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5-Acetyl-6,7,8,4-tetramethylnortangeretin induces apoptosis in multiplemyeloma U266 cells

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Multiple myeloma (MM) is one of the most common hematological malignancies and to date, it remains an incurable disease. In this study,we evaluated the inhibitory effect of 5-acetyloxy-6,7,8,4-tetramethoxyflavone (5-ATMF), a compound from aged citrus peel extracts, on theMM U266 cell line. We found that the compound inhibited cell growth and induced cell apoptosis in multiple apoptotic assays. The apoptoticproteins caspase-3, caspase-9, and PARP (poly ADP-ribose polymerase) were cleaved when cells were treated with 5-ATMF. Along with theapoptosis process, the anti-apoptotic protein, Bcl-2 (B-cell lymphoma-2), was significantly downregulated and the pro-apoptotic protein, Bax(Bcl-2 associated X protein), upregulated along with the release of cytochrome C (Cyt c) and the reduction of mitochondrial membrane potential(MMP). Notably, we found that the phosphorylation of Bad (Bcl-2/Bcl-XL-associated death promoter) was decreased but Bad remained unchangedin this process. On adding 5-ATMF to U266 cells, we observed that 5-ATMF repressed the phosphorylation of Akt (PKB Protein Kinase B PKB),thereby increasing the release of Cyt c and inhibiting the phosphorylation of Bad. These effects were enhanced by Ly294002, an inhibitor of Akt.These results suggested that 5-ATMF exerts a pro-apoptotic effect on U266 cells, possibly associated with the mitochondrial apoptotic pathwayinduced by the PI3K/Akt/Bad pathway.

Keywords: Citrus peel extract; Polymethoxylated flavones; 5-Acetyl-6,7,8,4-tetramethylnortangeretin; Multiple myeloma; Apoptosis

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Informasi Detail

Judul Seri

Food Science and Human Wellness

No. Panggil

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Penerbit

: Elsevier B.V.., 2014

Deskripsi Fisik

Food Science and Human Wellness 3 (2014) 197–203

Bahasa

English

ISBN/ISSN

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Klasifikasi

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Tipe Isi

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Tipe Media

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Tipe Pembawa

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Edisi

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Subjek

Food And Health

Info Detail Spesifik

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Pernyataan Tanggungjawab

Wati/Agus

Versi lain/terkait

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