In vitro effects of melatonin on cell proliferation in a colon adenocarcinoma line

Farriol, M.; Venereo, Y.; Orta, Xavi; Castellanos, J.M.; Segovia-Silvestre, Toni

doi:10.1002/(sici)1099-1263(200001/02)20:1<21::aid-jat623>3.0.co;2-m

Cited by 79 publications

(73 citation statements)

References 18 publications

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“…However, others were not able to confirm these preliminary results [86,87], even when an inhibitory effect on tumor growth was observed at high melatonin concentrations. No effect of melatonin on apoptosis was documented by Lewinski et al [88] or by Garcìa-Navarro and co-workers [89] in HT-29 colon cancer cells.…”

Section: Melatonin In Gastrointestinal and Colon Cancersmentioning

confidence: 99%

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review

Bizzarri

Proietti

Cucina

et al. 2013

Expert Opinion on Therapeutic Targets

176

145

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Melatonin involvement in apoptotic processes is a new and relevant field of investigation. Even in tumor models unresponsive to melatonin alone, this hormone can significantly amplify the cytostatic and the cytotoxic effects triggered by other compounds or conventional drugs. We are far from having a satisfactory understanding about how and when melatonin exerts its beneficial effects. Melatonin in the nanomolar range activates the intrinsic and/or the extrinsic apoptotic pathway in cancer cells, namely through an increase in the p53/MDM2p ratio and downregulation of Sirt1. This finding is of great relevance since there is intense research ongoing to identify nontoxic feasible inhibitors of MDM2 and Sirt1. Melatonin should be evaluated for the management of those cancers where both of these are overexpressed and functionally strategic.

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Section: Melatonin In Gastrointestinal and Colon Cancersmentioning

confidence: 99%

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review

Bizzarri

Proietti

Cucina

et al. 2013

Expert Opinion on Therapeutic Targets

176

145

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“…104 The effect of melatonin on inhibition of colon carcinoma cell growth was studied in CT-26 cells, a murine colon carcinoma-derived cell line. 105 Although melatonin had no effect on cell growth at low doses, a statistically significant and progressive suppression of DNA synthesis was found as melatonin doses increased (the percentage of inhibition being 1 mM, 22%; 2 mM, 25%; 3 mM, 47%). 105 Inasmuch as no receptors were involved in the cell line selected, it was concluded that melatonin exerted its anti-proliferative action through a nonhormonedependent mechanism.…”

Section: Melatonin In Colorectal Carcinomamentioning

confidence: 99%

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

et al. 2008

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189predisposing factors for the development of cancer in humans.2,3 A recent study involving 44 000 pairs of Scandinavian twins suggested that environmental factors are paramount contributors in cancer development. 4 The human body is well equipped with both immune and nonimmune anticarcinogenic mechanisms for fighting cancer. Natural killer (NK) lymphocytes play an important role in inhibiting tumor growth and metastases. 5 Many studies implicate oxidative stress in precipitating the 3 steps of carcinogenesis, that is, its initiation, promotion, and progression.6 Free radicals and reactive oxygen species (ROS) generated by environmental carcinogens, or by metabolic alterations, cause DNA damage and genetic instability. [6][7][8] DNA damage induced by oxidative stress is the major contributor to the development of malignancy. It is wellknown that natural antioxidant defenses are active in counteracting the production of free radicals and the molecular damage inflicted by them on DNA and other C ancer is a major health problem in industrialized and developing countries. Most diagnoses of cancer occur in people more than 55 years of age, with prostate cancer being the leading type of cancer in males followed by lung cancer. In females, breast and colon cancers are the leading types of cancer. Melatonin is a phylogenetically well-preserved molecule with diverse physiological functions. In addition to its well-known regulatory control of the sleep/wake cycle, as well as circadian rhythms generally, melatonin is involved in immunomodulation, hematopoiesis, and antioxidative processes. Recent human and animal studies have now shown that melatonin also has important oncostatic properties. Both at physiological and pharmacological doses melatonin exerts growth inhibitory effects on breast cancer cell lines. In hepatomas, through its activation of MT 1 and MT 2 receptors, melatonin inhibits linoleic acid uptake, thereby preventing the formation of the mitogenic metabolite 1,3-hydroxyoctadecadienoic acid. In animal model studies, melatonin has been shown to have preventative action against nitrosodiethylamine (NDEA)-induced liver cancer. Melatonin also inhibits the growth of prostate tumors via activation of MT 1 receptors thereby inducing translocation of the androgen receptor to the cytoplasm and inhibition of the effect of endogenous androgens. There is abundant evidence indicating that melatonin is involved in preventing tumor initiation, promotion, and progression. The anticarcinogenic effect of melatonin on neoplastic cells relies on its antioxidant, immunostimulating, and apoptotic properties. Melatonin's oncostatic actions include the direct augmentation of natural killer (NK) cell activity, which increases immunosurveillance, as well as the stimulation of cytokine production, for example, of interleukin (IL)-2, IL-6, IL-12, and interferon (IFN)-γ. In addition to its direct oncostatic action, melatonin protects hematopoietic precursors from the toxic effect of anticancer chemotherapeutic drugs. Melatonin secretion...

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“…In CRC, melatonin inhibits cell growth and induces apoptosis in vitro [21,22,23] and in vivo [24]. Recently, it has been reported that melatonin decreases CSCs and dysplastic injuries in colon tissue [24].…”

Section: Introductionmentioning

confidence: 99%

AA-NAT, MT1 and MT2 Correlates with Cancer Stem-Like Cell Markers in Colorectal Cancer: Study of the Influence of Stage and p53 Status of Tumors

Casado

Iñigo-Chaves

Jiménez-Ruiz

et al. 2017

IJMS

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The characterization of colon cancer stem cells (CSCs) may help to develop novel diagnostic and therapeutic procedures. p53 loss increases the pool of CSCs in colorectal cancer (CRC). Recent reports suggest that the oncostatic effects of melatonin could be related to its ability to kill CSCs. Although there are no data linking the loss of p53 function and melatonin synthesis or signaling in cancer, melatonin does activate the p53 tumor-suppressor pathway in this disease. In this work, we analyze whether the expression of melatonin synthesis and signaling genes are related to the expression of CSC markers and the implication of p53 status in samples from patients with CRC. Arylalkylamine N-acetyltransferase (AA-NAT), MT1, and MT2 expression decreased in tumor samples versus normal mucosa samples in mutated p53 (mtp53) tumors versus those with wild-type p53 (wtp53). Further, AA-NAT and MT2 expression were lower in advanced stages of the disease in wtp53 tumors. On the contrary, CD44 and CD66c expression was higher in tumor versus normal mucosa in wtp53 tumors. Additionally, CD44 expression was higher in advanced stages of the disease regardless of the p53 status. Patients with CD44highCD66chigh and wtp53 tumors in advanced stages showed low expression of AA-NAT and MT2 in wtp53 tumors. These results could indicate a possible interaction of these pathways in CRC.

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In vitro effects of melatonin on cell proliferation in a colon adenocarcinoma line

Cited by 79 publications

References 18 publications

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review

Molecular mechanisms of the pro-apoptotic actions of melatonin in cancer: a review

Therapeutic Actions of Melatonin in Cancer: Possible Mechanisms

AA-NAT, MT1 and MT2 Correlates with Cancer Stem-Like Cell Markers in Colorectal Cancer: Study of the Influence of Stage and p53 Status of Tumors

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