Activation of caspase-3 protease during the process of ursolic acid and its derivative-induced apoptosis

Ferenc Hollósy, Miklós Idei, Gézáné Csorba, Edit Szabó, Gyöngyi Bökönyi, Attila Seprödi, György Mészáros, Béla Szende, György Kéri

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35 Citations (Scopus)

Abstract

The apoptosis-inducing effect of the triterpene saponins, namely, ursolic acid and its natural derivative, methyl-ursolate β-D-glucoside on A431 human epidermoid carcinoma cells was studied. The cells treated with 5-50 μg/ml of ursolic acid resulted in a dose-and time-dependent decrease in cell number, due to an increase of apoptotic cells as evidenced by MTT assay together with morphological changes. The highest dose (50 μg/ml) of ursolic acid resulted in approximately 90 % inhibition in tumor cell growth after 96 hours of treatment and 60 % of apoptosis after 48 hours. To the contrary, when the same treatment was carried out with methyl-ursolate β-D-glucoside, after 96 hours of treatment the percentage of cell growth inhibition was found to be only 30 % at the dose of 50 μg/ml and the value of apoptosis did not exceed 10 %. Similarly to these results, ursolic acid effectively induced proteolytic activation of caspase-3 protease in a dose-dependent manner while its derivative showed only weak activity in this enzyme assay. The addition of DEVD-CHO prior to ursolic acid and methyl-ursolate β-D-glucoside treatment effectively prevented the loss of triterpenes-induced viability. In summary, the triterpene saponins investigated contain an apoptotic-inducing activity in A431 cells and in the case of ursolic acid it is associated with proteolytic activation of caspase-3 and/or other similar caspases. Our results also indicated that methylation of COOH-28 together with the glycosylation of C3 of ursolic acid have a strong impact on its antitumor activity.

Original languageEnglish
Pages (from-to)3485-3491
Number of pages7
JournalAnticancer research
Volume21
Issue number5
Publication statusPublished - Dec 1 2001

Keywords

  • A431 human epidermoid carcinoma cell
  • Apoptosis
  • Caspase-3 protease
  • Methyl-ursolate β-D-glucoside
  • Ursolic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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