Induction of apoptosis and reduction of MMP gene expression in the U373 cell line by polyphenolics in Aronia melanocarpa and by curcumin

Abstract

Malignant brain tumours are rare but are the most challenging types of cancers to treat. Despite conventional multimodality approaches available for their management, the outlook for most patients remains dismal due to the ability of the tumour cells to invade the normal brain. Attention has now focused on novel therapeutic interventions such as as the use of micronutrients. Both chokeberry extract (Aronia melanocarpa), which is rich in natural pigments such as anthocyanins and curcumin (diferuloylmethane) found in turmeric (Curcuma longa) have been reported to possess anticancer properties in other cancers. The aim of this study was to extend our previous research to evaluate the therapeutic potential of these two agents by testing their ability to induce apoptosis in an established glioblastoma cell line (U373). This was accomplished by treating the cells for 48 h with either chokeberry extract or curcumin, and using the Annexin-V assay. Gene profiles of 8 MMPs (2, 9, 14, 15, 16, 17, 24 and 25) and 4 TIMPs (1, 2, 3 and 4) were analysed for effects of mediators of invasion by quantitative real-time polymerase chain reaction (RT-PCR). The IC50 values determined for curcumin and chokeberry extract were 15 and 200 µg/ml, respectively. Our results also suggest that curcumin induces apoptosis but chokeberry extract is necrotic to this cell line. It is possible that chokeberry extract kills the cells by other non-apoptotic pathways. In addition, the RT-PCR results show downregulation of the gene expression of MMP-2, -14, -16 and -17 for both micronutrients. Taken together, the comparative data suggest that both curcumin and chokeberry extract may exhibit their anticancer potential by inducing apoptosis and inhibiting invasion by reducing MMP gene expression.

Drug target identification at the crossroad of neuronal apoptosis and survival

“…Although they are emerging as regulators of nervous system development and adult brain functions, their role in cell death remains to be elucidated [40,41]. Our in vitro data, however, show an increased expression of Mmp16 and Adam1a and the decrease of Adamts2 during CGNs rescue [15].…”

Therapeutic Potential of Curcumin for the Treatment of Brain Tumors

“…Data has shown that curcumin is able to suppress expression of MMP-1, MMP-3, MMP-9, and MMP-14 in GBM cell lines U87MG and U373MG via the common upstream AP-1 and MAP kinases [22, 23, 54]. Urokinase-type plasminogen activator (uPA) is a serine protease that starts a degradative cascade by converting extracellular plasminogen to plasmin and eventually degrades extracellular matrix collagen and activates other MMPs to aid in invasion [55].…”

High levels of apoptosis are induced in human glioma cell lines by co-administration of peptide nucleic acids targeting miR-221 and miR-222

“…Glioma cell lines and culture conditions. U251, U373 and T98G cells (39)(40)(41) were cultured in humidified atmosphere of 5% CO 2 /air in RPMI-1640 medium (Life Technologies, Monza, Italy) supplemented with 10% fetal bovine serum (FBS, Celbio, Milan, Italy), 100 U/ml penicillin and 100 mg/ml streptomycin. To verify the effect on proliferation, cell growth was monitored by determining the cell number/ml using a Z2 Coulter Counter (Coulter Electronics, Hialeah, FL, USA).…”