Antiproliferative activity of Cinnamomum cassia constituents and effects of pifithrin-alpha on their apoptotic signaling pathways in Hep G2 cells
Journal
Evidence-based Complementary and Alternative Medicine
Journal Volume
2011
Journal Volume
2011
Start Page
492148
ISSN
17414288
Date Issued
2011
Author(s)
Wu, Shu-Jing
Abstract
Cinnamaldehyde (Cin), cinnamic acid (Ca) and cinnamyl alcohol (Cal), major constituents of Cinnamomum cassia, have been shown to possess antioxidant, anti-inflammatory, anticancer and other activities. In this study, our aim was to evaluate the antiproliferative activity of these compounds in human hepatoma Hep G2 cells and examine the effects of pifithrin-alpha (PFT; a specific p53 inhibitor) on their apoptotic signaling transduction mechanism. The antiproliferative activity was measured by XTT assay. Expression of apoptosis-related proteins was detected by western blotting. Results showed that at a concentration of 30M, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC50 9.76 ± 0.67μM) demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC50 9.57 ± 0.61μM). Further studies on apoptotic mechanisms of Cin showed that it downregulated the expression of Bcl-XL, upregulated CD95 (APO-1), p53 and Bax proteins, as well as cleaving the poly (ADP-ribose) polymerase (PARP) in a time-dependent pattern. PFT pre-incubation significantly diminished the effect of Cin-induced apoptosis. It markedly upregulated the anti-apoptotic (Bcl-XL) expression and downregulated the pro-apoptotic (Bax) expression, as well as effectively blocking the CD95 (APO-1) and p53 expression, and PARP cleavage in Cin-treated cells. This study indicates that Cin was the most potent antiproliferative constituent of C. cassia, and its apoptotic mechanism in Hep G2 cells could be mediated through the p53 induction and CD95 (APO-1) signaling pathways.
SDGs
Other Subjects
cinnamaldehyde; cinnamic acid; Cinnamomum cassia extract; cinnamyl alcohol; Fas antigen; fluorouracil; nicotinamide adenine dinucleotide adenosine diphosphate ribosyltransferase; pifithrin alpha; protein Bax; protein bcl xl; protein p53; antineoplastic activity; antiproliferative activity; apoptosis; article; cell assay; cell proliferation; cell strain HepG2; Cinnamomum cassia; concentration response; controlled study; down regulation; drug effect; drug potency; drug screening; human; human cell; IC 50; liver cell carcinoma; priority journal; protein analysis; protein cleavage; protein induction; signal transduction; upregulation; Western blotting
Type
journal article