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6-Shogaol Inhibits Breast Cancer Cells and Stem Cell-Like Spheroids by Modulation of Notch Signaling Pathway and Induction of Autophagic Cell Death

March 14, 2016 -

Ginger (Zingiber officinale) is a well known herb consumed as a spice and food as well as widely used as herbal medicine for various ailments. A number of biologically active ingredients including gingerols and its various derivatives have been identified and synthesized from ginger in recent years.

One important class of derivatives are shogaols that are primarily the dehydrated products of gingerols and are found exclusively in dried ginger. Among the shogaols, 6-shogaol has achieved a great deal of attention due to its potent anticancer activity against various cancer cells. It has been shown to induce mitotic arrest and reduce viability of gastric cancer cells. Aberrant mitosis followed by apoptosis has also been found to be induced by 6-shogaol in HCT-116 colon cancer cells.

In human hepatoma p53 mutant Mahlavu subline, 6-shogaol induces apoptosis via oxidative stress pathway in a caspase dependent mechanism. It has also been shown to induce autophagy in HNSCLC A-549 cells via inhibition of the AKT/mTOR pathway. In another study, 6-shogaol has been reported to exhibit anti-invasive effects in breast cancer cells by reducing MMP-9 expression through NF-κB activation. Recently, PPAR-γ dependent apoptosis in MCF-7 and HT-29 cells by 6-shogaol has also been reported.

Additionally, recent studies have implicated microtubule as a possible target of 6-shogaol as it interacts with the sulphydryl groups of cysteines in tubulin through its side chain containing the α, β unsaturated carbonyl moiety. All these studies place 6-shogaol as a promising agent to be studied further in view of its future therapeutic potential in cancer therapy.

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