Bauhinia variegata candida Fraction Induces Tumor Cell Death by Activation of Caspase-3, RIP, and TNF-R1 and Inhibits Cell Migration and Invasion In Vitro.

K M Santos,R C R Chagas,F E Pinto,R J Silva-Oliveira,I N F Gomes,R I M A Ribeiro,B G Oliveira,W Romão,R M V Reis

doi:10.1155/2018/4702481

Abstract

Metastasis remains the most common cause of death in cancer patients. Inhibition of metalloproteinases (MMPs) is an interesting approach to cancer therapy because of their role in the degradation of extracellular matrix (ECM), cell-cell, and cell-ECM interactions, modulating key events in cell migration and invasion. Herein, we show the cytotoxic and antimetastatic effects of the third fraction (FR3) from Bauhinia variegata candida (Bvc) stem on human cervical tumor cells (HeLa) and human peripheral blood mononuclear cells (PBMCs). FR3 inhibited MMP-2 and MMP-9 activity, indicated by zymogram. This fraction was cytotoxic to HeLa cells and noncytotoxic to PBMCs and decreased HeLa cell migration and invasion. FR3 is believed to stimulate extrinsic apoptosis together with necroptosis, assessed by western blotting. FR3 inhibited MMP-2 activity in the HeLa supernatant, differently from the control. The atomic mass spectrometry (ESI-MS) characterization suggested the presence of glucopyranosides, D-pinitol, fatty acids, and phenolic acid. These findings provide insight suggesting that FR3 contains components with potential tumor-selective cytotoxic action in addition to the action on the migration of tumor cells, which may be due to inhibition of MMPs.

Highlights

Cervical cancer (CC) is the fourth most frequent type of neoplasm among women in the worlds and the main cause of cancer-related death in low- and middle-income countries [1]
We observed that FR3 was the only fraction tested that completely inhibited MMP-2 and MMP-9 (Figure 1), standing out from the others
Active MMP-2 was not observed without supernatant from the treated cells in which the control cell supernatant showed a clear band corresponding to the activity of this enzyme (Figure 3(b))

Summary

Introduction

Cervical cancer (CC) is the fourth most frequent type of neoplasm among women in the worlds and the main cause of cancer-related death in low- and middle-income countries [1]. Human papilloma virus (HPV) is the main etiologic infectious agent associated with cervical cancer. 70% of cases of cervical cancer are induced by HPV types 16 and 18, but over 200 types of HPV have been identified [3]. HPV interferes with the cell cycle regulation because it infects the cervical mucosa and integrates its genome in cells. The viral E6 and E7 oncoproteins are critical for inducing malignant transformation because they lead to the suppression of p53 and pRB, fundamental tumor suppressor genes. Persistent infection leads to cervical intraepithelial neoplasia (CIN), which, if untreated, may progress to cancer cervical [4]

Methods

Results

Conclusion