Garcinol exhibits anti-proliferative activities by targeting microsomal prostaglandin E synthase-1 in human colon cancer cells

Abstract

<jats:sec><jats:title>Background:</jats:title><jats:p> Colorectal cancer is the fourth leading cause of death. Various natural compounds are known to have antitumor properties. Garcinol, a polyisoprenylated benzophenone, has antioxidant and anti-inflammatory properties. In the current study, we investigated the anticancer activity of garcinol on human colorectal adenocarcinoma cell line (HT-29) human colon cancer cells. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> HT-29 cells were treated with various concentrations of garcinol for 24 h. The effect of garcinol on HT-29 cells proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; the mRNA expression of microsomal prostaglandin E synthase-1 (mPGES-1), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), C-X-C chemokine receptor type 4 (CXCR4), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9) were examined by quantitative real-time polymerase chain reaction; apoptosis was detected by proportion of sub-G1 cell; caspase 3 activity and prostaglandin E2 (PGE2) level were determined by enzyme-linked immunosorbent assay and HT-29 cells migration was assessed using scratch test. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Garcinol preconditioning markedly decreased the expression of mPGES-1, HIF-1α, VEGF, CXCR4, MMP-2, and MMP-9. The proportion of cells in sub-G1 phase and caspase 3 activity were increased by garcinol treatment whereas the cell proliferation, PGE2 level, and cell migration were decreased in these cells, compared to the control group. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Our findings suggest that garcinol plays a critical role in elevating apoptosis and inhibiting HT-29 cells proliferation, angiogenesis, and invasion by suppressing the mPGES-1/PGE2/HIF-1α signaling pathways. </jats:p></jats:sec>

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

“…Increased apoptosis and cell growth inhibition (garcinol), inhibition of angiogenesis and invasion (garcinol), inhibition of DNA repair (garcinol)…”

“…Suppression of mPGES1, HIF‐1 α , VEGF, MMP (garcinol), inhibition of base excision repair via HAT inhibition (garcinol)…”

“…25 % of CRC appears in people with close relatives suffering from CRC), as well as obesity and dietary factors . HT‐29 CRC cells treated with garcinol showed increased apoptosis rates, reduced cell growth, and a less pronounced tendency to angiogenesis and invasion due to downregulation of mPGES1, HIF‐1 α , VEGF and MMP expression . In HCT‐116 CRC cells, the HAT inhibitory activity of garcinol reduced 8‐oxoG damage repair by suppression of base excision repair (BER) …”

“…Increased apoptosis and cell growth inhibition (garcinol), [33] inhibition of angiogenesis and invasion (garcinol), [33] inhibition of DNA repair (garcinol) [34] Suppression of mPGES1, HIF-1α, VEGF, MMP (garcinol), [33] inhibition of base excision repair via HAT inhibition (garcinol) [34] -Breast cancer Sensitization to taxol (garcinol), [36] increased apoptosis (garcinol) [13] Suppression of caspase-3/iPLA 2 and NF-κB/Twist1 signaling (garcinol), [36] p53 dependent induction of Bax (garcinol), [13] suppression of Bcl-X L (garcinol), [13] proteasome-based degradation of ADA3 (garcinol) [55] Sensitization to taxol in orthotopic 4T1 mammary carcinoma (garcinol) [36] Prostate cancer…”

Sulforaphane, a Chemopreventive Compound, Inhibits Cyclooxygenase-2 and Microsomal Prostaglandin E Synthase-1 Expression in Human HT-29 Colon Cancer Cells

“…Increased levels of cyclooxygenase 2 (COX-2) expression are seen in 85% of patients with CRC [Chan et al, 2007;Saltz 2007;Wang and DuBois, 2010]. PGE2 signaling stimulates the proliferation, metastasis, angiogenesis, and chemoresistance of cancer cells and inhibits apoptosis [Buchanan et al, 2003;Kamiyama et al, 2006;Kaur and Sanyal, 2010;Kurtova et al, 2015;Ranjbarnejad et al, 2017b].…”