Cysteine Proteases from V. cundinamarcensis (C. candamarcensis) Inhibit Melanoma Metastasis and Modulate Expression of Proteins Related to Proliferation, Migration and Differentiation

Abstract

Previous studies showed that P1G10, a proteolytic fraction from Vasconcellea cundinamarcensis latex, reduced the tumor mass in animals bearing melanoma, increased in vitro DNA fragmentation and decreased cell adhesion. Here, we present some molecular and cellular events related to the antimetastatic effect induced by the CMS-2 fraction derived from P1G10 in metastatic melanoma B16-F10 and melanocyte Melan-a. Using difference gel electrophoresis and mass spectrometry, we identified four proteins overexpressed in tumor cells, all of them related to proliferation, survival, migration and cell invasion, that had their expression normalized upon treatment with CMS-2: nucleophosmin 1, heat shock protein 65, calcyclin binding protein and eukaryotic translation initiation factor 4H. In addition, some antioxidant and glycolytic enzymes show increased expression after exposure to CMS-2, along with an induction of melanogenesis (differentiation marker). The down regulation of cofilin 1, a protein involved in cell motility, may explain the inhibition of cell migration and dendritic-like outgrowth in B16-F10 and Melan-a, observed after CMS-2 treatment. Taken together, it is argued that CMS-2 modulates the expression of proteins related to metastatic development, driving the cell to a more differentiated-like state. These effects support the CMS-2 antimetastatic activity and place this fraction in the category of anticancer agent.

Insights from DOCK2 in cell function and pathophysiology

“…It is more likely than other types of skin cancer to invade nearby tissues and spread to other parts of the body. The key molecular and underlying mechanisms of the development and metastasis of melanoma are still poorly understood ( Lemos et al, 2018 ; Xu et al, 2019 ). A recent study has revealed that DOCK2 plays an important role in the malignant development of tumors by regulating melanoma stem cell activity.…”

Southern Species From the Biodiversity Hotspot of Central Chile: A Source of Color, Aroma, and Metabolites for Global Agriculture and Food Industry in a Scenario of Climate Change

“…On the other hand, the fraction called P1G10 has been used for gastric ulcers and diabetic foot treatments in several wounded models (Tonaco et al, 2018). At the same time, the reduction of tumour mass in animals bearing melanoma and metastasis level was observed using this fraction (Lemos et al, 2018).…”

Differential biological activity of two extracts of ripe fruits of Carica candamarcensis Hook on human neutrophils

“…Mello et al (2008), revealed that enzymes from the P1G10 proteolytic fraction of the fruit exert a protective and reconstructive role in gastric tissue, which is mediated by an increase in mucus content and a stimulation of mitosis to recover gastric ulcer lesions. Alburquerque et al (2020), found that the same Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas/ 292 fraction has an anti-inflammatory effect, and Lemos et al (2018), showed that it is able to inhibit metastasis in melanoma and helps to modulate the expression of proteins related to cell proliferation, migration, and differentiation.…”