Cinnamic acid: A natural product with potential use in cancer intervention

Abstract

Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, has a long history of human exposure. We now show that cinnamic acid induces cytostasis and a reversal of malignant properties of human tumor cells in vitro. The concentration causing a 50% reduction of cell proliferation (IC50) ranged from 1 to 4.5 mM in glioblastoma, melanoma, prostate and lung carcinoma cells. Using melanoma cells as a model, we found that cinnamic acid induces cell differentiation as evidenced by morphological changes and increased melanin production. Moreover, treated cells had reduced invasive capacity associated with modulation of expression of genes implicated in tumor metastasis (collagenase type IV, and tissue inhibitor metalloproteinase 2) and immunogenicity (HLA-A3, class-I major histocompatibility antigen). Further molecular analysis indicated that the anti-tumor activity of cinnamic acid may be due in part to the inhibition of protein isoprenylation known to block mitogenic signal transduction. The results presented here identify cinnamic acid as a new member of the aromatic fatty acid class of differentiation-inducers with potential use in cancer intervention.

Problems of Reproducibility and Efficacy of Bioassays Using Crude Extracts, with reference to Aloe vera

“…[42,43] In contrast, cinnamic acid has been shown to down-regulate expression of cell proliferation and anti-apoptotic gene products, although the affects of both high and low concentrations were not examined. [100,101] The redox environment affects cellular signal transduction, DNA and RNA synthesis, protein synthesis, enzyme activation, regulation of the cell cycle, ligand binding, DNA binding and nuclear translocation, and therefore ultimately cell proliferation/ death. [102,103] Transcription factors are active in their reduced form and their translocation to the nucleus is also redox dependent.…”

Cytotoxicity of Coprinopsis atramentaria extract, organic acids and their synthesized methylated and glucuronate derivatives

“…Cinnamic acid was also pointed out as possessing antitumor activity against human malignant tumors, including melanoma, glioblastoma, adenocarcinoma of the prostate and lung (Liu, Hudgins, Shack, Yin, & Samid, 1995) and colon adenocarcinoma (Ekmekcioglu et al, 1998). Drupanin and baccharin, two cinnamic acid derivatives, were reported as inhibitors of the growth of HeLa-60 cell lines by inducing apoptosis (Akao et al, 2003).…”

Recycling antimalarial leads for cancer: Antiproliferative properties of N-cinnamoyl chloroquine analogues

“…cinnamic acids, which are found in different natural resources and widely used for diverse medicinal purposes, 3,4 have demonstrated to constitute scaffolds of great interest for the development of new antitumor agents. 5,6 In one hand, quinoline synthetic versatility promotes the development of large diversity of quinoline analogues.…”

“…2,8 In the case of cinnamic acid, it has been reported that one of its modes of action seems to be inhibition of protein isoprenylation, which blocks mitogenic signal transduction. 4 Still, cinnamic acid analogues have also shown to be antiangiogenic, antileukemic as well as inhibitors of transglutaminase, aminopeptidase N, DNA synthesis, and of a specific tyrosine kinase. 5,9 The introduction of a cinnamic acid moiety has also demonstrated to boost the antitumor activity of parent antitumor compounds; for instance, distamycin A, 2 in Figure 1, (IC 50 = 7.2 ng/mL) which includes a cinnamoyl functionality, showed antileukemic activity superior to that presented by tallimustine, 3 in Figure 1 (IC 50 = 50.3 ng/mL).…”