Withaferin A, a Cytotoxic Steroid from Vassobia breWiflora, Induces Apoptosis in Human Head and Neck Squamous Cell Carcinoma

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Issue Date
2010-08-20Author
Samadi, Abbas K.
Tong, Xiaoqin
Mukerji, Ridhwi
Zhang, Huaping
Timmermann, Barbara N.
Cohen, Mark S.
Publisher
Journal of Natural Products
Type
Article
Article Version
Scholarly/refereed, publisher version
Rights
Copyright © 2010 The American Chemical Society and American Society of Pharmacognosy
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Show full item recordAbstract
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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Citation
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.
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