Background:
Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor
activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects
on glioma cells remain unknown.
Objective:
This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines.
Methods:
The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion
assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect
of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression
and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A,
CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite
sequencing PCR (BSP-PCR).
Results:
Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased
the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression
of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing
the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and
caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53.
Conclusions:
It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism
for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a
promising anticancer candidate for further investigation.
-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth