Antiproliferative activities of Citrus aurantium against breast (MCF7), cervix (HeLa) and urinary bladder (EJ138) carcinoma cells

Citrus aurantium L. (Rutaceae), commonly known as bitter orange, is used in folklore medicine for the treatment of cancer, diabetes, malaria, painful swellings, typhoid and wounds [1]. In our search for cytotoxic agents from natural sources, we have recently carried out an ethnobotanical survey of plants used for cancer treatment amongst the Ijebu ethnic group of South-Western Nigeria, and C. aurantium has been frequently mentioned as a cancer remedy by several traditional healers.

The ground bark of this plant was Soxhlet-extracted, successively, with n-hexane, dichloromethane and methanol. As the dichloromethane extract showed significant cytotoxic activity (IC₅₀= 11.5 – 14.3 µg/mL) against the breast (MCF7), the cervix (HeLa) and the urinary bladder (EJ138) carcinoma cells in the MTT assay, it was subjected to Vacuum Liquid Chromatography (VLC) to obtain six (F1-F6) different fractions. Since F2-F3 displayed the highest activities amongst the fractions (IC₅₀= 8.55 – 10.38 µg/mL), the combined fractions were subjected to column chromatography and repeated preparative thin layer chromatography on silica gel leading to the isolation of an acridone alkaloid, citracidone-1. The structure of the alkaloid was elucidated by spectroscopic means. It could be assumed that citracidone-1, at least to a certain extent, accounts for the cytotoxic activity of C. aurantium, as its cytotoxic activity was documented in a previous study[2]. This study has demonstrated the cytotoxic property of C. aurantium and further investigations on citracidone-1 in relation to its anticancer potential and possible mechanism of action are underway.

[1] Arias BA, Ramón-Laca L. J. Ethnopharmacol. 2005; 97: 89 – 95

[2] Teng WY, Huang YL, Shen CC, Huang RL, Chung RS, Chen CC. J. Chin. Chem. Soc. 2005; 52: 1253 – 1255