5-Geranyloxy-7-Methoxycoumarin Inhibits Colon Cancer (SW480) Cells Growth by Inducing Apoptosis

Abstract

For the first time, three coumarins were isolated from the hexane extract of limes (Citrus aurantifolia) and purified by flash chromatography. The structures were identified by NMR (1D, 2D) and mass spectral analyses as 5-geranyloxy-7-methoxycoumarin, limettin, and isopimpinellin. These compounds inhibited human colon cancer (SW-480) cell proliferation, with 5-geranyloxy-7-methoxycoumarin showing the highest inhibition activity (67 %) at 25 µM. Suppression of SW480 cell proliferation by 5-geranyloxy-7-methoxycoumarin was associated with induction of apoptosis, as evidenced by annexin V staining and DNA fragmentation. In addition, 5-geranyloxy-7-methoxycoumarin arrested cells at the G0/G1 phase, and induction of apoptosis was demonstrated through the activation of tumour suppressor gene p53, caspase8/3, regulation of Bcl2, and inhibition of p38 MAPK phosphorylation. These findings suggest that 5-geranyloxy-7-methoxycoumarin has potential as a cancer preventive agent.

Coumarins and a Triterpenoid from Pithecellobium dulce

“…The 1 H and 13 C NMR data and literature [15] show that the isolated compound 2 is 4(2,3-dihydrogeranyloxy)-5(4(2,3-dihydrogeranyloxy)phenylbergapten. [16].…”

Citrus Fruits and their Bioactive Ingredients: Leading Four Horsemen from Front

“…Another important link explored in the study was Ca2+-sensitive PKC exerted inhibitory effects on ERK induced signalling in Nobiletin treated cells (Aoki et al, 2013). Phosphorylated levels of p38 MAPK were also reduced in 5-Geranyloxy-7-methoxycoumarin treated colon cancer (SW480) cells (Patil et al, 2013).…”

“…5-Geranyloxy-7-methoxycoumarin, isolated from hexane extract of Citrus aurantifolia induced cell cycle arrest at G0/G1 phase in colon cancer (SW480) cells (Patil et al, 2013). Cell cycle arrest was induced in A549 lung cancer cells upon treatment with flavonoids isolated from Korean Citrus aurantium L (Park et al, 2012).…”

An insight into the role of citrus bioactives in modulation of colon cancer

“…In another study conducted by Patil et al (2013), the role of coumarins (5-geranyloxy-7-methoxycoumarin, limettin and isopimpinellin) present in Citrus aurantifolia was examined for their antiproliferative actions. In vitro studies on human colon cancer cells (SW480) showed that 5-geranyloxy-7-methoxycoumarin exhibited 67% growth inhibition at a dose of 25 µM.…”