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Withaferin A, a Cytotoxic Steroid from Vassobia breWiflora, Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma
Samadi, Abbas K. Tong, Xiaoqin Mukerji, Ridhwi Zhang, Huaping Timmermann, Barbara N. Cohen, Mark S.
Samadi, Abbas K.
Tong, Xiaoqin
Mukerji, Ridhwi
Zhang, Huaping
Timmermann, Barbara N.
Cohen, Mark S.
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Abstract
As part of a program to discover drug leads from plant biodiversity, the present investigation was undertaken to explore the anticancer potential of compounds derived from selected Latin American plants. Bioassay-guided fractionation of a crude extract of the aerial parts of Vassobia breviflora led to the isolation of the withanolide-type steroidal lactone withaferin A (1). This compound was tested for antiproliferative activity against the head and neck squamous cell carcinoma (HNSCC) cell lines, MDA1986, JMAR, UM-SCC-2, and JHU011. The inhibitory concentrations to reduce cell viability to 50% (IC50) were determined by the MTS cytotoxicity assay, and 1 reduced cell viability with IC50 values in the range 0.5−2.2 μM. A mechanistic study showed that 1 induces apoptosis and cell death in HNSCC cells as well as a cell-cycle shift from G0/G1 to G2/M. Cells treated with 1 exhibited inactivation of Akt and a reduction in total Akt concentration. This investigation constitutes the first report of the antiproliferative activity of withaferin A (1) against head and neck squamous carcinoma.
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2010-08-20
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Journal of Natural Products
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Samadi, Abbas K., Xiaoqin Tong, Ridhwi Mukerji, Huaping Zhang, Barbara N. Timmermann, and Mark S. Cohen. "Withaferin A, a Cytotoxic Steroid FromVassobia Breviflora, Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma." Journal of Natural Products 73.9 (2010): 1476-481.