Melatonin inhibits human melanoma cells proliferation and invasion via cell cycle arrest and cytoskeleton remodeling
Melatonin Research(2020)
摘要
Among skin cancers,
melanoma has the highest mortality rate. The heterogeneous genetic melanoma
background leads to a tumor-propagating capacity particularly important in
maintaining therapeutic resistance, and tumor recurrence. The identification of
efficient molecules able to control melanoma progress represents an important
opportunity for new therapeutic strategies, particularly in combination with the
current standard-of-care treatments. In this context,
several studies have reported the antitumor effects of melatonin against
different types of cancer, including melanoma. Here,
we describe the underlying mechanisms associated with melatonin’s activity in
human melanoma cell lines, focusing on cell cycle and cytoskeleton
remodeling. Interestingly, while melatonin induced melanocyte
DNA replication, melanoma cells exhibited cell cycle arrest in the G1-phase.
This phenomenon was associated with cyclin-D1 downregulation or p21
overexpression. The efficacy of melatonin on melanoma cells survival and
proliferation was detected using the clonogenic assay, with a decrease in both
the number and size of colonies. Additionally, melatonin induced a dramatic
cytoskeleton remodeling in all melanoma cell lines, leading to a star-like
morphology or cell swelling. The role of melatonin on melanoma cytoskeleton was
associated with the actin disruption, with thinning and/or broken actin fibers,
and weak and/or loss of paxillin along stress fibers. These data support the
observed findings that melatonin impairs melanoma invasion in skin
reconstructed models. Together, our results suggest that melatonin could be
used to control melanoma growth and support basic and
clinical studies on melatonin as a promising immunometabolic
adjuvant for melanoma therapy.
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