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Cytotoxic and antineoplastic effects of citrus limonoids against human neuroblastoma and colonic adenocarcinoma cells
Author(s) -
Poulose Shibu M.,
Harris Edward D.,
Patil Bhimanagouda S.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a11-d
Subject(s) - limonin , limonoid , apoptosis , chemistry , glycoside , cell culture , chinese hamster ovary cell , cell cycle , cell cycle checkpoint , programmed cell death , viability assay , cell , microbiology and biotechnology , biochemistry , biology , stereochemistry , genetics , receptor
Limonoids, a class of naturally occurring triterpenoids, are unique in citrus among the edible fruits. Specific limonoid glucosides and aglycones, isolated in pure form were tested for their anticancer effects against two human cancer cell lines, SH‐SY5Y neuroblastoma and Caco‐2 colon carcinoma, and the non‐cancerous Chinese hamster ovary (CHO) cells. Cells were exposed to 1–50 μ M, aglycones and glucosides of limonin, nomilin, obacunone and deacetylnomilin for about 48 h. Viability of the cancer cells was shortened significantly ( P <0.001) at concentrations as low as 5 μ M for 24–48 h. The compounds showed little if any change in live cells or cell morphology of non‐cancerous CHO cells. Glucosides sharply reduced the cell viability as compared to aglycones ( P <0.005). By 36 h aglycones achieved only about half the killing rate of glycosides, which is preempted by a rise in caspase 3/7 activity, providing clear evidence for apoptosis in the death mechanism. Glucosides of limonin and obacunone arrested cell cycle, induced aneuploidy and promoted a rapid destruction of DNA within 36 h. Flow cytometric analysis of SH‐SY5Y cells showed that glucosides and aglycones caused a marked increase in aneuploidic cells, which is consistent with an arrest of the cell cycle at the G2/M phase. The results suggest that both limonoid aglycones and glycosides induce cell arrest but glucosides are the active apoptosis‐inducing factor in situ. Supported by USDA 2001‐52102‐11257, USDA 2004‐34402‐14768.