Apoptotic Effect of Caffeic Acid Phenethyl Ester and Its Ester and Amide Analogues in Human Cervical Cancer ME180 Cells

Mei Whey Hung, Ming Shi Shiao, Lai Chen Tsai, Gu Gang Chang, Tsu Chung Chang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

50 Scopus citations

Abstract

Background: Caffeic acid phenylether ester (CAPE) has potent antioxidant, anti-inflammatory, antiviral, anti-proliferative, immunomodulatory and pro-apoptotic activities. The activities of CAPE and its novel synthetic derivatives, caffeic acid octyl ester (CAO) and 1-octyl caffeamide (CAN-8), were investigated in this study. Materials and Methods: Cultured human cells were incubated with or without these compounds. The effect of these compounds on cell apoptosis, intracellular level of hydrogen peroxide and mitochondrial potential were analyzed. Western blot analysis was used to study the effect of alterations in protein level of caspases, Bcl-2 family, p21, p53 and c-Jun upon drug treatment. Results: These compounds arrested cell proliferation, triggered cell apoptosis and caused a marked scavenging effect of hydrogen peroxide. Apoptosis induced by CAPE or CAO is associated with increased expression of p53, p21 and c-Jun. While the levels of Bcl-2 and Bcl-xL were relatively unchanged, these compounds induced a marked reduction in Mcl-1 level. The CAPE- or CAO-induced apoptosis was also accompanied by a rapid loss of mitochondrial transmembrane potential and activation of caspase-3 and caspase-8, suggesting a mitochondrial-dependent mechanism. In causing these cellular actions, CAO was shown to be comparable or more potent than CAPE, whereas the amide analogue CAN-8 displayed much weaker activities than both CAPE and CAO. Since these three compounds contain similar antioxidant functionality, the difference in their potency suggests that the octyl moiety in CAO is an important determinant for the enhanced activities. Conclusion: We have characterized a novel CAPE structure analogue, CAO, which showed strong antioxidant and proapoptotic activities. In addition, we demonstrated that downregulation of Mcl-1 gene expression and activation of caspase-8 are associated with CAPE-triggered cell apoptosis.

Original languageEnglish
Pages (from-to)4773-4780
Number of pages8
JournalAnticancer Research
Volume23
Issue number6 C
StatePublished - 11 2003
Externally publishedYes

Keywords

  • Antioxidant
  • Apoptosis
  • CAPE
  • Caspase-8

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