Abstract
β-Lapachone is a natural quinone compound from Lapacho trees, which has various pharmacological effects such as anti-bacterial, anti-fungal, anti-viral, and anti-inflammatory activities. However, the effect of β-lapachone on metastasis of melanoma cells is unclear. In this study, β-lapachone reduced cell viability of metastatic melanoma cancer cell lines B16F10 and B16BL6 through induction of apoptosis via the mitogen-activated protein kinase (MAPK) pathway. Additionally, flow cytometry results showed that β-lapachone increased DNA content in the G0/G1 phase of the cell cycle. Analysis of the mechanisms of these events indicated that β-lapachone regulated the expression of Bcl-2, Bcl-xL, and Bax, resulting in the activation of caspase-3, -8, -9, and poly-ADP-ribose polymerase (PARP). Moreover, the β-lapachone-administered group showed significantly decreased lung metastasis in the experimental mouse model. In conclusion, our study demonstrates the inhibitory effect of β-lapachone on lung metastasis of melanoma cells and provides a new insight into the role of β-lapachone as a potential antitumor agent.
Highlights
Melanoma is a highly aggressive cancer and is the leading cause of death from skin cancer because of its resistance against most conventional treatments and tendency to metastasize [1]
Using the WST assay, we found that β-lapachone exhibited cytotoxicity in metastatic melanoma cell lines B16F10 and B16BL6 in a time- and dose-dependent manner (Fig 1A and 1B)
To confirm that the inhibitory effect of β-lapachone on melanoma cell growth was partly due to cell cycle arrest, B16F10 cells were treated with various concentrations of β-lapachone for 24 h, and cell cycle analysis was performed using propidium iodide (PI) staining
Summary
Melanoma is a highly aggressive cancer and is the leading cause of death from skin cancer because of its resistance against most conventional treatments and tendency to metastasize [1]. Worldwide statistics show that melanoma incidence and mortality rates have been increasing for at least 30 years [2]. The prognosis for melanoma remains very poor, with a 5-year survival rate of less than 5% [3,4]. The most dangerous aspect of melanoma is its metastatic ability to spread to other organs such as the liver, lungs, brain, and bones in later stages [5]. New effective and safe therapeutic agents for metastatic melanoma are needed. Metastasis is caused by movement of cancer cells from the primary tumor to target organs. Cancer cell migration and invasion abilities are associated with metastasis.
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