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Bioactivity of Turmeric-Derived Curcuminoids and Related Metabolites in Breast Cancer
Wright, Laura E. Frye, Jennifer B. Gorti, Bhavana Timmermann, Barbara N. Funk, Janet L.
Wright, Laura E.
Frye, Jennifer B.
Gorti, Bhavana
Timmermann, Barbara N.
Funk, Janet L.
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Abstract
While the chemotherapeutic effect of curcumin, one of three major curcuminoids derived from turmeric, has been reported, largely unexplored are the effects of complex turmeric extracts more analogous to traditional medicinal preparations, as well as the relative importance of the three curcuminoids and their metabolites as anti-cancer agents. These studies document the pharmacodynamic effects of chemically-complex turmeric extracts relative to curcuminoids on human breast cancer cell growth and tumor cell secretion of parathyroid hormone-related protein (PTHrP), an important driver of cancer bone metastasis. Finally, relative effects of structurally-related metabolites of curcuminoids were assessed on the same endpoints. We report that 3 curcuminoid-containing turmeric extracts differing with respect to the inclusion of additional naturally occurring chemicals (essential oils and/or polar compounds) were equipotent in inhibiting human breast cancer MDA-MB-231 cell growth (IC50=10–16μg/mL) and secretion of osteolytic PTHrP (IC50=2–3μg/mL) when concentrations were normalized to curcuminoid content. Moreover, these effects were curcuminoid-specific, as botanically-related gingerol containing extracts had no effect. While curcumin and bis-demethoxycurcumin were equipotent to each other and to the naturally occurring curcuminoid mixture (IC50=58 μM), demethoxycurcumin was without effect on cell growth. However, each of the individual curcuminoids inhibited PTHrP secretion (IC50=22–31μM) to the same degree as the curcuminoid mixture (IC50=16 μM). Degradative curcuminoid metabolites (vanillin and ferulic acid) did not inhibit cell growth or PTHrP, while reduced metabolites (tetrahydrocurcuminoids) had inhibitory effects on cell growth and PTHrP secretion but only at concentrations ≥10-fold higher than the curcuminoids. These studies emphasize the structural and biological importance of curcuminoids in the anti-breast cancer effects of turmeric and contradict recent assertions that certain of the curcuminoid metabolites studied here mediate these anti-cancer effects.
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Date
2014-01-07
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Bentham Science Publishers
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Keywords
Curcumin, Breast cancer, Curcuminoid, Ginger, PTHrP, Ferulic acid, Tetrahydrocurcuminoids
Citation
Wright, Laura, Jen Frye, Bhavana Gorti, Barbara Timmermann, and Janet Funk. "Bioactivity of Turmeric-derived Curcuminoids and Related Metabolites in Breast Cancer." Current Pharmaceutical Design 19.34 (2013): 6218-225.