Melatonin synergistically enhances cisplatin‐induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK‐OV‐3 cells

Kim, Jihyun; Jeong, Soo‐Jin; Kim, Bonglee; Yun, Sun-Mi; Choi, Do Young; Kim, Sung Hoon

doi:10.1111/j.1600-079x.2011.00935.x

Cited by 86 publications

(87 citation statements)

References 54 publications

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“…The findings of Kim et al [228] are consistent with the potential utility of melatonin’s use as a strategy to inhibit ovarian cancer. This group reported that combining cisplatin and melatonin caused a synergistic inhibitory effect on the viability of ovarian cancer cells (SK-OV-3) while melatonin, as reported elsewhere as well, protected normal ovarian cells from cisplatin-mediated cytotoxicity.…”

Section: Melatonin and Cancer Progressionsupporting

confidence: 57%

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Reíter

Rosales-Corral

Tan

et al. 2017

IJMS

376

368

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There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.

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Section: Melatonin and Cancer Progressionsupporting

confidence: 57%

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Reíter

Rosales-Corral

Tan

et al. 2017

IJMS

376

368

View full text Add to dashboard Cite

show abstract

“…The effects of melatonin on cell proliferation and apoptosis have been studied in vitro, basically using the serous papillary human OC cell line (SKOV-3) [31]. In pharmacological concentrations (0.5–2 mM), melatonin induced caspase-3 activation and cleavage of poly-(ADP-ribose) polymerase (PARP), resulting in the control of MAPK (Mitogen Activated Protein Kinase) phosphorylation.…”

Section: Discussionmentioning

confidence: 99%

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

Zonta

Martinez

Camargo

et al. 2017

IJMS

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Angiogenesis is a hallmark of ovarian cancer (OC); the ingrowth of blood vessels promotes rapid cell growth and the associated metastasis. Melatonin is a well-characterized indoleamine that possesses important anti-angiogenic properties in a set of aggressive solid tumors. Herein, we evaluated the role of melatonin therapy on the angiogenic signaling pathway in OC of an ethanol-preferring rat model that mimics the same pathophysiological conditions occurring in women. OC was chemically induced with a single injection of 7,12-dimethylbenz(a)anthracene (DMBA) under the ovarian bursa. After the rats developed serous papillary OC, half of the animals received intraperitoneal injections of melatonin (200 µg/100 g body weight/day) for 60 days. Melatonin-treated animals showed a significant reduction in OC size and microvessel density. Serum levels of melatonin were higher following therapy, and the expression of its receptor MT1 was significantly increased in OC-bearing rats, regardless of ethanol intake. TGFβ1, a transforming growth factor-beta1, was reduced only after melatonin treatment. Importantly, vascular endothelial growth factor (VEGF) was severely reduced after melatonin therapy in animals given or not given ethanol. Conversely, the levels of VEGF receptor 1 (VEGFR1) was diminished after ethanol consumption, regardless of melatonin therapy, and VEGFR2 was only reduced following melatonin. Hypoxia-inducible factor (HIF)-1α was augmented with ethanol consumption, and, notably, melatonin significantly reduced their levels. Collectively, our results suggest that melatonin attenuates angiogenesis in OC in an animal model of ethanol consumption; this provides a possible complementary therapeutic opportunity for concurrent OC chemotherapy.

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“…ELISA was employed to verify the LH serum level ~30 U/l in mice treated with LH, which is comparable to the LH level in patients with post-menopausal ovarian cancer (29). Cisplatin is capable of inducing apoptosis in ovarian cancer cells (30,31). In the present study, cisplatin significantly inhibited the growth of ovarian tumors, number of tumor nodules and volume of ascites.…”

Section: Discussionmentioning

confidence: 72%

Luteinizing hormone compromises the inï¿½vivo anti-tumor effect of cisplatin on human epithelial ovarian cancer cells

et al. 2017

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Abstract. Platinum-based chemotherapy is the most common therapeutic regimen used to treat patients with ovarian cancer. However, the emergence of drug resistance to platinum compromises the clinical success of this treatment. Epithelial ovarian cancer is usually accompanied by an increased level of luteinizing hormone (LH). Therefore, the effect of LH on platinum resistance requires further investigation. In the current study, the effect of cisplatin and/or LH on platinum resistance was examined using the SKOV3ip1 and HeyA8 models. Following therapy, tumors were examined for proliferation (ki67) and apoptosis (cleaved caspase-3). Cisplatin alone and in combination with LH significantly inhibited tumor growth in SKOV3ip1-and HeyA8-implanted mice. Treatment with LH alone had minimal effect in the models. However, treatment with cisplatin combined with LH was less effective than treatment with cisplatin alone. Additionally, ki67 counts were significantly increased and cleaved caspase-3 counts were significantly reduced in mice treated with cisplatin combined with LH compared with mice treated with cisplatin alone. Such results indicate that LH weakens the anti-tumor effect of cisplatin in vivo and that LH may contribute to the development of drug resistance to cisplatin in ovarian cancer.

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Melatonin synergistically enhances cisplatin‐induced apoptosis via the dephosphorylation of ERK/p90 ribosomal S6 kinase/heat shock protein 27 in SK‐OV‐3 cells

Cited by 86 publications

References 54 publications

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Melatonin, a Full Service Anti-Cancer Agent: Inhibition of Initiation, Progression and Metastasis

Melatonin Reduces Angiogenesis in Serous Papillary Ovarian Carcinoma of Ethanol-Preferring Rats

Luteinizing hormone compromises the inï¿½vivo anti-tumor effect of cisplatin on human epithelial ovarian cancer cells

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