Eurycomanone induces apoptosis through the upregulation of p53 in human cervical carcinoma (Hela) cells

Mahfudh, Nurkhasanah Eurycomanone induces apoptosis through the upregulation of p53 in human cervical carcinoma (Hela) cells. Journal of Cancer Molecules.

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AIM: Eurycomanone is a cytotoxic compound found in Eurycoma longifolia Jack.
Previous studies had noted the cytotoxic effect against various cancer cell lines. The
aim of this study is to investigate the cytotoxicity against human cervical carcinoma
cells and the mode of action.
METHODS: The cytotoxicity of eurycomanone was evaluated using methylene blue
staining assay and the mode of cell death was detected by Hoechst 33258 nuclear
staining, TUNEL assay and flow cytometry with Annexin-V/propidium iodide double
staining. The protein expression of p53, E6, E6-AP, Bax and Bcl-2 were studied by
Western blotting. Immunostaining assay was used to confirm the up-regulation of p53
and Bax in cancer cells.
RESULTS: The findings suggested that eurycomanone was cytotoxic on cancerous
cells (CaOv-3, HeLa, HepG2, HM3KO, MCF-7) and less toxic on normal cells (MDBK,
Vero). Furthermore, various methods proved that apoptosis was the mode of death in
eurycomanone-treated cervical cancer HeLa cells. The characteristics of apoptosis
including chromatin condensation, DNA fragmentation and apoptotic bodies were
found following eurycomanone treatment. This study also found that apoptotic process
triggered by eurycomanone involved the up-regulation of p53 tumor suppressor
protein. The up-regulation of p53 was followed by the increasing of pro-apoptotic Bax
and decreasing of anti-apoptotic Bcl-2. However, eurycomanone did not affect the E6
and E6-AP protein expression.
CONCLUSION: The data suggest that eurycomanone was cytotoxic on HeLa cells by
inducing apoptosis through the up-regulation of p53 and Bax, and down-regulation of
Bcl-2, independently of functional E6 and E6-AP activity.

Item Type: Artikel Umum
Subjects: R Medicine > RS Pharmacy and materia medica
Divisi / Prodi: Faculty of Pharmacy (Fakultas Farmasi) > S2-Master of Pharmacy (S2-Farmasi)
Depositing User: Dr Nurkhasanah Mahfudh
Date Deposited: 10 Jul 2012 03:00
Last Modified: 10 Jul 2012 03:00

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