The Chloroform Fraction of Lemon (Citrus Limon) Leaves Inhibits Human Gastric Cancer Cell Proliferation via Induction of Apoptosis

Abstract

Little information about the biological activities of Citrus limon (lemon) leaves has been reported, whereas the fruit of Citrus limon (lemon) has been well-documented to contain various pro-health bio-functional compounds. In the present study, the antiproliferative activities of the lemon leaves were evaluated using several cancer cell lines. From the n-hexane, chloroform, ethyl acetate, n-butanol, and water fractions of methanolic extract of the leaves, the chloroform fraction of lemon leaves (CFLL) showed the most potent antiproliferative activity in the AGS human gastric cancer cells. The current study demonstrates that CFLL induces apoptosis in AGS cells, as evidenced by an increase in apoptotic bodies, cell population in the sub-G1 phase, Bax/Bcl-2 ratio, and cleavage of poly (ADP-ribose) polymerase (PARP), caspase-3 and caspase-9. Compositional analysis of the CFLL using gas chromatography mass spectrometry (GC-MS) resulted in the identification of 27 compounds including trans,trans-farnesol (3.19%), farnesol (3.26%), vanillic acid (1.45%), (-)-loliolide (5.24%) and palmitic acid (6.96%). Understanding the modes of action of these compounds individually and/or synergistically would provide useful information about their applications in cancer prevention and therapy.