Melatonin suppresses tumor progression by reducing angiogenesis stimulated by <scp>HIF</scp>‐1 in a mouse tumor model

Kim, Kil-Jung; Choi, Jae-Sun; Kang, In‐Cheol; Kim, Kyu‐Won; Jeong, Chul‐Ho; Jeong, Joo‐Won

doi:10.1111/j.1600-079x.2012.01030.x

Cited by 97 publications

(108 citation statements)

References 46 publications

(60 reference statements)

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“…To measure the angiogenic level of tumors, we measured the hemoglobin content of each tumor using Drabkin's reagent [24][25][26][27]. As shown in Fig.…”

Section: Ca Inhibits Tumor Angiogenesismentioning

confidence: 99%

Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1α expression during tumor progression

Bae

Choi

Kim

et al. 2015

Biochemical Pharmacology

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“…To measure the angiogenic level of tumors, we measured the hemoglobin content of each tumor using Drabkin's reagent [24][25][26][27]. As shown in Fig.…”

Section: Ca Inhibits Tumor Angiogenesismentioning

confidence: 99%

Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1α expression during tumor progression

Bae

Choi

Kim

et al. 2015

Biochemical Pharmacology

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“…However, many studies have indicated that tumor cells exposed to hypoxia are resistant to TRAIL-induced cancer cell apoptosis [14,26,27] and overcoming inhibition by hypoxia has been a target in solid tumor anticancer therapy using the TRAIL protein [28,29]. Melatonin possesses anti-angiogenic activity by inhibiting stabilization of HIF-1α in the HCT116 cell line [12,30]. …”

Section: Introductionmentioning

confidence: 99%

Overcoming Hypoxic-Resistance of Tumor Cells to TRAIL-Induced Apoptosis through Melatonin

Lee

Moon

Park

2014

IJMS

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A solid tumor is often exposed to hypoxic or anoxic conditions; thus, tumor cell responses to hypoxia are important for tumor progression as well as tumor therapy. Our previous studies indicated that tumor cells are resistant to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cell apoptosis under hypoxic conditions. Melatonin inhibits cell proliferation in many cancer types and induces apoptosis in some particular cancer types. Here, we examined the effects of melatonin on hypoxic resistant cells against TRAIL-induced apoptosis and the possible mechanisms of melatonin in the hypoxic response. Melatonin treatment increased TRAIL-induced A549 cell death under hypoxic conditions, although hypoxia inhibited TRAIL-mediated cell apoptosis. In a mechanistic study, hypoxia inducible factor-1α and prolyl-hydroxylase 2 proteins, which increase following exposure to hypoxia, were dose-dependently down-regulated by melatonin treatment. Melatonin also blocked the hypoxic responses that reduced pro-apoptotic proteins and increased anti-apoptotic proteins including Bcl-2 and Bcl-xL. Furthermore, melatonin treatment reduced TRAIL resistance by regulating the mitochondrial transmembrane potential and Bax translocation. Our results first demonstrated that melatonin treatment induces apoptosis in TRAIL-resistant hypoxic tumor cells by diminishing the anti-apoptotic signals mediated by hypoxia and also suggest that melatonin could be a tumor therapeutic tool by combining with other apoptotic ligands including TRAIL, particularly in solid tumor cells exposed to hypoxia.

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“…Melatonin may either promote (103) or inhibit (104) angiogenesis depending on the pathological situation. Melatonin inhibits tumor angiogenesis by lowering both basal and hypoxia-induced tumor-cell VEGF production (104)(105)(106). However, melatonin also promotes beneficial angiogenesis in ulcers (103) as well as during wound healing (107) and bone repair (108).…”

Section: Angiogenic Functions Of Circadian Factors or Output Moleculesmentioning

confidence: 99%

Circadian angiogenesis

Jensen¹,

Gyllenhaal

Block

2014

Biomolecular Concepts

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Daily rhythms of light/darkness, activity/rest and feeding/fasting are important in human physiology and their disruption (for example by frequent changes between day and night shifts) increases the risk of disease. Many of the diseases found to be associated with such disrupted circadian lifestyles, including cancer, cardiovascular diseases, metabolic disorders and neurological diseases, depend on pathological de-regulation of angiogenesis, suggesting that disrupting the circadian clock will impair the physiological regulation of angiogenesis leading to development and progression of these diseases. Today there is little known regarding circadian regulation of pathological angiogenesis but there is some evidence that supports both direct and indirect regulation of angiogenic factors by the cellular circadian clock machinery, as well as by circulating circadian factors, important for coordinating circadian rhythms in the organism. Through highlighting recent advances both in pre-clinical and clinical research on various diseases including cancer, cardiovascular disorders and obesity, we will here present an overview of the available knowledge on the importance of circadian regulation of angiogenesis and discuss how the circadian clock may provide alternative targets for pro- or anti-angiogenic therapy in the future.

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Melatonin suppresses tumor progression by reducing angiogenesis stimulated by HIF‐1 in a mouse tumor model

Cited by 97 publications

References 46 publications

Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1α expression during tumor progression

Cinnamic aldehyde suppresses hypoxia-induced angiogenesis via inhibition of hypoxia-inducible factor-1α expression during tumor progression

Overcoming Hypoxic-Resistance of Tumor Cells to TRAIL-Induced Apoptosis through Melatonin

Circadian angiogenesis

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