Garcinia Benzophenones Inhibit the Growth of Human Colon Cancer Cells and Synergize with Sulindac Sulfide and Turmeric
Linda Saxe Einbond,
Ulyana Munoz Acuna,
David A. Foster,
Edward J. Kennelly.
Previous studies indicate that extracts and purified components from Garcinia species inhibit the growth of human colon
cancer cells. Garcinia benzophenones activate the expression of genes in the endoplasmic reticulum and cellular energy stress (mTOR)
pathways. This study examines the growth inhibitory and synergistic effects of Garcinia benzophenones, alone or combined with
chemopreventive agents, on human colon cancer cells. To find optimal combination treatments, HT29 colon cancer cells were treated
with benzophenones alone, or combined with chemopreventive agents, and cell growth measured using the MTT assay. To reveal effects
on signaling pathways, we assessed effects of the MEK inhibitor U0126 and the ER IP3 receptor antagonist heparin, as well as effects on
the phosphorylation of 4E-BP-1 (mTOR pathway), using Western blot analysis. New and known benzophenones from Garcinia
intermedia inhibited the growth of human colon cancer cells; an alcohol extract of Garcinia xanthochymus, as well as purified
guttiferones (guttiferone E and xanthochymol), preferentially inhibited the growth of colon cancer versus nonmalignant intestinal
epithelial cells. Guttiferone E exhibited synergy with the NSAID sulindac sulfide and xanthochymol, with the spice turmeric. Guttiferone
A did not alter phosphorylation of 4E-BP-1, indicating that the mTORC1 pathway is not involved in its action. The effects of
xanthochymol were enhanced by U0126, at low doses, and were blocked by heparin, indicating that the MEK pathway is involved, while
the ER IP3 receptor is critical for its action. These studies indicate the potential of benzophenones, alone or combined with sulindac
sulfide or turmeric, to prevent and treat colon cancer.
Keywords: Benzophenone, celecoxib, endoplasmic reticulum, Garcinia, rapamycin, sulindac sulfide, and turmeric, synergy.
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