Antiangiogenesis, Loss of Cell Adhesion and Apoptosis Are Involved in the Antitumoral Activity of Proteases from V. cundinamarcensis (C. candamarcensis) in Murine Melanoma B16F1

Abstract

The proteolytic enzymes from V. cundinamarcensis latex, (P1G10), display healing activity in animal models following various types of lesions. P1G10 or the purified isoforms act as mitogens on fibroblast and epithelial cells by stimulating angiogenesis and wound healing in gastric and cutaneous ulcers models. Based on evidence that plant proteinases act as antitumorals, we verified this effect on a murine melanoma model. The antitumoral effect analyzed mice survival and tumor development after subcutaneous administration of P1G10 into C57BL/6J mice bearing B16F1 low metastatic melanoma. Possible factors involved in the antitumoral action were assessed, i.e., cytotoxicity, cell adhesion and apoptosis in vitro, haemoglobin (Hb), vascular endothelial growth factor (VEGF), tumor growth factor-β (TGF-β), tumor necrosis factor-α (TNF-α) content and N-acetyl-glucosaminidase (NAG) activity. We observed that P1G10 inhibited angiogenesis measured by the decline of Hb and VEGF within the tumor, and TGF-β displayed a non-significant increase and TNF-α showed a minor non-significant reduction. On the other hand, there was an increase in NAG activity. In treated B16F1 cells, apoptosis was induced along with decreased cell binding to extracellular matrix components (ECM) and anchorage, without impairing viability.

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

“…Our group recently showed that the proteolytic fraction P1G10 exerts antitumor activity by reducing tumor mass and increasing survival of mice bearing melanoma. The antitumoral activity of P1G10 was explained by its pro-apoptotic and anti-angiogenic effect, as well as by its ability to reduce cell adhesion to ECM [ 9 ]. Further fractionation of the 14 isoforms composing P1G10 was done by CMS-Sephadex chromatography to recover two major proteinase peaks (CMS-1 and CMS-2) and a smaller CMS-3 peak, with CMS-2 containing five of these isoforms [ 25 ].…”

“…We recently reported that P1G10 displays a remarkable antitumor activity in a murine melanoma model. The antitumor activity of P1G10 was supported by its pro-apoptotic and anti-angiogenic effect, in addition to its ability for reducing cell adhesion to extracellular matrix (ECM) [ 9 ].…”

Apoptozisin Biyokimyası

“…Bir transkripsiyon düzenleyici faktör olan Mdm-2 (murine double minute 2), ya p-53'ün transkripsiyonunu inhibe ederek ya da p-53'e bağlanarak aktivitesini inhibe eder. Diğer taraftan DNA'nın hasar görmesi durumunda, p-53'ün fosforilasyonu artar ve Mdm-2'den ayrılarak aktivitesi de artmış olur 10 .…”

Chrysin Inhibits Melanoma Tumor Metastasis via Interfering with the FOXM1/β-Catenin Signaling

“…By inhibiting integrin and focal adhesion kinase, researchers indicate that melanoma cells can be more sensitive to the anoikis, thereby suppressing melanoma metastasis. , The induction of angiogenesis is another critical point in melanoma metastasis. Melanoma stimulates blood vessel growth and induces angiogenesis responses in the body by secreting growth factors. , These growth factors interact with receptors for extracellular matrix (ECM), integrins, and matrix metalloproteinases (MMPs) to promote endothelial migration and proliferation …”