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Cytotoxic Efficacy of Photodynamic Therapy in Osteosarcoma Cells In Vitro
Published on: March 18, 2014
Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism
Bilal Bin Hafeez1, Salahuddin Ahmed, Naizhen Wang
1Division of Rheumatic Diseases, Department of Medicine, Case Western Reserve University, 2109 Adelbert Road, BRB-319, Cleveland, OH 44106-4946, USA.
Abstract:
Development of chemotherapy resistance and evasion from apoptosis in osteosarcoma, a primary malignant bone tumor, is often correlated with constitutive nuclear factor-kappaB (NF-kappaB) activation. Here, we investigated the ability of a polyphenolic fraction of green tea (GTP) that has been shown to have antitumor effects on various malignant cell lines to inhibit growth and induce apoptosis in human osteosarcoma SAOS-2 cells. Treatment of SAOS-2 cells with GTP (20-60 microg/ml) resulted in reduced cell proliferation and induction of apoptosis, which correlated with decreased nuclear DNA binding of NF-kappaB/p65 and lowering of NF-kappaB/p65 and p50 levels in the cytoplasm and nucleus. GTP treatment of cells reduced IkappaB-alpha phosphorylation but had no effect on its protein expression. Furthermore, GTP treatment resulted in the inhibition of IKK-alpha and IKK-beta, the upstream kinases that phosphorylate IkappaB-alpha. The increase in apoptosis in SAOS-2 cells was accompanied with decrease in the protein expression of Bcl-2 and concomitant increase in the levels of Bax. GTP treatment of SAOS-2 cells also resulted in significant activation of caspases as was evident by increased levels of cleaved caspase-3 and caspase-8 in these cells. Treatment of SAOS-2 cells with a specific caspase-3 inhibitor Ac-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO) and general caspase inhibitor N-benzyloxycarbonyl-Val-Ala-Asp (OMe)-fluoromethyl ketone (Z-VAD-FMK) rescued SAOS-2 cells from GTP-induced apoptosis. Taken together, these results indicate that GTP is a candidate therapeutic for osteosarcoma that mediates its antiproliferative and apoptotic effects via activation of caspases and inhibition of NF-kappaB.
Insights
Green tea polyphenols (GTP) inhibit osteosarcoma growth by blocking nuclear factor-kappaB (NF-kappaB) activation and promoting apoptosis through caspase activation. This study highlights GTP as a potential therapeutic agent for bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma chemotherapy resistance is linked to nuclear factor-kappaB (NF-kappaB) activation.
- Green tea polyphenols (GTP) exhibit antitumor properties against various cancer cell lines.
Purpose of the Study:
- To investigate GTP's efficacy in inhibiting growth and inducing apoptosis in human osteosarcoma SAOS-2 cells.
- To elucidate the molecular mechanisms underlying GTP's effects, focusing on NF-kappaB signaling and apoptosis pathways.
Main Methods:
- SAOS-2 cells were treated with varying concentrations of GTP.
- NF-kappaB/p65 DNA binding, protein levels, IkappaB-alpha phosphorylation, and upstream kinases (IKK-alpha/beta) were assessed.
- Apoptosis-related proteins (Bcl-2, Bax), caspase activation (caspase-3, caspase-8), and the effects of caspase inhibitors were evaluated.
Main Results:
- GTP treatment significantly reduced SAOS-2 cell proliferation and induced apoptosis.
- GTP inhibited NF-kappaB activation by decreasing nuclear DNA binding and protein levels, and by reducing IkappaB-alpha phosphorylation and IKK-alpha/beta activity.
- GTP altered Bcl-2/Bax expression, activated caspases-3 and -8, and its pro-apoptotic effects were reversed by caspase inhibitors.
Conclusions:
- GTP demonstrates significant antiproliferative and pro-apoptotic effects on osteosarcoma cells.
- GTP's therapeutic potential in osteosarcoma is mediated by the inhibition of NF-kappaB signaling and the activation of caspase-dependent apoptosis.
- GTP represents a promising candidate for osteosarcoma therapy.
