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Planta Med 2013; 79(03/04): 219-226
DOI: 10.1055/s-0032-1328130
Biological and Pharmacological Activity
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

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

Jaiprakash R. Patil
1   Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA
2   Department of Crop Physiology, University of Agricultural Sciences, Dharwad, India
,
Guddadarangavvanahally K. Jayaprakasha
1   Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA
,
Jinhee Kim
1   Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA
,
Kotamballi N. Chidambara Murthy
1   Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA
,
Mahadev B. Chetti
2   Department of Crop Physiology, University of Agricultural Sciences, Dharwad, India
,
Sang-Yong Nam
3   Natural Science Research Institute, Department of Horticulture, Sahmyook University, Seoul, Republic of Korea
,
Bhimanagouda S. Patil
1   Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA
› Author Affiliations
Further Information

Publication History

received 20 June 2012
revised 05 December 2012

accepted 11 December 2012

Publication Date:
23 January 2013 (online)

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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.

Key words

Citrus aurantifolia L. Osbeck - Rutaceae - coumarins - colon cancer - apoptosis - 5-geranyloxy-7-methoxycoumarin

Supporting Information

 

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