β-Lapachone suppresses the lung metastasis of melanoma via the MAPK signaling pathway

Kee, Ji Ye; Han, Yo Han; Kim, Dae Seung; Mun, Jeong Geon; Park, Seong Hwan; So, Hong Seob; Park, Sung Joo; Park, Raekil; Um, Jae Young; Hong, Seongin

doi:10.1371/journal.pone.0176937

Cited by 20 publications

(14 citation statements)

References 37 publications

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“…The metastatic spread of the primary lesion is the worst scenario when dealing with melanoma. In fact, melanoma is the most aggressive skin malignancy, giving rise to lung and brain metastasis in most of the patients suffering from distant lesions [ 29 , 30 ]. To study the antitumor effect of Ocoxin, we analyzed the lung metastasis of YUMM-1.7 melanoma upon different treatment routines.…”

Section: Resultsmentioning

confidence: 99%

Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma

et al. 2021

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Whereas the prevalence of several cancer types is decreasing, skin malignancies are growing more common every year. Malignant melanoma is the most aggressive form of skin cancer with high metastatic capacity. In most cases, malignant melanoma shows acquired therapy resistance. We evaluated the ability of Ocoxin, a natural compound-based antioxidant and anti-inflammatory nutritional complement, to exert an antitumor effect in melanoma. To do so, the cytotoxicity of Ocoxin in a panel of BRAF-mutated murine and human melanoma cell lines was tested alone and in combination with BRAF inhibitor Vemurafenib. Our results revealed a potent cytotoxic effect of Ocoxin against melanoma cells and a synergic effect when combined with Vemurafenib, reducing viability and increasing apoptosis. Besides, Ocoxin interferes with the cell cycle, impairs the inherent and fibroblast-mediated melanoma cell migration, and reduces resistance to BRAF inhibition. Proteomic analysis revealed reduced tumor secretion of inflammatory factors Galectin-1, Osteopontin, CCL5, and CCL9 upon treatment with Ocoxin. Moreover, RNASeq showed that Ocoxin downregulated the cell cycle and proliferation-related genes. In vivo, Ocoxin reduced the number of lung metastasis of YUMM-1.7 melanoma cells. Therefore, Ocoxin arises as a good candidate for clinical trials analyzing the beneficial effects in patients suffering from this cutaneous malignancy.

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Section: Resultsmentioning

confidence: 99%

Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma

et al. 2021

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“…Murine Bl6-F10 cells were established from lung metastasis of B16-F0 cells by i.v. injection through 10 successive selections and are usually employed to investigate the anti-metastatic effects of different compounds (Fidler, 1973;Mummert et al, 2003;Chien et al, 2015;Kee et al, 2017). The interaction of melanoma cells with extracellular matrix proteins is one of the initial steps crucial for metastatic dissemination and we found that TAP7f inhibited cell adhesion to the immobilized matrix proteins vitronectin and fibronectin.…”

Section: Discussionmentioning

confidence: 65%

A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway

et al. 2020

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The synthetic triazolylpeptidyl penicillin derivative, named TAP7f, has been previously characterized as an effective antitumor agent in vitro and in vivo against B16-F0 melanoma cells. In this study, we investigated the anti-metastatic potential of this compound on highly metastatic murine B16-F10 and human A375 melanoma cells. We found that TAP7f inhibited cell adhesion, migration and invasion in a dose-dependent manner. Additionally, we demonstrated that TAP7f downregulated integrin avb3 expression and Wnt/b-catenin pathway, a signaling cascade commonly related to tumor invasion and metastasis. Thus, TAP7f reduced both the enzymatic activity and the expression levels of matrixmetalloproteinases-2 and-9 in a time dependent manner. Moreover, TAP7f inhibited the expression of the transcription factor Snail and the mesenchymal markers vimentin, and N-cadherin, and up-regulated the expression of the epithelial marker E-cadherin, suggesting that the penicillin derivative affects epithelial-mesenchymal transition. Results obtained in vitro were supported by those obtained in a B16-F10-bearing mice metastatic model, that showed a significant TAP7f inhibition of lung metastasis. These findings suggest the potential of TAP7f as a chemotherapeutic agent for the treatment of metastatic melanoma.

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“…Thus, PEITC and BITC may affect cell migration and invasion of A375.S2 cells via MAPK pathway. MAPK pathway regulated cellular invasion and metastasis (49) and suppression of MAPK pathway could prevent cancer's invasion and metastasis including in melanoma (50,51).…”

Section: Discussionmentioning

confidence: 99%

Phenethyl Isothiocyanate (PEITC) and Benzyl Isothiocyanate (BITC) Inhibit Human Melanoma A375.S2 Cell Migration and Invasion by Affecting MAPK Signaling Pathway In Vitro

2017

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Abstract. Background/Aim: Numerous evidence has shown that PEITC and BITC inhibit cancer cell migration and invasion. In this study, we investigated the anti-metastatic mechanisms of PEITC and BITC in human melanomaSkin cancer is one of the most common malignant neoplasms in the white population. Melanoma is much more common in whites than in other ethnic groups (1). In USA, the incidence of melanoma is the fifth and seventh most common cancer among men and women, respectively (2). Worldwide, the incidence rate of melanoma skin cancer is increasing (3). At ages over the age of 75 years old, the incidence rate is almost three times higher in males than that in females (4, 5). In the past years, metastatic melanomas have been increased and led to a high rate of death 6223

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β-Lapachone suppresses the lung metastasis of melanoma via the MAPK signaling pathway

Cited by 20 publications

References 37 publications

Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma

Ocoxin Increases the Antitumor Effect of BRAF Inhibition and Reduces Cancer Associated Fibroblast-Mediated Chemoresistance and Protumoral Activity in Metastatic Melanoma

A Penicillin Derivative Exerts an Anti-Metastatic Activity in Melanoma Cells Through the Downregulation of Integrin αvβ3 and Wnt/β-Catenin Pathway

Phenethyl Isothiocyanate (PEITC) and Benzyl Isothiocyanate (BITC) Inhibit Human Melanoma A375.S2 Cell Migration and Invasion by Affecting MAPK Signaling Pathway In Vitro

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