Melatonin promotes ATO-induced apoptosis in MCF-7 cells: Proposing novel therapeutic potential for breast cancer

Published on Friday, 22 July 2016


Arsenic trioxide (ATO), a traditional Chinese medicine, has long been of biomedical interest and is largely used for treatment of a broad spectrum of cancers.

Melatonin, a naturally occurring indoleamine synthesized in the pineal gland, has been considered as a biomarker for endocrine-dependent tumors, particularly breast cancer.

An increasing number of studies indicate that melatonin could be an attractive candidate for combined therapy due to its anti-oxidant and cytotoxic activities.

The aim of this study was to investigate the potentiating effect of melatonin on ATO-induced apoptosis in estrogen receptor (ER)-positive breast cancer cell line, MCF-7. Our data highlighted for the first time that pre-treating MCF-7 cells with physiological concentration of melatonin substantially augmented the cytotoxic effects of ATO as compared with either agent alone.

Real-time PCR analysis revealed that apoptosis induction by the drugs combination was associated with increased p53 transcriptional activity followed by the elevated molecular ratio of Bax/Bcl-2. Moreover, induced p21, subsequent G1 cell cycle arrest and transcriptional suppression of survivin-mediated c-Myc and hTERT expression may contribute in the enhanced growth suppressive effect of ATO-plus-melatonin.

Due to the safety profile of melatonin, our study suggests that using melatonin in combination with ATO might provide insight into a novel adjuvant therapy and may confer advantages for breast cancer treatment.



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See also:

- About Melatonin;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma.