Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells - PubMed (original) (raw)

Antiproliferative Activity of Cinnamomum cassia Constituents and Effects of Pifithrin-Alpha on Their Apoptotic Signaling Pathways in Hep G2 Cells

Lean-Teik Ng et al. Evid Based Complement Alternat Med. 2011.

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 (PFTα; 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 30 μM, the order of antiproliferative activity in Hep G2 cells was Cin > Ca > Cal. Cin (IC(50) 9.76 ± 0.67 μM) demonstrated an antiproliferative potency as good as 5-fluorouracil (an anti-cancer drug; IC(50) 9.57 ± 0.61 μM). 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. PFTα 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.

PubMed Disclaimer

Figures

Figure 1

Figure 1

IC50 values of antiproliferative activity of cinnamaldehyde, cinnamic acid and cinnamyl alcohol. The data shown are means ± SD of three independent experiments. Bars with different alphabetical letters were significantly different at P < .05.

Figure 2

Figure 2

Effects of apoptotic signal transduction factors (CD95, p53, Bax, Bcl-XL and PARP) in Cin-induced cell death. Cells were treated with 30 _μ_M Cin for 0, 6, 12 and 24 h and then harvested for Western blotting analysis. _β_-Actin was used as a positive control.

Figure 3

Figure 3

Effects of the p53 inhibitor (PFT_α_) on Cin-induced cell death. The data represent means ± SD of three independent experiments. Bars with different alphabetical letters were significantly different at P < .05.

Figure 4

Figure 4

Effects of p53 inhibitor (PFT_α_) on Cin-induced apoptosis. Hep G2 cells were treated without or with 30 μ_M PFT_α for 1 h, and then in the presence or absence of 30 _μ_M Cin for 24 h. The total cell lysate was then analyzed by western blotting analysis. _β_-Actin was used as a positive control.

Figure 5

Figure 5

The mode of action of PFT_α_ on the Cin-mediated apoptosis in Hep G2 cells.

Similar articles

Cited by

References

    1. Lou ZQ, Qin B. Species Systematization and Quality Evaluation of Commonly Used Chinese Traditional Drugs. Vol. 1. Beijing, China: Beijing University Medical Press; 1995.
    1. Shijie Z, Moriya J, Yamakawa J, Chen R, Takahashi T, Sumino H. Mao-to prolongs the survival of and reduces TNF-α expression in mice with viral myocarditis. Evidence-Based Complementary and Alternative Medicine. 2008 - PMC - PubMed
    1. Chen FP, Jong MS, Chen YC, Kung YY, Chen TJ, Chen FJ. Prescriptions of Chinese herbal medicines for insomnia in Taiwan during 2002. Evidence-Based Complementary and Alternative Medicine. 2009 - PMC - PubMed
    1. Zhang LP, Ji ZZ. Synthesis, antiinflammatory and anticancer activity of cinnamic acids, their derivatives and analogues. Yao Xue Xue Bao. 1992;27:817–823. - PubMed
    1. Akao Y, Maruyama H, Matsumoto K, et al. Cell growth inhibitory effect of cinnamic acid derivatives from propolis on human tumor cell lines. Biological and Pharmaceutical Bulletin. 2003;26(7):1057–1059. - PubMed

LinkOut - more resources