Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism with downregulation of nuclear factor-κB

Bilal Hafeez, Salahuddin Ahmed, Naizhen Wang, Sanjay Gupta, Ailin Zhang, Tariq M. Haqqi

Research output: Contribution to journalArticle

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Abstract

Development of chemotherapy resistance and evasion from apoptosis in osteosarcoma, a primary malignant bone tumor, is often correlated with constitutive nuclear factor-κB (NF-κB) 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 μg/ml) resulted in reduced cell proliferation and induction of apoptosis, which correlated with decreased nuclear DNA binding of NF-κB/p65 and lowering of NF-κB/p65 and p50 levels in the cytoplasm and nucleus. GTP treatment of cells reduced IκB-α phosphorylation but had no effect on its protein expression. Furthermore, GTP treatment resulted in the inhibition of IKK-α and IKK-β, the upstream kinases that phosphorylate IκB-α. 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-κB.

Original languageEnglish (US)
Pages (from-to)11-19
Number of pages9
JournalToxicology and Applied Pharmacology
Volume216
Issue number1
DOIs
StatePublished - Oct 1 2006

Fingerprint

Polyphenols
Tea
Osteosarcoma
Caspases
Guanosine Triphosphate
Down-Regulation
Apoptosis
Chemical activation
Caspase Inhibitors
Caspase 3
Cells
Therapeutics
Phosphorylation
Chemotherapy
Caspase 8
Cell proliferation
Ketones
Tumors
Bone
Proteins

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

Green tea polyphenols-induced apoptosis in human osteosarcoma SAOS-2 cells involves a caspase-dependent mechanism with downregulation of nuclear factor-κB. / Hafeez, Bilal; Ahmed, Salahuddin; Wang, Naizhen; Gupta, Sanjay; Zhang, Ailin; Haqqi, Tariq M.

In: Toxicology and Applied Pharmacology, Vol. 216, No. 1, 01.10.2006, p. 11-19.

Research output: Contribution to journalArticle

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