PT93, a novel caffeic acid amide derivative, suppresses glioblastoma cells migration, proliferation and MMP-2/−9 expression

Abstract

Abstract. Glioblastoma multiforme (GBM) is the most malignant type of primary brain tumor in adults and can diffusely infiltrate adjacent normal tissue. GBM is therefore rarely cured by surgery or radiation therapy. Matrix metalloproteinases (MMPs) are involved in tissue remodeling and numerous other physiological progresses. The MMPs MMP-2 and MMP-9 are associated with the invasion ability of GBM. PT93 is a novel caffeic acid amide derivative that was first synthesized in 2013. In the present study, the human GBM T98G, U87 and U251 cell lines and the normal mouse neuron HT22 cell line were used to investigate the anticancer and cytotoxic effects of PT93 in vitro. The cytotoxicity of PT93 was measured using MTT and lactate dehydrogenase assays. The anti-proliferation effect was tested using a cell colony formation assay. Gelatin zymography analysis and a scratch test were used to investigate the anti-migration mechanism of PT93. Western blot analysis was used to measure the expression of MMP-2/-9. The experimental results showed that PT93 suppressed the proliferation of T98G cells, and showed cytotoxicity effects at high concentration in T98G, U87, U251 and HT22 cell lines. Furthermore, PT93 limited the migration ability of the cells and inhibited the extracellular MMP-2 and MMP-9 activity of T98G and U251 cells. Finally, the present study confirmed that PT93 affects the level of MMP-2/-9 expression in T98G cells in a concentration-dependent manner. The present study indicates that PT93, as a novel caffeic acid amide derivative, may be used in the treatment of GBM.

Silencing microRNA‐221/222 cluster suppresses glioblastoma angiogenesis by suppressor of cytokine signaling‐3‐dependent JAK/STAT pathway

“…Moreover, MMP‐9 and MMP‐2 are two overexpressed MMPs measured in gliomas and the loss of activity of MMP‐9 induced by MMP‐9 hemopexin‐like domain (PEX) exerts inhibitory effects on glioblastoma angiogenesis and intracranial growth of xenograft in nude mice (Ezhilarasan et al, ). The invasive capacity of glioblastoma cells is suggested to be linked to MMP‐9 and MMP‐2, and PT93 could suppress the migration of glioblastoma cells through inhibiting the activities of MMP‐9 and MMP‐2 (K. Li et al, ). miR‐21, a critical miRNA which is highly expressed in glioblastoma cells and links to glioblastoma angiogenesis (Hermansen, Nielsen, Aaberg‐Jessen, & Kristensen, ), was previously suggested to promote angiogenesis in HUVECs via regulation of MMP‐9 and MMP‐2 expressions (Hu et al, ).…”

The Inhibitory Effects of Terminalia catappa L. Extract on the Migration and Invasion of Human Glioblastoma Multiforme Cells

“…Jiang et al revealed that tetrandrine, which is isolated from the root of Stephania tetrandra S. Moore, inhibits GBM8401 cancer cell migration and invasion in vitro [59]. A novel caffeic acid amide derivative, PT93, suppresses MMP-2 and MMP-9 expression in human GBM cell lines [55]. Our results reveal that TCE inhibits the migration abilities of GBM cells by suppressing MMP-2 expression.…”

“…It has also been shown to play a key role in the invasion and metastasis of different types of human cancer cells [50][51][52][53][54]. A few studies have found high expression of MMP-2 has in high-grade astrocytic tumors in comparison to normal brain tissue [55,56]. In addition, the expression levels of MMP-2 were significantly elevated in TMZ-resistant GBM cells in comparison to parental GBM cells [57].…”

Dietary Polyphenols Effects on Focal Adhesion Plaques and Metalloproteinases in Cancer Invasiveness

“…Another caffeic acid ester, CADPE, was studied by Han et al, who demonstrated that it is able to reduce the invasive capacity of human gastric carcinoma and breast carcinoma cells by inhibiting the PMA-dependent MMP-9 activation pathway [205]. A similar inhibition of MMP-2 and MMP-9 activities was found upon treatment with a caffeic acid derivative, PT93 (>30 µM), on immortalized rat HSC-T6 cells [240]. Liu et al instead focused their studies on another compound belonging to the class of phenolic acids (GA) and demonstrated that GA treatment inhibited MMPs' activity in prostate carcinoma cells (PC-3) by increasing the synthesis of the inhibitor TIMP-1 [207].…”