Regression of cervical intraepithelial neoplasia by zerumbone in female Balb/c mice prenatally exposed to diethylstilboestrol: Involvement of mitochondria-regulated apoptosis

被引：43

作者：

Abdelwahab, Siddig Ibrahim ^{[1
]}

Abdul, Ahmad Bustamam ^{[1
]}

Devi, Nirmala ^{[1
]}

Mohamed, Manal ^{[1
]}

Taha, Ehassan ^{[1
]}

Al-zubairi, Adel Sharaf ^{[1
]}

Mohan, Syam ^{[1
]}

Mariod, Abdelbasit Adam ^{[1
]}

机构：

[1] Univ Putra Malaysia, MAKNA UPM Canc Res Lab, Inst Biosci, Serdang 43400, Selangor, Malaysia

来源：

EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY | 2010年 / 62卷 / 05期

关键词：

Zerumbone; Cisplatin; Cervical intraepithelial neoplasia; Apoptosis; TUNEL assay; Bax protein; LASER CAPTURE MICRODISSECTION; HUMAN PAPILLORNAVIRUS HPV; GINGER SESQUITERPENE; IN-UTERO; CANCER; EXPRESSION; CHEMOPREVENTION; INHIBITORS; AGENTS;

D O I：

10.1016/j.etp.2009.06.005

中图分类号：

R36 [病理学];

学科分类号：

100104 ;

摘要：

Background: Cervical cancer is the second most common cause of cancer death in women. We have demonstrated previously that zerumbone (ZER) has an anti-cancer effect towards human cervical cancer cells (HeLa). Methods: Anti-cancer properties of ZER were investigated using female Balb/c mice exposed prenatally to diethylstilboestrol. Female offspring have been treated with ZER (4, 8 and 16 mg/kg), normal saline and cisplatin (10 mg/kg; positive control). The anti-cancer properties of ZER were evaluated using histopathology, TdT-mediated dUTP nick end labeling (TUNEL) Assay and immunhistochemical staining of Bcl-2-associated X protein (Bax), a key protein in mitochondrial pathway of apoptosis. In addition, laser capture microdissection microscopy isolated RNA was amplified using reverse transcriptase polymerase chain reaction (RT-PCR) based on the specific primer of B-cell lymphoma 2 (Bcl-2). Results: Treatment with ZER resulted (P<0.05, chi(2) statistics) in the regression of cervical intraepithelial neoplasia (CIN) resembling cisplatin effect (10 mg/kg). TUNEL micrographs showed the absence of apoptosis in cancerous tissues treated with normal saline compared to ZER and cisplatin where abundant apoptotic cells were noticed. A post hoc analysis showed a significant (P<0.01) difference in mean percentage of apoptosis between normal saline treatment (0%), ZER (15.7%) and cisplatin (21.7%). Immunohistochemical staining of Bax protein revealed that ZER modulates the expression of this apoptosis marker. Administration of ZER has also modulated the expression of Bcl-2 gene. Conclusion: These findings showed that ZER induces apoptosis efficiently in cervical tissues from female Balb/c mice treated prenatally with diethylstilboestrol. This suggested that ZER, a plant-derived compound, could be introduced as a new chemo-preventive agent for CIN in future. (C) 2009 Elsevier GmbH. All rights reserved.

引用

页码：461 / 469

页数：9

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