Melatonin in Mitochondria: Mitigating Clear and Present Dangers

(1)A fundamental viewpoint about cancer cellsAt the present time, methods of treatment for cancer base on the viewpoint that cancer cells make humans deaths, therefore a treatment destroys and kills cancer cells and saves patients. But this conception strikes against the limit on treatment. A cancer cell changed from a normal cell of a human, it does not invade from outside and harm a human like virus. A cancer cell is derived from a human cell, therefore when we aim to destroy cancer cells, this attack damages to other normal cells and weaken vital energy of a human. Here there is the limit of treatment for cancer.In opposition to these thoughts, this theory is based on the viewpoint that normal cells faced to critical situation to live and changed its system to survive under the situation and that are certainly cancer cells. The reason why a cancer cell has tough vitality to make a human death is the result to acquire the ability for existing under such a situation. Therefore a treatment for cancer is not to destroy and to kill but to remove factors that prevent normal cells from living orderly. Then cancer cells become unnecessary to derive a tough vitality. And its rapid division and multiplication will stop and return to normal cells.I built the theoretical model as follows. A cell becomes lack of oxygen that is necessary to live. Then hydrogen ions emerge in that cell. Hydrogen ions promote division and multiplication. Take these hydrogen ions out by supplying oxygen like a normal cell doing, and cancer cells will stop division and return to normal cells.This research intends to explain by facts already known and prove this model on,how hydrogen ions emerge in cells?how hydrogen ions promote cell division? Thenhow a treatment for cancer is possible?(2)The division of works of building theoretical models and experiments on biology and medical scienceSome historical discoveries on physics have walked on the process that a theoretical research predicts the existence of materials or the law and some experiments prove it. Physics is divided into two areas. One is theoretical physics that builds theoretical models and another is experimental physics that proves those models by experiments. In medical science and biology, usually one researcher builds a supposition and proves it by experiments. Theoretical work and verification by experimental work are not divided. A theoretical model without experimental proof is not enough recognized its medical or biological value.However more multiple researches will be possible by dividing theoretical work to build theoretical models and experimental work to verify it in the field of cancer that is not solved an ultimate cause and a mechanism to change from normal cells. And it should value theoretical researches that are not yet verified by experiments.This treatise is the theoretical model that is not proved by experiments. I illustrated specific ways for experiments to prove in Chapter 4, “The principle and practical methods of medical treatment for cancer of human beings, (1)Supply oxygen to cultured cancer cells, and multiplication of cancer cells will stop”.I hope that scientists of medical science and biology would prove it by experiments.

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Marine Carotenoid Fucoxanthin Possesses Anti-Metastasis Activity: Molecular Evidence

Marine Drugs ◽

10.3390/md17060338 ◽

2019 ◽

Vol 17 (6) ◽

pp. 338 ◽

Cited By ~ 7

Author(s):

Sukant Garg ◽

Sajal Afzal ◽

Ahmed Elwakeel ◽

Damini Sharma ◽

Navaneethan Radhakrishnan ◽

...

Keyword(s):

Cancer Cells ◽

Human Cancer ◽

Cell Phenotype ◽

Molecular Evidence ◽

Mechanistic Studies ◽

Normal Cells ◽

Therapy Regimen ◽

Molecular Assays ◽

Transcriptional Suppression ◽

P53 Status

Fucoxanthin is commonly found in marine organisms; however, to date, it has been one of the scarcely explored natural compounds. We investigated its activities in human cancer cell culture-based viability, migration, and molecular assays, and found that it possesses strong anticancer and anti-metastatic activities that work irrespective of the p53 status of cancer cells. In our experiments, fucoxanthin caused the transcriptional suppression of mortalin. Cell phenotype-driven molecular analyses on control and treated cells demonstrated that fucoxanthin caused a decrease in hallmark proteins associated with cell proliferation, survival, and the metastatic spread of cancer cells at doses that were relatively safe to the normal cells. The data suggested that the cancer therapy regimen may benefit from the recruitment of fucoxanthin; hence, it warrants further attention for basic mechanistic studies as well as drug development.

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Benzimidazole based Pt(ii) complexes with better normal cell viability than cisplatin: synthesis, substitution behavior, cytotoxicity, DNA binding and DFT study

RSC Advances ◽

10.1039/c6ra17788c ◽

2016 ◽

Vol 6 (80) ◽

pp. 76600-76613 ◽

Cited By ~ 12

Author(s):

Ishani Mitra ◽

Subhajit Mukherjee ◽

Venkata P. Reddy B. ◽

Subrata Dasgupta ◽

Jagadeesh C. Bose K ◽

...

Keyword(s):

Dna Binding ◽

Cell Viability ◽

Cancer Cells ◽

Normal Cell ◽

Water Soluble ◽

Dft Study ◽

Normal Cells

Water soluble Pt(ii) complexes with higher viability towards normal cells and comparable cytotoxicity to cancer cells as compared to cisplatin.

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The Effect of Diopatra claparedii Grube, 1878 Aqueous Extract on Chang Liver and Human Primary Glioblastoma (U-87) Cell Lines

Universiti Malaysia Terengganu Journal of Undergraduate Research ◽

10.46754/umtjur.v1i3.79 ◽

2019 ◽

Vol 1 (3) ◽

pp. 56-67

Author(s):

Amirah Idris ◽

Izwandy Idris ◽

Wan Iryani Wan Ismail

Keyword(s):

Cell Growth ◽

Cancer Cells ◽

Cell Lines ◽

Aqueous Extract ◽

Normal Cell ◽

Cellular Growth ◽

Growth Effect ◽

Normal Cells ◽

Primary Glioblastoma ◽

Chang Liver

Due to the distinctive regenerative ability of Diopatra claparedii Grube, 1878, the local marine polychaete has the potential as a cellular growth agent. In this study, the growth effect was investigated in normal cells and cancer cells. Different concentrations (0-100mg/mL) of D. claparedii aqueous extract were tested on Chang Liver (normal cells), and Human Primary Glioblastoma (U-87) (cancer cells) cell lines for 24, 48 and 72 hours. Percentage of cell viability was evaluated by [2-(4, 5-dimethyl-2-thiazolyl)-3, 5-diphenyl-2H tetrazolium bromide] (MTT) assay. The findings suggested that the extract had a proliferative effect on normal cell growth when tested at lower doses (<60 mg/mL) but inhibited normal cells at concentrations >80 mg/mL in all incubation periods. Meanwhile, it showed the cytotoxic effect on cancer cells only after 48h when treated with all concentrations. As demonstrated, the extract could induce normal cell growth without causing abnormal or cancer cells progression at low concentrations after 48h and 72h.

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Melatonin Reprograms Glucose Metabolism in Cancer Cell Mitochondria

Series of Endocrinology, Diabetes and Metabolism ◽

10.54178/jsedmv1i3001 ◽

2019 ◽

Vol 1 (3) ◽

pp. 52-61

Author(s):

Russel J. Reiter ◽

Keyword(s):

Cancer Cells ◽

Cancer Cell ◽

Pyruvate Dehydrogenase Complex ◽

Cancer Growth ◽

Cell Phenotype ◽

Acetyl Coa ◽

History Of ◽

Cancer Phenotype ◽

High Concentrations ◽

The Warburg Effect

Melatonin has a long history of studies which confirm its ability to inhibit cancer growth. Melatonin is present in high concentrations in the mitochondria of normal cells but is likely absent from the mitochondria of cancer cells, at least when isolated from tumors harvested during the day. Herein, we hypothesize that melatonin’s absence from cancer cell mitochondria prevents these organelles from metabolizing pyruvate to acetyl coenzyme A (acetyl-CoA) due to suppression of the activity of the enzyme pyruvate dehydrogenase complex (PDC), the enzyme that catalyzes the conversion of pyruvate to acetyl-CoA. This causes cancer cells to metabolize glucose to lactate in the cytosol (the Warburg effect). Since cancer cell mitochondria can take up nighttime pineal-derived melatonin from the blood, the indoleamine predictably promotes the conversion of pyruvate to acetyl-CoA in the mitochondria during the night. Thus, while cancer cells exhibit a typical cancer phenotype during the day, at night cancer cells have a more normal cell phenotype. Via similar actions, melatonin probably overcomes the insensitivity of cancers to chemotherapies. Hopefully, the hypothetical processes proposed herein will soon be experimentally tested.

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The Versatile Effects of Dihydromyricetin in Health

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2017/1053617 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 18

Author(s):

Hongliang Li ◽

Qisheng Li ◽

Zhaowen Liu ◽

Kai Yang ◽

Zhixi Chen ◽

...

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Glucose Metabolism ◽

Adverse Effects ◽

Cancer Cells ◽

Ros Generation ◽

Normal Cells ◽

Potential Applications ◽

Anti Inflammatory ◽

Ampelopsis Grossedentata

Dihydromyricetin is a flavonoid isolated from Ampelopsis grossedentata, which is traditionally used in China. Dihydromyricetin exhibits health-benefiting activities with minimum adverse effects. Dihydromyricetin has been demonstrated to show antioxidative, anti-inflammatory, anticancer, antimicrobial, cell death-mediating, and lipid and glucose metabolism-regulatory activities. Dihydromyricetin may scavenge ROS to protect against oxidative stress or potentiate ROS generation to counteract cancer cells selectively without any effects on normal cells. However, the low bioavailability of dihydromyricetin limits its potential applications. Recent research has gained positive and promising data. This review will discuss the versatile effects and clinical prospective of dihydromyricetin.

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Combinatorial discovery of Mo-based polyoxometalate clusters for tumor photothermal therapy and normal cell protection

Biomaterials Science ◽

10.1039/d0bm01015d ◽

2020 ◽

Vol 8 (21) ◽

pp. 6017-6024

Author(s):

Wancheng Zhao ◽

Jingguo Wang ◽

Henan Wang ◽

Shuting Lu ◽

Yan Song ◽

...

Keyword(s):

Cancer Cells ◽

Photothermal Therapy ◽

Normal Cell ◽

Cell Protection ◽

Normal Cells

Molybdenum (Mo)-based polyoxometalate clusters can kill cancer cells selectively by PTT assay and protect the normal cells by scavenging ROS effectively.

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Significance of low-carbohydrate diets and fasting in patients with cancer

Roczniki Państwowego Zakładu Higieny ◽

10.32394/rpzh.2019.0083 ◽

2019 ◽

pp. 325-336

Keyword(s):

Growth Factors ◽

Glucose Metabolism ◽

Cancer Cells ◽

Standard Treatment ◽

The Other ◽

Normal Cells ◽

Tumor Mass ◽

Patients With Cancer ◽

Low Carbohydrate ◽

The Relationship

The differences between the metabolism and the physiology of cancer cells and the cells of the human body are assessed and used in most anticancer treatments. These differences encompass, among others, increased glucose metabolism in the changed cells. The aim of the paper was to discuss the results of studies concerning the relationship between lowcarbohydrate diets and fasting and the course of cancer. An inappropriately composed diet consisting of high amounts of simple sugars supplies cancer cells with nutrients, which may impair the effectiveness of cancer patients treatment. Lowcarbohydrate diets may, therefore, constitute an element of supplementary therapy in cancer treatment. The mechanism of low-carbohydrate diets in combination with standard treatment has not been completely explained, though. In initial studies it was proven that patients who were able to continue low-carbohydrate diets showed improvement in health and reduction of tumor mass or its slower growth. Moreover, it was observed that the inability of cancer cells to adapt in new environmental conditions that occur while fasting may have toxic effect on them. Introduction of fasting may sensitize cancer cells to chemotherapy, decrease concentration of growth factors and lead to repair of normal cells. On the other hand, fasting may also promote autophagy and, as can be concluded from the literature, its mechanism may have twofold activity: as a process impacting the survival or death of cancer cells.

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Inhibition of mitochondrial pyruvate dehydrogenase kinase: a proposed mechanism by which melatonin causes cancer cells to overcome cytosolic glycolysis, reduce tumor biomass and reverse insensitivity to chemotherapy

Melatonin Research ◽

10.32794/mr11250033 ◽

2019 ◽

Vol 2 (3) ◽

pp. 105-119 ◽

Cited By ~ 19

Author(s):

Russel J Reiter ◽

Ramaswamy Sharma ◽

Qiang Ma ◽

Sergio Rosales-Corral ◽

Dario Acuna-Castroviejo ◽

...

Keyword(s):

Breast Cancer ◽

Oxidative Phosphorylation ◽

Cancer Cells ◽

Pyruvate Dehydrogenase ◽

Warburg Effect ◽

Breast Cancer Cells ◽

Pyruvate Dehydrogenase Kinase ◽

Cell Phenotype ◽

Acetyl Coa ◽

The Warburg Effect

This review presents a hypothesis to explain the role of melatonin in regulating glucose metabolism in cancer cells. Many cancer cells use cytosolic glycolysis (the Warburg effect) to produce energy (ATP). Under these conditions, glucose is primarily converted to lactate which is released into the blood in large quantities. The Warburg effect gives cancer cells advantages in terms of enhanced macromolecule synthesis required for accelerated cellular proliferation, reduced cellular apoptosis which enhances tumor biomass and a greater likelihood of metastasis. Based on available data, high circulating melatonin levels at night serve as a signal for breast cancer cells to switch from cytosolic glycolysis to mitochondrial glucose oxidation and oxidative phosphorylation for ATP production. In this situation, melatonin promotes the synthesis of acetyl-CoA from pyruvate; we speculate that melatonin does this by inhibiting the mitochondrial enzyme pyruvate dehydrogenase kinase (PDK) which normally inhibits pyruvate dehydrogenase complex (PDC), the enzyme that controls the pyruvate to acetyl-CoA conversion. Acetyl-CoA has several important functions in the mitochondria; it feeds into the citric acid cycle which improves oxidative phosphorylation and, additionally, it is a necessary co-factor for the rate limiting enzyme, arylalkylamine N-acetyltransferase, in mitochondrial melatonin synthesis. When breast cancer cells are using cytosolic glycolysis (during the day) they are of the cancer phenotype; at night when they are using mitochondria to produce ATP via oxidative phosphorylation, they have a normal cell phenotype. If this day:night difference in tumor cell metabolism is common in other cancers, it indicates that these tumor cells are only cancerous part of the time. We also speculate that high nighttime melatonin levels also reverse the insensitivity of tumors to chemotherapy.

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Monosodium glutamate administration early in life alters pineal melatonin nocturnal profile in adulthood

Melatonin Research ◽

10.32794/mr11250084 ◽

2021 ◽

Vol 4 (1) ◽

pp. 99-114

Author(s):

Janaína B Garcia ◽

Fernanda G Do Amaral ◽

Daniela C Buonfiglio ◽

Rafaela FA Vendrame ◽

Patrícia L Alves ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Pineal Gland ◽

Serum Insulin ◽

Monosodium Glutamate ◽

Female Rats ◽

Pineal Melatonin ◽

Melatonin Synthesis ◽

Male And Female Rats ◽

Melatonin Production

The pineal gland synthesizes melatonin exclusively at night, which gives melatonin the characteristic of a temporal synchronizer of the physiological systems. Melatonin is a regulator of insulin activities centrally and also peripherally and its synthesis is reduced in diabetes. Since monosodium glutamate (MSG) is often used to induce the type 2 diabetic and metabolic syndrome in animal models, the purpose of this work is to evaluate the potential effects of MSG given to neonates on the pineal melatonin synthesis in different aged male and female rats. Wistar rats were subcutaneously injected with MSG (4mg/g/day) or saline solution (0.9%) from the second to eighth post-natal day. The circadian profiles both melatonin levels and AANAT activity were monitored at different ages. Body weight, naso-anal length, adipose tissues weight, GTT, ITT and serum insulin levels were also evaluated. Typical obesity with the neonatal MSG treatment was observed, indicated by a great increase in adipose depots without a concurrent increase in body weight. MSG treatment did not cause hyperglycemia or glucose intolerance, but induced insulin resistance. An increase of melatonin synthesis at ZT 15 with phase advance was observed in in some animals. The AANAT activity was positively parallel to the melatonin circadian profile. It seems that MSG causes hypothalamic obesity which may increase AANAT activity and melatonin production in pineal gland. These effects were not temporally correlated with insulin resistance and hyperinsulinemia indicating the hypothalamic lesions, particularly in arcuate nucleus induced by MSG in early age, as the principal cause of the increase in melatonin production.

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