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Oncostatic Effects of Melatonin in Breast Cancer: A Review

1
Neha Roy , Prerona Saha 1⃰
1Guru Nanak Institute of Pharmaceutical Science and Technology

157/F Nilgunj Road, Panihati, Sodepur, Kolkata-700114, West Bengal, India

1⃰ Email: prerona.saha@gnipst.ac.in

Introduction Clinical Studies

Melatonin (MLT) is an active neuroendocrine hormone secreted from the pineal gland mainly during the night and is primarily known to Numerous clinical studies reported that administration of melatonin as an adjuvant molecule along with the conventional anticancer
regulate the human wake and sleep cycle [1]. Besides, the pineal hormone has attributed to many other physiological roles as an antioxidant & drugs and/or immunotherapy not only help reduce the adverse effects of the later, but also enhance their therapeutic efficacy [4].
free-radical scavenger [2], immunomodulator [3], etc. In the recent years, MLT has emerged increasingly as a potent molecule to treat cancer. Melatonin Analogues Used in Breast Cancer
When administered along with the conventional chemotherapeutic drugs, it exerted oncostatic effects in both, hormone-dependent as well as
hormone-independent cancers by altering various signalling cascades [1]. UCM 976 UCM
1033
MELATONIN
ANALOGOUES
Objective UCM 1032 UCM 1037

This review aims to summarize the oncostatic effects of melatonin (and its analogues) in breast cancer, based on experimental and clinical
studies.
Effects of Melatonin Analogues in Breast Cancer Cells
Mechanism of Action of Melatonin in Breast Cancer
EFFECT OF MELATONIN ANALOGUES ON MCF -7 CELLS EFFECT OF MELATONIN ANALOGUES ON MDA -MB231
120 120

% CELL VIABILITY VS DMSO

% CELL VIABILITY VS DMSO

100 100

80
80

Antiproliferative Apoptotic 60

40
60

40
20
20
0
DMSO (0.1%) Melatonin UCM 976 UCM 1032 UCM 1033 UCM 1037 0

Melatonin
DMSO (0.1%) Melatonin UCM 976 UCM 1032 UCM 1033 UCM 1037
RESPONSE AT CONC. 10-5-10-3M
(AFTER 72 HOURS) RESPONSE AT CONC. 10-5-10-3M
(AFTER 72 HOURS)

Pros & Cons of Melatonin in Breast Cancer

Minor side-effects,
Melatonin exerts like headache,
oncostatic properties on

Antiangiogenic Antiaromatase many cancers (hormone-

dependent/independent
diziness, nausea
and apathy
combined with

CONS
PROS
[4].
weight gain may
Decreases the side- be observed [8].
effects of anticancer
drugs and increases their
therapeutic efficacy [6].
Has low toxicity levels;
no major side-effects [7].

•Antiproliferative effect: On ER(+) tumours, providing a high expression of the MT1 receptors. Future Prospects of Melatonin to Combat Breast Cancer [4]
•Induction of Apoptosis: By modulation of the COX-2/PGE2, p300/NF-κb and Akt signalling pathway, and Apaf-1/caspase-dependent
➢ Molecular mechanism(s) of melatonin’s oncostatic actions should be further investigated.
apoptotic pathway
➢ For clinical trials, melatonin’s enhancing effect on more anticancer drugs should be assessed.
•Antiangiogenic effect: By decreasing the levels of HIF-1α protein in the human breast cancer cell lines, and VEGF around the endothelial
cells. ➢ Its direct effect on patients with manifest cancer should be studied by exogeneous melatonin administration to find its oncostatic
Anti-aromatase activity: By downregulation of the anti-adipogenic cytokines, thereby decreasing the number of estrogen producing cells as well as long-term effects on other cancers.
proximal to malignant cells. Conclusion
Researches gathered from various scientific literatures provided the beneficial outcomes of melatonin as an adjuvant therapy in
Methods Used to Study Melatonin’s Effects in Breast Cancer
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combating breast cancer and exhibiting potential anticarcinogenic activities. Thus, a molecule which was initially understood just as
Table: In-vitro & In-vivo Effects of Melatonin in Breast Cancer[4]
the modulator of the human circadian rhythm, has now attained a remarkable spot in the oncological field as well.
Study Method Cell lines/ Object Response(s) Possible Mechanism of Action(s)
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