Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer

Laura Wright, Jen B. Frye, Bhavana Gorti, Barbara N. Timmermann, Janet L. Funk

Research output: Contribution to journalArticle

26 Citations (Scopus)

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 structurallyrelated 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 did not have any 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.

Original languageEnglish (US)
Pages (from-to)6218-6225
Number of pages8
JournalCurrent Pharmaceutical Design
Volume19
Issue number34
DOIs
StatePublished - 2013
Externally publishedYes

Fingerprint

Curcuma
Parathyroid Hormone-Related Protein
Inhibitory Concentration 50
Breast Neoplasms
ferulic acid
Curcumin
Complex Mixtures
Growth Hormone
Growth
Bone Neoplasms
Neoplasms
Volatile Oils
Neoplasm Metastasis
turmeric extract

Keywords

  • Breast
  • Cancer
  • Curcumin
  • Curcuminoid
  • Ferulic acid
  • Ginger
  • PTHrP
  • Tetrahydrocurcuminoids

ASJC Scopus subject areas

  • Drug Discovery
  • Pharmacology

Cite this

Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer. / Wright, Laura; Frye, Jen B.; Gorti, Bhavana; Timmermann, Barbara N.; Funk, Janet L.

In: Current Pharmaceutical Design, Vol. 19, No. 34, 2013, p. 6218-6225.

Research output: Contribution to journalArticle

Wright, Laura ; Frye, Jen B. ; Gorti, Bhavana ; Timmermann, Barbara N. ; Funk, Janet L. / Bioactivity of turmeric-derived curcuminoids and related metabolites in breast cancer. In: Current Pharmaceutical Design. 2013 ; Vol. 19, No. 34. pp. 6218-6225.
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