Cited 0 times in Scipus Cited Count

Effect of Combination of Aspirin and TRAIL in HeLa Cervical Cancer Cells

Other Title
Aspirin과 TRAIL 병합처리시 자궁경부암인 HeLa cell에 미치는 영향
Authors
임, 세란
Department
대학원 의생명과학과
Degree
Master (2012)
Abstract
Purpose: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor (TNF) family of cytokines and induces apoptosis in most tumor cells. Although TRAIL is considered a promising drug for cancer therapies because of its tumor selectivity, many tumors are resistant to TRAIL. Thus TRAIL-resistant cancer cells must be sensitized first to become responsive to TRAIL. In this study, I studied whether pretreatment by aspirin augmented TRAIL-induced apoptotic death in HeLa cells, which derived from cervical cancer and investigated the underlying mechanism.

Methods: Cell viability and proliferation were assessed by MTT assay and cytotoxicity was analyzed by LDH assay. Annexin-V /PI staining and sub G1 analysis were used for evaluation of apoptotic cells. We measured mitochondrial membrane potential in HeLa cells undergoing apoptosis by using JC-1. Protein level changes were documented by western blot analysis.

Results: Aspirin inhibited proliferation of HeLa cells in the time- and dose-dependent manners. The combined treatment of aspirin with TRAIL strongly enhanced TRAIL-induced apoptotic cell death in HeLa cells. It activated caspase-8, -9 and -3 and caused the caspase-dependent loss of MMP and the release of cytochrome c from mitochondria to cytosol. The apoptotic characteristics enhanced by the combined treatment were inhibited by a pan-caspase inhibitor z-VAD-fmk. Interestingly, TRAIL caused the activation of ERK, whereas the ERK activation was blocked by aspirin. As a result, the activation of ERK decreased and additionally, Mcl-1 also decreased in combination treatment.

Conclusion: TRAIL in combination with aspirin significantly increase apoptosis in HeLa cells through caspase-and mitochondrial-dependent pathway. Mechanism of such a promoted apoptotic effect might be associated with that TRAIL-induced ERK activation which triggers survival signal to HeLa cells is blocked by pretreatment of aspirin. Inhibition of ERK activation enhances TRAIL-induced caspase activation, which rapidly cleavages Mcl-1. It could also trigger translocation of cleaved Bid to mitochondria to activate mitochondrial pathway, which also amplifies caspase activation. Eventually, pre-treated aspirin could block the survival signal and enhance caspase-and mitochondrial-dependent apoptotic cell death in HeLa cells treated with TRAIL.
Appears in Collections:
Theses > Graduate School of Biomedical Sciences > Master
Ajou Authors
임, 세란
Full Text Link
Files in This Item:
There are no files associated with this item.
Export

qrcode

해당 아이템을 이메일로 공유하기 원하시면 인증을 거치시기 바랍니다.

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse