Melatonin: From Basic Research to Cancer Treatment Clinics

2002 ◽  
Vol 20 (10) ◽  
pp. 2575-2601 ◽  
Author(s):  
Vijayalaxmi ◽  
Charles R. Thomas ◽  
Russel J. Reiter ◽  
Terence S. Herman
Keyword(s):  
Cancer Treatment ◽  
Basic Research ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Secretory Product ◽  
Drug Induced ◽  
Radiation Induced ◽  
Laboratory Investigations

ABSTRACT: Melatonin, the chief secretory product of the pineal gland, is a direct free radical scavenger, an indirect antioxidant, as well as an important immunomodulatory agent. In both in vitro and in vivo investigations, melatonin protected healthy cells from radiation-induced and chemotherapeutic drug–induced toxicity. Furthermore, several clinical studies have demonstrated the potential of melatonin, either alone or in combination with traditional therapy, to yield a favorable efficacy to toxicity ratio in the treatment of human cancers. This study reviews the literature from laboratory investigations that document the antioxidant and oncostatic actions of melatonin and summarizes the evidence regarding the potential use of melatonin in cancer treatment. This study also provides rationale for the design of larger translational research–based clinical trials.

scholarly journals Day and Night GSH and MDA Levels in Healthy Adults and Effects of Different Doses of Melatonin on These Parameters

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
Shilpa Chakravarty ◽  
Syed Ibrahim Rizvi
Keyword(s):  
Oxidative Stress ◽  
Membrane Lipid ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Secretory Product ◽  
Therapeutic Implications ◽  
Antioxidative Function ◽  
Reliable Marker

The pineal secretory product melatonin (chemically, N-acetyl-5-methoxytryptamine) acts as an effective antioxidant and free-radical scavenger and plays an important role in several physiological functions such as sleep induction, immunomodulation, cardiovascular protection, thermoregulation, neuroprotection, tumor-suppression and oncostasis. Membrane lipid-peroxidation in terms of malondialdehyde (MDA) and intracellular glutathione (GSH) is considered to be a reliable marker of oxidative stress. The present work was undertaken to study the modulating effect of melatonin on MDA and GSH in human erythrocytes during day and night. Our observation shows the modulation of these two biomarkers by melatonin, and this may have important therapeutic implications.In vitrodose-dependent effect of melatonin also showed variation during day and night. We explain our observations on the basis of melatonin's antioxidative function and its effect on the fluidity of plasma membrane of red blood cells. Rhythmic modulation of MDA and GSH contents emphasized the role of melatonin as an antioxidant and its function against oxidative stress.

A Novel Free Radical Scavenger, Edarabone, Protects Against Cisplatin-Induced Acute Renal Damage in Vitro and in Vivo

2003 ◽  
Vol 305 (3) ◽  
pp. 1183-1190 ◽  
Author(s):  
Minoru Satoh ◽  
Naoki Kashihara ◽  
Sohachi Fujimoto ◽  
Hideyuki Horike ◽  
Takehiko Tokura ◽  
...  
Keyword(s):  
Free Radical ◽  
Renal Damage ◽  
Free Radical Scavenger ◽  
Radical Scavenger

scholarly journals Reviews on Mechanisms ofIn VitroAntioxidant Activity of Polysaccharides

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Junqiao Wang ◽  
Shuzhen Hu ◽  
Shaoping Nie ◽  
Qiang Yu ◽  
Mingyong Xie
Keyword(s):  
Antioxidant Activities ◽  
Cell Structure ◽  
Free Radical Scavenger ◽  
Antioxidant Systems ◽  
Radical Scavenger ◽  
Significant Damage ◽  
Nonenzymatic Antioxidants ◽  
Underlying Mechanisms

It is widely acknowledged that the excessive reactive oxygen species (ROS) or reactive nitrogen species (RNS) induced oxidative stress will cause significant damage to cell structure and biomolecular function, directly or indirectly leading to a number of diseases. The overproduction of ROS/RNS will be balanced by nonenzymatic antioxidants and antioxidant enzymes. Polysaccharide or glycoconjugates derived from natural products are of considerable interest from the viewpoint of potentin vivoandin vitroantioxidant activities recently. Particularly, with regard to thein vitroantioxidant systems, polysaccharides are considered as effective free radical scavenger, reducing agent, and ferrous chelator in most of the reports. However, the underlying mechanisms of these antioxidant actions have not been illustrated systematically and sometimes controversial results appeared among various literatures. To address this issue, we summarized the latest discoveries and advancements in the study of antioxidative polysaccharides and gave a detailed description of the possible mechanisms.

scholarly journals Skin fibroblasts from spermine synthase-deficient hemizygous gyro male (Gy/Y) mice overproduce spermidine and exhibit increased resistance to oxidative stress but decreased resistance to UV irradiation

2000 ◽  
Vol 352 (2) ◽  
pp. 381-387 ◽  
Author(s):  
Jonas NILSSON ◽  
Amel GRITLI-LINDE ◽  
Olle HEBY
Keyword(s):  
Oxidative Stress ◽  
Free Radical ◽  
Primary Cultures ◽  
Free Radical Scavenger ◽  
Skin Fibroblasts ◽  
Radical Scavenger ◽  
Spermine Synthase ◽  
Y Cells

Hemizygous gyro male (Gy/Y) mice are a model for X-linked hypophosphataemic rickets. As in humans, the disease is caused by deletions in the Phex gene, a phosphate-regulating gene having homologies with endopeptidases on the X chromosome. Some phenotypic abnormalities in Gy/Y mice have recently been attributed to the fact that the Gy deletion also includes the neighbouring spermine synthase gene, resulting in spermine deficiency. Spermine and its precursors spermidine and putrescine are essential for cell growth and differentiation. As a novel method for studying the function of spermine, we established primary cultures of skin fibroblasts from hemizygous Gy/Y mice. The Gy/Y cells contained no detectable spermine. In view of the fact that spermine is a free-radical scavenger in vitro, we were surprised to find that Gy/Y cells were more resistant to oxidative stress than their normal (X/Y) counterparts. However, our finding that spermidine accumulates markedly in the spermine-deficient Gy/Y cells can probably explain this increased resistance. It is the first indication that spermidine can serve as a free-radical scavenger in vivo and not only in vitro. When subjecting the Gy/Y cells to UV-C irradiation we made another interesting finding: the mutant cells were more sensitive than the normal X/Y cells. This finding indicates that spermine, probably because of its high-affinity binding to DNA, is important in protection against chromatin damage.

Recent Advances in Liposomal Drug Delivery System of Quercetin for Cancer Targeting: A Mechanistic Approach

2020 ◽  
Vol 17 (10) ◽  
pp. 845-860 ◽  
Author(s):  
Sabya S. Das ◽  
Afzal Hussain ◽  
Priya R. Prasad Verma ◽  
Syed S. Imam ◽  
Mohammad A. Altamimi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Oral Drug Delivery ◽  
Aqueous Solubility ◽  
Free Radical Scavenger ◽  
Oral Drug ◽  
Radical Scavenger ◽  
Solid Cancer ◽  
Liposomal Drug

Quercetin (QT, 3,3′,4′,5,7-pentahydroxyflavone), is a natural flavonoid with nutritional value and acts as a potential free-radical scavenger (antioxidant). QT has also been explored for its anti-cancer as well as anti-proliferative activities against numerous cancerous cells. Moreover, QT exhibits significant pro-apoptotic activity against tumor cells and is well established to control the growth of different carcinoma cells at various phases of the cell cycle. Hence, it can reduce the burden of human solid cancer and metastasis. Both these activities have been established in a diverse class of human cell lines in-vitro as well as in animal models (in-vivo). Apart from the promising therapeutic activities of QT molecule, their applications have been limited due to some major concerns, including low oral bioavailability and poor aqueous solubility. Also, rapid gastrointestinal digestion of QT seems to be a key barrier for its clinical translations for oral drug delivery in conventional dosage form. Henceforth, to overcome these drawbacks, QT is loaded with liposomal systems, which exhibit promising outcomes in the upregulation of QT by the epithelial system and also improved its targeting at the site of action. Furthermore, Liposomes based Drug Delivery Systems (LDDS) have showed significant therapeutic activity with conjugated drug moiety and exhibit safety, biocompatibility, biodegradability, and mitigated toxicity despite having certain limitations associated with physiological and biological barriers. Herein, in this review, we have focused on the mechanism related with the chemotherapeutic activity of QT and also discussed the promising activity of QT-loaded LDDS as a potent chemotherapeutic agent for cancer therapy.

Necroptosis Triggered by ROS Accumulation and Ca2+ Overload, Partly Explains the Inflammatory Responses and Anti-Cancer Effects Associated With 1Hz, 100 mT ELF-MF in vivo

2020 ◽  
Author(s):  
Mojdeh Barati ◽  
Mohammad Amin Javidi ◽  
Behrad Darvishi ◽  
Seyed Peyman Shariatpanahi ◽  
Zahra S. Mesbah Moosavi ◽  
...  
Keyword(s):  
Cell Death ◽  
Inflammatory Responses ◽  
Low Frequency ◽  
Tumor Infiltrating Lymphocytes ◽  
Free Radical Scavenger ◽  
Radical Scavenger ◽  
Ki 67 ◽  
Infiltrating Lymphocytes

Abstract Background: Focus on application of non-ionizing, extremely low frequency magnetic fields (ELF-EMF) as an alternative approach for treating cancer is rapidly rising nowadays. Nevertheless, little is known about the underlying anti-tumoral mechanism of action of them. Methods: In the present study, for the first time, we reported that along with apoptosis, 2 h/day exposure to 100 Hz, 1 mT ELF-EMF for a 5-day period, can induce necroptosis, a specific type of programed necrotic cell death, by promoting RIPK1/RIPK3/MLKL pathway which may also be responsible for observed pro-inflammatory responses in vivo, evident from an increase in plasma levels of pro-inflammatory cytokines including TNF-α, IL-1β, IL-2, IL-6, IL-17A and IFN-γ. Alongside, 30-day exposure to this system could also significantly suppress tumor growth and expression of markers of tumor cell proliferation, angiogenesis, and metastasis, namely Ki-67, CD31, VEGFR2 and MMP-9. Results: The number of tumor infiltrating lymphocytes (TILs), especially CD8+ Th cells were significantly increased following exposure to ELF-EMF. Interestingly, pretreating cancer cells with N-acetyl cysteine, a free-radical scavenger, or verapamil, an L-type calcium channel blocker in vitro, could diminish observed necroptotic and apoptotic responses while pretreating with calcium chloride, could aggravate responses.Conclusions: Overall, results of present study demonstrated that along with apoptosis, necroptosis is also a prominent form of cell death induced by exposure to ELF-EMF which is also dependent on elevated intracellular levels of ROS and calcium.

Melatonin Loading Chitosan-Tripolyphosphate Nanoparticles: Application in Attenuating Etoposide-Induced Genotoxicity in HepG2 Cells

Pharmacology ◽  
2018 ◽  
Vol 102 (1-2) ◽  
pp. 74-80 ◽  
Author(s):  
Mohammad Shokrzadeh ◽  
Nasrin Ghassemi-Barghi
Keyword(s):  
Hepg2 Cells ◽  
Topoisomerase Ii ◽  
Reactive Oxygen Species Generation ◽  
Chemotherapeutic Agents ◽  
Free Radical Scavenger ◽  
Control Group ◽  
Radical Scavenger ◽  
Etoposide Treatment

Etoposide is one of the most effective chemotherapeutic agents used in the treatment of various types of cancers. However, as a Topoisomerase II inhibitor, during clinical use, several side effects may occur. In addition, in several in vivo and in vitro studies, etoposide has been shown to have a range of genotoxic effects including single and double strand breaks. Melatonin is an anti-aging and antioxidant hormone synthesized from the pineal gland. The genoprotective, antioxidant, and free radical scavenger properties of melatonin have been well explained in various studies. The aim of this study was to explore whether melatonin nanoparticles protects against etoposide-induced genotoxicity in the HepG2 cell line. HepG2 cells (25 × 104 cells/well) were cultured in 24-well plates: a control group and 3 melatonin and its nanoparticles + etoposide groups (pre- and cotreatment conditions). Our results show that etoposide induced a noticeable genotoxic effect in HepG2 cells. Melatonin reduced the effects of etoposide significantly in both types of experiment conditions, through the reduction of the level of DNA damage measured via comet assay. Furthermore, melatonin decreased the intracellular reactive oxygen species generation. It also increased the intracellular glutathione levels in HepG2 cells. Nano melatonin is more effective than regular melatonin. The most protective effect was observed with melatonin when it was administrated 24 h before etoposide treatment.

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