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

Jaiprakash R. Patil; Guddadarangavvanahally K. Jayaprakasha; Jinhee Kim; Kotamballi N. Chidambara Murthy; Mahadev B. Chetti; Sang-Yong Nam; Bhimanagouda S. Patil

doi:10.1055/s-0032-1328130

Planta Medica, Table of Contents

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

¹Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA

²Department of Crop Physiology, University of Agricultural Sciences, Dharwad, India

,

Guddadarangavvanahally K. Jayaprakasha

¹Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA

,

Jinhee Kim

¹Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA

,

Kotamballi N. Chidambara Murthy

¹Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA

,

Mahadev B. Chetti

²Department of Crop Physiology, University of Agricultural Sciences, Dharwad, India

,

Sang-Yong Nam

³Natural Science Research Institute, Department of Horticulture, Sahmyook University, Seoul, Republic of Korea

,

Bhimanagouda S. Patil

¹Vegetable and Fruit Improvement Center, Department of Horticultural Sciences, Texas A&M University, College Station, Texas, USA

› Author Affiliations

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

Full Text

References

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