Withaferin A, a cytotoxic steroid from Vassobia breviflora, induces apoptosis in human head and neck squamous cell carcinoma.
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% (IC(50)) were determined by the MTS cytotoxicity assay, and 1 reduced cell viability with IC(50) 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 G(0)/G(1) to G(2)/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.
Samadi
Abbas K
AK
Department of Surgery, School of Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.
Tong
Xiaoqin
X
Mukerji
Ridhwi
R
Zhang
Huaping
H
Timmermann
Barbara N
BN
Cohen
Mark S
MS
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001118:Argentina; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D002453:Cell Cycle / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D015394:Molecular Structure; D010946:Plants, Medicinal / Q000737:chemistry*; D019657:Solanaceae / Q000737:chemistry*; D054358:Withanolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*
D000972:Antineoplastic Agents, Phytogenic; D054358:Withanolides; C009684:withaferin A