Narrow Results

Most cancer cells predominantly produce ATP by maintaining a high rate of lactate fermentation, rather than by maintaining a comparatively low rate of tricarboxylic acid cycle, i.e., Warburg’s effect. In the pathway, the pyruvate produced by glycolysis is converted to lactic acid by lactate dehydrogenase (LDH). Here, we demonstrated that water extracts from the seeds of Myristica fragrans Houtt. (MF) inhibit the in vitro enzymatic activity of LDH. MF effectively suppressed cell growth and the overall Warburg effect in HT29 human colon cancer cells. Although the expression of LDH-A was not changed by MF, both lactate production and LDH activity were decreased in MF-treated cells under both normoxic and hypoxic conditions. In addition, intracellular ATP levels were also decreased by MF treatment, and the uptake of glucose was also reduced by MF treatment. Furthermore, the experiment on tumor growth in the in vivo mice model revealed that MF effectively reduced the growth of allotransplanted Lewis lung carcinoma cells. Taken together, these results suggest that MF effectively inhibits cancer growth and metabolism by inhibiting the activity of LDH, a major enzyme responsible for regulating cancer metabolism. These results implicate MF as a potential candidate for development into a novel drug against cancer through inhibition of LDH activity.

The fundamental property of biological systems is a coherent state far from thermodynamic equilibrium excited and sustained by energy supply. Mitochondria in eukaryotic cells produce energy and form conditions for excitation of oscillations in microtubules. Microtubule polar oscillations generate a coherent state far from thermodynamic equilibrium which makes possible cooperation of cells in the tissue. Mitochondrial dysfunction (the Warburg effect) in cancer development breaks down energy of the coherent state far from thermodynamic equilibrium and excludes the afflicted cell from the ordered multicellular tissue system. Cancer lowering of energy and coherence of the state far from thermodynamic equilibrium is the biggest difference from the healthy cells. Cancer treatment should target mitochondrial dysfunction to restore the coherent state far from thermodynamic equilibrium, apoptotic pathway, and subordination of the cell in the tissue. A vast variety of genetic changes and other disturbances in different cancers can result in several triggers of mitochondrial dysfunction. In cancers with the Warburg effect, mitochondrial dysfunction can be treated by inhibition of four isoforms of pyruvate dehydrogenase kinases. Treatment of the reverse Warburg effect cancers would be more complicated. Disturbances of cellular electromagnetic activity by conducting and asbestos fibers present a special problem of treatment.

The early detection of circulating tumor cells (CTCs) in blood as part of medical diagnosis will give the doctors a head start in the provision and treatment of cancer, and therefore, with the advance in Nano technology, there is an increasing expectation of some form of early detection of circulating tumor cells at a highly sensitive level, without any biomarkers, for both early cancer diagnosis and monitoring disease progression after medical intervention. This technical note reports on the recent development in detection of highly sensitive detection of cancer cells without biomarkers. This novel concept is developed based on a hallmark cancer metabolic pattern: high glycolysis rate. Secretion of high level of lactate acid by cancer cells ultimately results in negative electrical charges on their surfaces, enabling strong binding and capturing by the positively-charged nanoprobes, and subsequent magnetic separation. When nanoprobes are incubated with cancer cells in suspension, binding takes place due to charge differences, and cancer cells are then magnetically separated. The separated cells are enumerated using a flow cytometry and identified by pathological and genome sequencing methods. Preliminary results using the approach have shown exceptionally high cancer cell capture rates, therefore potentially applicable in cancer cell detection in clinical settings.

The early detection of circulating tumor cells (CTCs) in blood as part of medical diagnosis will give the doctors a head start in the provision and treatment of cancer, and therefore, with the advance in Nano technology, there is an increasing expectation of some form of early detection of circulating tumor cells at a highly sensitive level, without any biomarkers, for both early cancer diagnosis and monitoring disease progression after medical intervention. This technical note reports on the recent development in detection of highly sensitive detection of cancer cells without biomarkers. This novel concept is developed based on a hallmark cancer metabolic pattern: high glycolysis rate. Secretion of high level of lactate acid by cancer cells ultimately results in negative electrical charges on their surfaces, enabling strong binding and capturing by the positively-charged nanoprobes, and subsequent magnetic separation. When nanoprobes are incubated with cancer cells in suspension, binding takes place due to charge differences, and cancer cells are then magnetically separated. The separated cells are enumerated using a flow cytometry and identified by pathological and genome sequencing methods. Preliminary results using the approach have shown exceptionally high cancer cell capture rates, therefore potentially applicable in cancer cell detection in clinical settings.