Antitumor‑ and apoptosis‑inducing effects of pomolic acid against SK‑MEL‑2 human malignant melanoma cells are mediated via inhibition of cell migration and sub‑G1 cell cycle arrest

MicroRNAs regulate gene expression by repressing translation or directing sequence-specific degradation of their complementary mRNA. We recently reported that miR-203 is down-regulated, and its exogenous expression inhibits cell growth in canine oral malignant melanoma tissue specimens as well as in canine and human malignant melanoma cells. A microRNA target database predicted E2F3 and ZBP-89 as putative targets of microRNA-203 (miR-203). The expression levels of E2F3a, E2F3b, and ZBP-89 were markedly up-regulated in human malignant melanoma Mewo cells compared with those in human epidermal melanocytes. miR-203 significantly suppressed the luciferase activity of reporter plasmids containing the 3′-UTR sequence of either E2F3 or ZBP-89 complementary to miR-203. The ectopic expression of miR-203 in melanoma cells reduced the levels of E2F3a, E2F3b, and ZBP-89 protein expression. At the same time, miR-203 induced cell cycle arrest and senescence phenotypes, such as elevated expression of hypophosphorylated retinoblastoma and other markers for senescence. Silencing of E2F3, but not of ZBP-89, inhibited cell growth and induced cell cycle arrest and senescence. These results demonstrate a novel role for miR-203 as a tumor suppressor acting by inducing senescence in melanoma cells.

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15792 β3-Tubulin knockdown impairs microtubule dynamics, induces cell cycle arrest, and decreases the spontaneous release of microvesicles in human skin malignant melanoma cells (A375)

Journal of the American Academy of Dermatology ◽

10.1016/j.jaad.2020.06.727 ◽

2020 ◽

Vol 83 (6) ◽

pp. AB160

Author(s):

Philip Surmanowicz ◽

Mohammed Omar Altonsy ◽

Anutosh Ganguly ◽

Gilles J. Lauzon ◽

P. Régine Mydlarski

Keyword(s):

Cell Cycle ◽

Malignant Melanoma ◽

Cell Cycle Arrest ◽

Human Skin ◽

Melanoma Cells ◽

Microtubule Dynamics ◽

Spontaneous Release ◽

Cycle Arrest

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In Vitro Anticancer Effects of All-trans Retinoic Acid in Combination with Dacarbazine against CD117+ Melanoma Cells

Drug Research ◽

10.1055/a-1240-0072 ◽

2020 ◽

Vol 70 (12) ◽

pp. 563-569

Author(s):

Bahareh Mohammadi Jobani ◽

Elham Mohebi ◽

Nowruz Najafzadeh

Keyword(s):

Cell Cycle ◽

Retinoic Acid ◽

Malignant Melanoma ◽

Cell Cycle Arrest ◽

Combined Treatment ◽

Melanoma Cells ◽

Cycle Arrest ◽

Trans Retinoic Acid ◽

All Trans Retinoic Acid

Abstract Background Malignant melanoma is a common form of skin cancer that contains different cell types recognized by various cell surface markers. Dacarbazine-based combination chemotherapy is frequently used for the treatment of melanoma. Despite its potent anticancer properties, resistance to dacarbazine develops in malignant melanoma. Here, we aim to improve response to dacarbazine therapy by pretreatment with all-trans retinoic acid (ATRA) in CD117+ melanoma cells. Methods The CD117+ melanoma cells were sorted from A375 malignant melanoma cell line using magnetic-activated cell sorting (MACS). The cell viability was examined by cell proliferation assay (MTT). Apoptosis was determined by acridine orange/ ethidium bromide staining. Indeed, we performed flow cytometry to evaluate the cell cycle arrest. Results Here, the CD117+ melanoma cells were incubated with various concentrations of ATRA, dacarbazine, and their combination to determine IC50 values. We found that 20 µM ATRA treatment followed by dacarbazine was found to be more effective than dacarbazine alone. There was an indication that the combination of ATRA with dacarbazine (ATRA/dacarbazine) caused more apoptosis and necrosis in the melanoma cells (P<0.05). Furthermore, ATRA/dacarbazine treatment inhibited the cell at the G0/G1 phase, while dacarbazine alone inhibited the cells at S phase. Conclusion Collectively, combined treatment with ATRA and dacarbazine induced more apoptosis and enhanced the cell cycle arrest of CD117+ melanoma cells. These results suggested that ATRA increased the sensitivity of melanoma cells to the effect of dacarbazine.

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