Pomolic acid induces apoptosis and inhibits multidrug resistance protein MRP1 and migration in glioblastoma cells

Abstract

Glioblastoma (GBM), the most aggressive of primary brain tumors, determine short survival and poor quality of life. Therapies used for its treatment are not effective and chemotherapy failure is partially due to multidrug resistance (MDR) mechanisms present in the tumor cells. New therapeutic strategies are needed in order to improve survival in GBM. The present study investigated the activity of the pentacyclic triterpene pomolic acid (PA) in GBM. Pomolic acid decreased the viability and induced apoptosis of GBM cells as demonstrated by DNA fragmentation. It also induced uncoupling of mitochondria membrane potential and activation of caspase-3 and -9. Pomolic acid-induced apoptosis is dependent on reactive oxygen species (ROS) production as it is inhibited by anti-oxidant treatment. Pomolic acid also down-modulated the activity of the multidrug resistance associated protein 1 (MRP1) and inhibited migration of GBM cells. These results show that PA acts on several pathways of GBM drug resistance and therefore may be of potential interest for the treatment of this tumor.

Bioguided identification of pentacyclic triterpenoids as anti-inflammatory bioactive constituents of Ocimum gratissimum extract

“…PA increased the total apoptotic dead percentage from 19.40 % at 10 μM concentration to 72.40 % at 20 μM while TA risen from 27.56 % to 29.11 % at the same concentrations. This result is consistent with the literature since the apoptosis-inducing effect of PA and TA was previously reported in glioblastoma cells (Guimaraes et al, 2017) and vascular smooth muscle cells (Fogo et al, 2003).…”

Pomolic acid exhibits anticancer potential against a docetaxel‑resistant PC3 prostate cell line

“…The antitumor activity of triterpenes in several cancer lineages, including PC, is well known (13,15,21,33,34). Similar to other triterpenes, PA shows potent antitumor activity, reducing the viability and inducing apoptosis of different tumor cell lines (17,35,36) including cancer cells presenting different MDR mechanisms (18). Our results (Fig.…”

Recent Advances Regarding the Molecular Mechanisms of Triterpenic Acids: A Review (Part II)

“…Specifically, PA treatment increased caspase-3 and -9 activity and ROS production while decreasing the mitochondrial transmembrane potential in a time-dependent manner; the results indicate that the PA pro-apoptotic mechanism of action involves the activation of the intrinsic pathway in the presence of increased ROS production. The inhibition of glioblastoma cell migration in the same study was revealed to be a consequence of PA’s ability to down-modulate the activity of MRP1/ABCC1, two important transporter proteins involved in tumor drug resistance and progression [ 224 ]. Martins et al investigated the molecular mechanisms behind the antitumor activity of PA in parental PC3 and docetaxel-resistant prostate cancer PC3R cell lines and revealed a decrease in cell viability accompanied by cell apoptosis.…”