts of Bitter Melon Inhibit Colon Cancer Stem Cells by Affecting Energy Homeostasis and Autophagy

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