Activity of Melatonin Against Gastric Cancer Growth in a Chick Embryo Tumor Xenograft Model

Wang, Rixiong; Liu, Hui; Jun, Sangook; Wu, Qing

doi:10.2147/cmar.s329728

Cited by 5 publications

(2 citation statements)

References 35 publications

(23 reference statements)

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“…Here, we found that the levels of endocan were higher in control tumoroids in comparison with the melatonin-treated groups. One possible mechanism would be that the inner dark necrotic area contains higher levels of pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin-1, leading to the induction of endocan and VEGF-A [ 37 , 38 ]. It has been indicated that the exposure of hypoxic cells to melatonin can reduce the production of angiogenesis factors [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Melatonin blunted the angiogenic activity in 3D colon cancer tumoroids by the reduction of endocan

Narmi,

Shoja,

Haiaty

et al. 2023

Cancer Cell Int

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Background Complexity and heterogeneity of the tumor niche are closely associated with the failure of therapeutic protocols. Unfortunately, most data have been obtained from conventional 2D culture systems which are not completely comparable to in vivo microenvironments. Reconstructed 3D cultures composed of multiple cells are valid cell-based tumor models to recapitulate in vivo-like interaction between the cancer cells and stromal cells and the oncostatic properties of therapeutics. Here, we aimed to assess the tumoricidal properties of melatonin on close-to-real colon cancer tumoroids in in vitro conditions. Methods Using the hanging drop method, colon cancer tumoroids composed of three cell lines, including adenocarcinoma HT-29 cells, fibroblasts (HFFF2), and endothelial cells (HUVECs) at a ratio of 2: 1: 1, respectively were developed using 2.5% methylcellulose. Tumoroids were exposed to different concentrations of melatonin, from 0.005 to 0.8 mM and 4 to 10 mM, for 48 h. The survival rate was measured by MTT and LDH leakage assays. Protein levels of endocan and VEGF were assessed using western blotting. Using histological examination (H & E) staining, the integrity of cells within the tumoroid parenchyma was monitored. Results Despite the reduction of viability rate in lower doses, the structure of tumoroids remained unchanged. In contrast, treatment of tumoroids with higher doses of melatonin, 4 and 10 mM, led to disaggregation of cells and reduction of tumoroid diameter compared to the non-treated control tumoroids (p < 0.05). By increasing melatonin concentration from 4 to 10 mM, the number of necrotic cells increased. Data showed the significant suppression of endocan in melatonin-treated tumoroids related to the non-treated controls (p < 0.05). According to our data, melatonin in higher doses did not alter protein levels of VEGF (p > 0.05). Conclusions Melatonin can exert its tumoricidal properties on colon cancer tumoroids via the reduction of tumor cell viability and inhibition of the specific pro-angiogenesis factor.

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Section: Discussionmentioning

confidence: 99%

Melatonin blunted the angiogenic activity in 3D colon cancer tumoroids by the reduction of endocan

Narmi,

Shoja,

Haiaty

et al. 2023

Cancer Cell Int

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“…Melatonin suppresses tumor promotion by upregulating p53 [ 31 ]. Moreover, melatonin was reported to inhibit cancer growth by downregulating VEGF [ 32 ] and AKT [ 33 ] in vivo.…”

Section: Anticancer Effect Of Melatoninmentioning

confidence: 99%

Use of Melatonin in Cancer Treatment: Where Are We?

Wang

Choi

2022

IJMS

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Cancer represents a large group of diseases accounting for nearly 10 million deaths each year. Various treatment strategies, including surgical resection combined with chemotherapy, radiotherapy, and immunotherapy, have been applied for cancer treatment. However, the outcomes remain largely unsatisfying. Melatonin, as an endogenous hormone, is associated with the circadian rhythm moderation. Many physiological functions of melatonin besides sleep–wake cycle control have been identified, such as antioxidant, immunomodulation, and anti-inflammation. In recent years, an increasing number of studies have described the anticancer effects of melatonin. This has drawn our attention to the potential usage of melatonin for cancer treatment in the clinical setting, although huge obstacles still exist before its wide clinical administration is accepted. The exact mechanisms behind its anticancer effects remain unclear, and the specific characters impede its in vivo investigation. In this review, we will summarize the latest advances in melatonin studies, including its chemical properties, the possible mechanisms for its anticancer effects, and the ongoing clinical trails. Importantly, challenges for the clinical application of melatonin will be discussed, accompanied with our perspectives on its future development. Finally, obstacles and perspectives of using melatonin for cancer treatment will be proposed. The present article will provide a comprehensive foundation for applying melatonin as a preventive and therapeutic agent for cancer treatment.

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