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Background and purpose: Melatonin is a neurohormone with important physiologic and pharmacologic role in human body especially in circadian rhythm .In recent years, some progress has been achieved to show its role in regulating in prevention of cancer especially breast and colon cancer. According to this background and as there was not any precise cellular research about the role of melatonin in gastric cancer in which this study this study has been aimed. Materials and methods: In this study, we used MTT assay procedure. Also, we have provided AGS and MKN-45 cell line from national cell bank, Institute Pasteur of Iran. The cells were cultured in RPMI medium in 5% CO2, 370C in 96 wells culture plate and then were incubated with melatonin and cisplatin (as positive control) for 48 hr. in 5 different concentrations. The proliferation index as cell viability was achieved and compared with controls groups with ELISA concerning Formazan crystal color absorbance between 450-690 nm. Results: Our results showed that melatonin in 12.5-200 µM has significant anti-proliferative effects in AGS cells and in 50-200 µM in MKN-45 compared with control and these results were in parallel with the effects of cisplatin. Conclusion: According to our data, we have shown that melatonin in a dose -dependent manner has antiproliferative effect in gastric adenocarcinoma cells and this effect in AGS cells was more potent than MKN-45 but more studies are needed to find the kind of receptors and the interacellular signaling pathways.

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Background and purpose: According to recent studies melatonin has been known as a potent anti-oxidant with anti-oncostatic and cytoprotective properties. The gastrointestinal tract is the major source of melatonin in periphery. Therefore, many scientists suppose a protective role for melatonin in gastrointestinal tract. Also, there is a high rate of gastric adenocarcinoma in Mazandaran province of Iran, so this study investigated the expression of melatonin receptor in gastrointestinal patients with focusing on MT2 as an important melatonin receptor which its role in many cancers has been shown peviously. Materials and methods: Gastric adenocarcinoma patients from Mazandaran province of Iran were selected for this study and normal individuals as control. After extracting RNA from 30 gastric cancer tissues and 30 normal tissues and preparing cDNA, the expression of melatonin receptor (type 2) has been assayed with Real-time PCR. Results: Our experiment has been shown for the first time in Mazandarn province, high expression of melatonin receptor type 2 in gastric cancer tissues compared to control.Also it was revealed that this expression in marginal of cancer patients was more than cancer tissues and negative control. Conclusion: In this study for the first time we found the expression of melatonin receptor in gastric adenocarcinoma tissues which was in consistent with other studies as breast and colon cancer and a high expression in marginal tissues indicates a refractory mechanism and defending role of melatonin in GI system .Also high experession of this receptor in gastric cancer people of Mazandarn province may help to know better the etiology of high incidence of this kind of cancer in this area.

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Background and purpose: Oxidative stress inhibits sperm motility and changes in shape and be individuals leads to sterility. Cadmium, increased free radical production in cells and cell tissue damage. The best way to deal with it, increasing antioxidants secret among the antioxidants melatonin as an antioxidant was studied. Materials and methods: 64 male Wistar rats over 6-8 weeks were divided into 8 groups of 8, (two control groups and six experimental groups). The first group was injected intra peritoneal with a single daily dose of 10 mg / kg melatonin injection for 30 days, the second group injected intra peritoneal with a single daily dose of 15 mg / kg melatonin injection for 30 days, Group III intra peritoneal single daily dose of 20 mg / kg melatonin injection for 30 days. Group IV as a positive control group was injected intra peritoneal with a single daily dose of 2 mg / kg for 30 days Cadmium chloride injection, the fifth group intra peritoneal with a daily single dose of 2 mg / kg - Cadmium chloride with 10 mg daily of g / kg melatonin injection for 30 days , six daily intra peritoneal with a single dose of 2 mg / kg daily- Cadmium chloride with a single 15 mg / kg melatonin injection for 30 days , Group VII intra peritoneal dose single daily dose of 2 mg / kg daily Cadmium chloride with a single 20 mg / kg melatonin were injected for 30 days .Group of Eight negative control group received intra peritoneal injection of physiological solution. Testicular volume and weight measurements and cell counts based on morphology and testis were examined. Results: Results showed a significant reduction of the layer thickness and the number of germ cells Cadmium chloride group (P <0/05) and this was significantly different between the groups receiving melatonin to increase the layer thickness and the number of germ cells (P <0/05) compared to the control group and the group receiving both drugs simultaneously, particularly the significant differences in the groups receiving 20 mg of melatonin was compared to the group receiving cadmium alone (P <0/05). Conclusion: The present study shows the effects of cadmium chloride damage sperm activity and morphology of testis and melatonin are the property antioxidant, causing the low the effects of cadmium chloride on testicular improve spermatogenesis, increasing the number of cells and germinal layer thickness and ultimately will improve fertility.

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Background and purpose: Recently studies have shown that main compound (Cyclotides) of Viola odorata has an inhibitory effect against proliferation of cancer cells. Also, melatonin reduces size and growth of tumor cells. The main purpose of this study was to compare the inhibitory effect of Viola odorata and melatonin on MDA-MB-468 cells proliferation. Materials and methods: In this exprimental study, triple negative human breast cancer cells (MDA-MB-468) were cultured in 96-well plates and incubated with different concentrations of Viola odorata hydroalcoholic extract and melatonin for 24h. Cell viability was measured using MTT assay. In the in vivo study Balb/c mice (6 group, n=6) received subcutaneous injection of 100 µl of cell suspension (4T1 cells) in the left hind flank. The animals were treated with different concentrations of Viola odorata extract (50, 150, 250, and mg/kg) and melatonin (40 mg/kg) for three weeks. Tumor volume changes were measured weekly and weight changes were measured at day 21. Results: The in vitro study showed that different concentrations (30, 40, 60, 80,100,150, and 200 µg/ml) of Viola odorata significantly decreased cell survival in cancer cells (P<0.05). Also, melatonin at concentration of 1mM significantly decreased cell viability (P<0.05). The in vivo study found that melatonin (40 mg/kg) and Viola odorata at 250 mg/ml concentration inhibited increasing of tumor volume after 21 days compared with control group. Conclusion: Treatment with melatonin and Viola odorata extract was found effective in reducing cell survival and tumor volume.

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Background and purpose: Viola odorata is a medical plant used in the treatment of hepatic disorders and relieving cancer pain. Melatonin (Mel) can act as an antioxidant and prevent cells against oxidative stress. This compound has a direct inhibitory effect on cancer cell proliferation. In the present study, we performed an in-vivo study to evaluate the effects of Viola odorata hydro-alcoholic extract (VOE) and MEL on tumor growth and NF-kB, TNFR1, and VCAM-1 expression rate in 4T1 breast cancer model.

Materials and methods: In this experimental study, 4T1 cells, which were cultured in-vitro, were harvested and put in a serum-free suspension medium. The animals (five groups, n=5) received subcutaneous injections of 0.1 ml of cell suspension (0.8 million cells) in the right mammary gland or hind flank. The implanted BALB/c mice with 4T1 cells were treated with different concentrations of VOE (50, 150, and 250 mg/kg) and Mel (40 mg/kg) for 21 days. The control group received distilled water. The mice were sacrificed on day 22. NF-kB, TNFR1, and VCAM-1 expression rate was measured by Western Blotting technique. To analyze the data, ANOVA test was run in SPSS, version 16.

Results: The size of tumors in Mel (P=0.000) and VOE250 (P=0.0001) treated mice was smaller compared to that of the control group. Our results indicated that Mel (P=0.022) and VOE250 (P=0.02) increased TNFR1 expression. On the other hand, Mel (P=0.034) and VOE150 (P=0.04) decreased VCAM-1 expression in the 4T1 breast cancer model. Unlike the Mel group, NF-kB expression reduced in the group receiving VOE250 compared to that of the control group (P=0.012).

Conclusion: It seems that VOE and Mel can reduce the rate of tumor growth in 4T1 breast cancer model by decreasing the expression of VCAM-1 and NF-kB and enhancing the expression of TNFR1.

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Background and purpose: The aim of this study was to bioinformatically and experimentally evaluate the effect of melatonin on the expression levels of UBE2W and SSX2IP genes in melatonin treated Human Hepatocellular carcinoma G2 (HepG2) cancer cell line. UBE2W encodes a protein that promotes ubiquitination of Fanconi anemia complementation group proteins and may be important in the repair of DNA damage. SSX2IP belongs to an adhesion system, involved in cell movement and acts as a centrosome maturation factor.
Materials and methods: At first, as a bioinformatics tool, MATLAB 2018a software was employed to evaluate the UBE2W and SSX2IP genes expression levels using microarray data. Then, after designing and preparing the primers, MTT and Real-time PCR were carried out in three replicates.
Results: MTT assay showed that the viability of cancer cell significantly decreased in melatonin treated group (P≤0.01). The IC₅₀ value was estimated to be 2080 µM for 48 hours, but no significant changes were seen in the survival of human normal cells (HUVEC-C) (P≥0.05). Real-time PCR proved that the expression levels of both genes increased (P≥0.05 in 24h and P≤ 0.05 in 48h) in melatonin treated cells compared to un-treated group, which was in accordance with bioinformatics analysis.
Conclusion: Our study showed that UBE2W and SSX2IP genes could be used as therapeutic target genes for Hepatocellular carcinoma. However, complementary studies are needed to prove current findings.

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Cancer is one of the most challenging diseases, affecting millions of individuals worldwide. This disease is caused by the abnormal and uncontrolled growth of cells, which leads to damage to various tissues and organs of the body. The formation of vascular-like structures (vascular mimicry) is one of the most important reasons for cancer metastasis and drug resistance. These structures are formed by tumor cells without the involvement of endothelial cells. Melatonin, a natural hormone in the human body, can exert its antitumor effects through antioxidant, antiproliferative effects, induction of apoptosis, and inhibition of invasion and metastasis of cancer cells. The anticancer effects of apatinib have been approved as an antiangiogenic drug and VEGF receptor inhibitor. Apatinib is first used for advanced or metastatic cancers, such as gastric cancer, that have not responded to standard treatments. In addition, induction of apoptosis, inhibition of metastasis, and invasion have also been confirmed by treatment with apatinib in cancer. Considering the antitumor effects of melatonin and apatinib, it seems that the drug apatinib and the hormone melatonin are effective in inhibiting the formation of vascular mimicry and overcoming the therapeutic limitations caused by these structures. This review study examined the effects of melatonin and apatinib on the formation of vascular mimicry structures in various cancers. It is suggested that these two compounds enter the animal and then human study phases, and if the results are positive, they could be used as a treatment for patients with metastatic cancer.