Influence of Chronic Melatonin on 9,10-Dimethyl-1,2-Benzanthracene-Induced Mammary Tumors in Female Holtzman Rats Exposed to Continuous Light

Kothari, Lalita S.

doi:10.1159/000226445

Cited by 20 publications

(12 citation statements)

References 6 publications

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“…The decreased level of prolactin, estradiol, lipid peroxides following Mel, NS and RA administration agrees with previous studies (Kothari 1987; Blask et al . 1991; Abou‐Issa et al .…”

Section: Discussionsupporting

confidence: 93%

The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model

El-Aziz

Hassan

Mohamed

et al. 2005

Int J Experimental Path

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Worldwide, breast cancer is the second leading cause of cancer death among women and the third most common cancer. Although our understanding of the molecular basis of this fatal disease has improved, this malignancy remains elusive. Melatonin (Mel), retinoic acid (RA) and Nigella sativa (NS) are substances with anticancer effects. To date, our understanding of the mechanisms of therapeutic effects of these products in mammary cancer is still marginal. To look at the preventive and therapeutic values of these products, we carried out this investigation. An animal model formed of 80 rats was established. The animals were divided into eight groups of 10 animals each: (a) control group injected with the same vehicle used for treatments in the relevant dosages and routes; (b) carcinogen group injected with the known carcinogenic substance 7,12-di-methylbenz(a)anthracene (DMBA) that induces mammary carcinoma; (c) three prophylactic (Pro) groups (Mel-Pro, RA-Pro and NS-Pro) injected with test substances (Mel, RA and NS, respectively) 14 days before the intake of the carcinogenic substance DMBA and then continued until the end of the experiments; and (d) three treated (Tr) groups (Mel-Tr, RA-Tr and NS-Tr) injected with the vehicles after the intake of DMBA. In both the Pro and Tr groups, the drugs were daily administered for 3 months. The animals were killed, and their serum and tissues were evaluated for (a) markers of tumorigenicity [serum levels of total sialic acid (TSA) and lipid-bound sialic acid (LSA)], (b) markers of endocrine derangement (serum prolactin, estradiol and progesterone levels), (c) apoptotic changes [serum tumour necrosis factor (TNF)-alpha, tissue caspase-3 activity, percentage of DNA fragmentation and ultrastructural features of apoptosis] and (d) markers of oxidative stress (tissue levels of lipid peroxides and nitric oxide). Carcinoma was absent both in the control and in the NS-Pro groups. Mammary carcinoma occurred in DMBA and other Pro and Tr groups. The frequency of mammary carcinoma was high in the carcinogen DMBA group (60%), followed by the Tr (56%) and finally the Pro groups (33%). These tumours included papillary, comedo and cribriform carcinomas. As compared with the control group, the development of carcinoma in the carcinogen DMBA group was associated with increased levels of (a) markers of tumorigenicity (77.0 +/- 3.3 vs. 209.0 +/- 5.6 and P < 0.05 for TSA; 28.7 +/- 1.7 vs. 41.8 +/- 1.2 and P < 0.01 for LSA), (b) markers of endocrine derangement (2.5 +/- 0.1 vs. 3.6 +/- 0.3 and P < 0.05 for prolactin; 39.6 +/- 1.3 vs. 24.8 +/- 2.1 and P < 0.01 for progesterone and 31.0 +/- 0.7 vs. 51.1 +/- 3.4 and P < 0.01 for estradiol) and (c) markers of oxidative stress (2.3 +/- 0.2 vs. 5.2 +/- 0.7 and P < 0.01 for lipid peroxides and 4.4 +/- 0.2 vs. 7.6 +/- 0.8 and P < 0.01 for nitric oxide). Also, it was associated with decreased levels of markers of apoptotic activity (20.8 +/- 1.1 vs. 13.4 +/- 0.7 and P < 0.01 for caspase-3; 29.0 +/- 1.7 vs. 20.9 +/- 1.3 and P < 0.05 for percentage of DNA fr...

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“…The decreased level of prolactin, estradiol, lipid peroxides following Mel, NS and RA administration agrees with previous studies (Kothari 1987; Blask et al . 1991; Abou‐Issa et al .…”

Section: Discussionsupporting

confidence: 93%

The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model

El-Aziz

Hassan

Mohamed

et al. 2005

Int J Experimental Path

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“… suggested that high‐dose (300 mg/day = 5 mg/kg) melatonin delayed disease progression and extended survival through the reduction in oxidative damage in patients with amyotrophic lateral sclerosis. In addition, oral administration of melatonin (100 µ g/day/rat) via drinking water suppressed 7,12‐dimethylbenzanthracene‐induced mammary tumor growth . A number of clinical and basic studies are required to establish the optimal clinical dose of melatonin in certain cancers.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and post‐translational regulation of Bim controls apoptosis in melatonin‐treated human renal cancer Caki cells

Park

Woo

Min

et al. 2013

Journal of Pineal Research

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Melatonin (N-acetyl-5-methoxytryptamine) has recently gained attention as an anticancer agent and for combined cancer therapy. In this study, we investigated the underlying molecular mechanisms of the effects of melatonin on cancer cell death. Treatment with melatonin induced apoptosis and upregulated the expression of the pro-apoptotic protein Bcl-2-interacting mediator of cell death (Bim) in renal cancer Caki cells. Furthermore, downregulation of Bim expression by siRNA markedly reduced melatonin-mediated apoptosis. Melatonin increased Bim mRNA expression through the induction of Sp1 and E2F1 expression and transcriptional activity. We found that melatonin also modulated Bim protein stability through the inhibition of proteasome activity. However, melatonin-induced Bim upregulation was independent of melatonin's antioxidant properties and the melatonin receptor. Taken together, our results suggest that melatonin induces apoptosis through the upregulation of Bim expression at the transcriptional level and at the post-translational level.

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“…They found that melatonin reduced the number of tumors per rat in the ascending and descending colon when induced by DMH. Oral administration of melatonin via the drinking water was also reported to be effective in suppressing 7,12‐dimethylbenz(a)anthracene‐induced mammary tumor growth [119]. Finally, melatonin treatment induced apoptotic death in LNCaP cells via modulation of the p38 and JNK pathways [28].…”

Section: Melatonin’s Connection With Aging and Cancermentioning

confidence: 99%

Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer

Jung-Hynes

Reíter

Ahmad

2009

Journal of Pineal Research

204

151

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: Histone deacetylases (HDAC) have been under intense scientific investigation for a number of years. However, only recently the unique class III HDAC, sirtuins, have gained increasing investigational momentum. Originally linked to longevity in yeast, sirtuins and more specifically, SIRT1 have been implicated in numerous biological processes having both protective and/or detrimental effects. SIRT1 appears to play a critical role in the process of carcinogenesis, especially in age‐related neoplasms. Similarly, alterations in circadian rhythms as well as production of the pineal hormone melatonin have been linked to aging and cancer risk. Melatonin has been found act as a differentiating agent in some cancer cells and to lower their invasive and metastatic status. In addition, melatonin synthesis and release occurs in a circadian rhythm fashion and it has been linked to the core circadian machinery genes (Clock, Bmal1, Periods, and Cryptochromes). Melatonin has also been associated with chronotherapy, the timely administration of chemotherapy agents to optimize trends in biological cycles. Interestingly, a recent set of studies have linked SIRT1 to the circadian rhythm machinery through direct deacetylation activity as well as through the nicotinamide adenine dinucleotide (NAD+) salvage pathway. In this review, we provide evidence for a possible connection between sirtuins, melatonin, and the circadian rhythm circuitry and their implications in aging, chronomodulation, and cancer.

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Influence of Chronic Melatonin on 9,10-Dimethyl-1,2-Benzanthracene-Induced Mammary Tumors in Female Holtzman Rats Exposed to Continuous Light

Cited by 20 publications

References 6 publications

The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model

The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma: an animal model

Transcriptional and post‐translational regulation of Bim controls apoptosis in melatonin‐treated human renal cancer Caki cells

Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer

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