5-Geranyloxy-7-methoxycoumarin inhibits colon cancer (SW480) cells growth by inducing apoptosis.
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.
Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, TX 77843, USA. b-patil@tamu.edu
Jaiprakash R
JR
Patil
Guddadarangavvanahally K
GK
Jayaprakasha
Jinhee
J
Kim
Kotamballi N Chidambara
KN
Murthy
Mahadev B
MB
Chetti
Sang-Yong
SY
Nam
Bhimanagouda S
BS
Patil
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D032082:Citrus aurantiifolia / Q000737:chemistry; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003374:Coumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D011564:Furocoumarins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
C442483:5-geranyloxy-7-methoxycoumarin; D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D011564:Furocoumarins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; C015304:isopimpinellin; D048051:p38 Mitogen-Activated Protein Kinases; C037446:5,7-dimethoxycoumarin