Induction of apoptosis in human cervical carcinoma HeLa cells by polymethoxylated flavone-rich Citrus grandis Osbeck (Dangyuja) leaf extract.
Citrus grandis Osbeck (Dangyuja) has a high content of flavonoids with health-related properties. Although previous data have revealed the anticancer potency of some Citrus species, the underlying molecular mechanisms of this activity by leaf extracts have not been studied in detail. The purpose of this study was to evaluate the cytotoxic effects of citrus leaves on five human cancer cell lines and to determine the possible mechanisms of cell death elicited by the chloroform fraction (CF) of the Dangyuja leaf. The CF of Dangyuja strongly decreased the survival rate of HeLa cells, among the tested cell lines. CF treatment induced the down-regulation of anti-apoptotic Bcl-2 expression, resulting in the proteolytic activation of caspases and the degradation of poly (ADP-ribose) polymerase (PARP) protein. Arrested cell growth and induction of apoptosis were confirmed by flow cytometry and DNA fragmentation analysis, respectively. The major components of the CF were identified as isosinensetin, sinensetin, tetramethyl-O-isoscutellarein, nobiletin, tangeretin, and 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS). Our results suggest that the CF of Dangyuja leaves is an excellent source of functional polymethoxylated flavones, which may help prevent cervical cancer and may potentially be a useful agent for the treatment of certain malignancies.
Faculty of Biotechnology, College of Applied Life Sciences, Jeju National University, Jeju 690-756, Republic of Korea.
Hana
H
Kim
Jeong Yong
JY
Moon
Ashik
A
Mosaddik
Somi Kim
SK
Cho
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D002957:Citrus / Q000737:chemistry*; D053938:DNA Fragmentation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D047309:Flavones / Q000737:chemistry* / Q000494:pharmacology*; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology; D018515:Plant Leaves / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013778:Tetrazolium Salts; D013844:Thiazoles
D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D047309:Flavones; D010936:Plant Extracts; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue