Aloe-emodin modulates PKC isozymes, inhibits proliferation, and induces apoptosis in U-373MG glioma cells.
Aloe-emodin (1,8-dihydroy-3-[hydroxymethyl]-anthraquione) purified from Aloe vera leaves has been reported to have antitumor activity. The objectives of our research were to determine how aloe-emodin regulates the cell cycle, cell proliferation and protein kinase C (PKC) during glioma growth and development. To establish the cell cycle effects of aloe-emodin on brain cells [transformed glia cell line (SVG) and human glioma U-373MG cell line (U-373MG)], cells were treated with either dimethylsulfoxide (DMSO; control) or aloe-emodin (40 microM). Results from flow cytometry demonstrated that aloe-emodin delayed the number of cells entering and exiting DNA synthesis (S) phase in both SVG and U-373MG cells indicating that aloe-emodin may inhibit S phase progression. Assessment of cell viability demonstrated that SVG and U-373MG glioma cell were highly sensitive to aloe-emodin. The aloe-emodin-induced decreased proliferation was sustained at 48-96 h. A PKC activity assay was quantified to establish the role of PKC in aloe-emodin's mode of action. Exposure of SVG and U-373MG glioma cells to aloe-emodin suppressed PKC activity and reduced the protein content of most of the PKC isozymes. We determined that cancer growth inhibition by aloe-emodin was due to apoptosis (i.e., programmed cell death). Taken together, these results support the hypothesis that aloe-emodin represents a novel antitumor chemotherapeutic drug.
Acevedo-Duncan
Mildred
M
Department of Chemistry, University of South Florida, Tampa, FL, USA. macevedo@chuma.cas.usf.edu
Russell
Christopher
C
Patel
Sapna
S
Patel
Rekha
R
D000880:Anthraquinones; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002458:Cell Fractionation; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D004642:Emodin / Q000494:pharmacology*; D005910:Glioma / Q000473:pathology*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects
D000880:Anthraquinones; D007527:Isoenzymes; D004247:DNA; C518327:aloe emodin; D011493:Protein Kinase C; D004642:Emodin