A review on melatonin action as therapeutic agent in cancer

Nair, Soumya; Suresh, Sandra; Kaniyassery, Arya; Jaya, P.; Abraham, Jayanthi

doi:10.1007/s11515-018-1503-5

Cited by 3 publications

(2 citation statements)

References 75 publications

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“…Recent studies have shown that melatonin is not only secreted rhythmically by the pineal gland, but also can be synthesized by peripheral tissue cells, regulating the redox balance and microenvironmental immunity of target cells by paracrine or autocrine patern [15,16]. Numbers of relevant melatonin-dependent effects are triggered by targeting mitochondrial functions, including modulating the mitochondrial respiratory chain, antagonizing the highly glycolytic bioenergetic pathway, regulating Ca 2+ release and mitochondrial apoptotic effectors [17].…”

Section: Introductionmentioning

confidence: 99%

Neu-p11 induces NLRP3 inflammasome-induced pyroptosis via provoking NOX4-mediated mitochondrial oxidative injury in chordoma cells

Zhang

2020

Preprint

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Chordoma is a rarely malignant bone tumor with highly resistance to radiotherapy and chemotherapy. Melatonin has been shown to inhibit tumor cell invasion, metastasis and induce apoptosis in several types of cancer. Activation of melatonin receptor inhibit cancer stemness of chordoma, which suggesting that melatonin receptor agonists have potential therapeutic value for the clinical treatment of chordoma. The present study aimed to investigate the anticancer action and molecular mechanism of Piromelatine (Neu-P11) in chordoma cells, a high-efficacy agonist of melatonin receptor-1/melatonin receptor-2 (MT1/MT2). We used Neu-p11 (1, 10, 100, 1000 μM) or vehicle to treat chordoma cell lines U-CH1 and MUG-Chor for 36 hours. CCK-8 assay and LDH activity assay showed that Neu-p11 had dose-dependent cytotoxic effect on chordoma cells. Neu-p11 induced NLRP3 and Cleaved-Caspase-1 expression, while Caspase-1 specific inhibitor Z-YVAD-FMK and NLRP3 specific inhibitor MCC950 independently blocked the cytotoxic effect of Neu-p11 on chordoma cells, indicating that Neu-p11 induced a NLRP3-dependent cell pyroptosis. Neu-p11 promoted NADPH oxidase 4 (NOX4) translocation to mitochondria, resulting in a significant increase in mitochondria-derived ROS and decreased expressions of mitochondrial antioxidant proteins (MnSOD, Sirt3) and mitochondrial DNA replication factor (Tfam), which could be attenuated by NOX4 specific inhibitor GKT137831. Further investigation revealed that Neu-p11 resulted in decreased copy number of mtDNA and increased mtDNA releasing in cytoplasm. Decreased oxygen consumption, reduced membrane potential and ultrastructural damage of mitochondrial were detected in Neu-p11 treated chordoma cells, which could be attenuated by GKT137831. GKT137831 inhibited mitochondria-translocation of NLRP3 and attenuated activation of NLRP3 inflammasome caused by Neu-p11 treatment. Collectively, we demonstrated that Neu-p11 induces mitochondrial translocation of NOX4 leads to oxidative damage of mitochondria, mediating chordoma cells NLRP3-dependent pyroptosis. Neu-p11 may be a a new strategy for chordoma treatment. Graphic abstractAbbreviations Neu-p11, Piromelatine; NOX4, NADPH oxidase 4; NLRP3, NLR Family Pyrin Domain Containing 3; MnSOD, Manganese superoxide dismutase; Sirt3, NADdependent deacetylase sirtuin-3; Tfam, mitochondrial transcription factor A; mtROS, mitochondria-derived reactive oxygen species; mitochondrial membrane potential (MMP, ΔΨm); mtDNA, mitochondrial DNA.

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Section: Introductionmentioning

confidence: 99%

Neu-p11 induces NLRP3 inflammasome-induced pyroptosis via provoking NOX4-mediated mitochondrial oxidative injury in chordoma cells

Zhang

2020

Preprint

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“…Increase in substances such as proline can be one of the major molecular responses to drought stress [6]. Drought stress-induced free radicals cause lipid peroxidation and membrane deterioration in plants [7].…”

Section: Introductionmentioning

confidence: 99%

Amelioration of Drought Tolerance in Maize Using Rice Husk Biochar

Mannan¹,

Shashi²

2020

Maize - Production and Use

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This chapter discussed on mitigating effects of rice husk biochar to the drought effect on maize ("BARI Hybrid Bhutta 9"). Four doses of rice husk biochar at 0, 5, 10, and 20 t/ha were applied in soil before sowing of seed. Drought treatments were maintained at 60% of field capacity and 40% of field capacity by watering every alternate day, and 80% of field capacity (control) was also maintained as wellwatered treatment. Plant growth and physiological parameters were studied at 6th leaf, 10th leaf, 14th leaf, tasseling stage, cob initiation stage, and maturity stage, and yield contributing parameters were studied after harvest. Soil physical and chemical properties were studied before sowing and after harvest of crop. Drought stress reduced plant morphological growth and affected physiology and yield of maize. Mitigation of drought stress in maize was well associated with the reduction of proline content, maintenance of water-related traits, exudation rate and enhanced chlorophyll content and SPAD value, as well as dry matter production. Rice husk biochar improved the growth and yield performance of maize under drought condition. Biochar application at 20 t/ha was the best treatment to improving drought tolerance in maize.

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