Carnitine sensitizes TRAIL-resistant cancer cells to TRAIL-induced apoptotic cell death through the up-regulation of Bax

Park, Soo‐Young; Kim, Joo-Oh; Kim, Jung Ho; Hwang, Jung Jin; Jin, Dayong; Jeong, Seong‐Yun; Lee, Seung Jin; Kim, Jin Cheon; Kim, InKi; Cho, Dong‐Hyung

doi:10.1016/j.bbrc.2012.10.038

Cited by 15 publications

(6 citation statements)

References 36 publications

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“…Besides, the apoptotic features such as nuclear chromatin condensation and cell shrinkage were observed through the histochemical staining in TRAIL- and TZT-treated MDA-MB-231. This agrees with other studies in which Zeb and TSA respectively augmented the TRAIL-induced apoptosis in cancerous cells through elevation of fucosylation level of death receptors (Moriwaki et al., 2010) and downregulation of anti-apoptotic proteins Bcl-2 (Billam et al., 2010; Park et al., 2009, 2012). Furthermore, other studies illustrated the additive effects by various sensitizers augmented TRAIL-induced apoptosis through the downregulation of cFLIP (Carlisi et al., 2009; Manouchehri et al., 2018), the reversal of DR internalizations (Moriwaki et al., 2010; Twomey et al., 2015) and the decreased expression of anti-apoptotic proteins (Hari et al., 2015; Park et al., 2014).…”

Section: Discussionsupporting

confidence: 93%

Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis

Kong

Yee

et al. 2019

Heliyon

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Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising cancer therapeutic agent due to its selective killing on cancer cells while sparing the normal cells. Nevertheless, breast adenocarcinoma cells can develop TRAIL resistance. Therefore, this project investigated the anti-cancer effects of the combination of epigenetic drugs zebularine and trichostatin A (ZT) with TRAIL (TZT) on the human breast adenocarcinoma cells. This treatment regimen was compared with the natural anti-cancer compound curcumin (Cur) and standard chemotherapeutic drug doxorubicin (Dox). As compared to TRAIL treatment, TZT treatment hampered the cell viability of human breast adenocarcinoma cells MDA-MB-231 significantly but not MCF-7 and immortalized non-cancerous human breast epithelial cells MCF10A. Unlike TZT, Cur and Dox treatments reduced cell viability in both human breast adenocarcinoma and epithelial cells significantly. Nevertheless, there were no changes in cell cycle in both TRAIL and TZT treatments in breast adenocarcinoma and normal epithelial cells. Intriguingly, Cur and Dox treatment generally induced G2/M arrest in MDA-MB-231, MCF-7 and MCF10A but Cur induced S phase arrest in MCF10A. The features of apoptosis such as morphological changes, apoptotic activity and the expression of cleaved poly (ADP) ribose polymerase (PARP) protein were more prominent in TRAIL and TZT-treated MDA-MB-231 as compared to MCF10A at 24 h post-treatment. Compared to TZT treatment, Cur and Dox treatments exhibited lesser apoptotic features in MDA-MB-231. Collectively, the sensitization using Zeb and TSA to augment TRAIL-induced apoptosis might be an alternative therapy towards human breast adenocarcinoma cells, without harming the normal human breast epithelial cells.

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Section: Discussionsupporting

confidence: 93%

Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis

Kong

Yee

et al. 2019

Heliyon

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“…Previous studies have suggested that targeting death receptors and their respective signaling pathways to trigger apoptosis promotes the sensitivity of tumor cells ( 29 , 39 , 40 ). A variety of agents such as delphinidin ( 39 ), ursolic acid ( 40 ), carnitine ( 41 ), salirasib ( 42 ), monensin ( 43 ) and 2-tellurium-bridged β-cyclodextrin ( 44 ), have been demonstrated to sensitize tumors to apoptosis by inducing DR5. In the present study, it was identified that RAB increased the mRNA and protein levels of DR5 in PCa cells.…”

Section: Discussionmentioning

confidence: 99%

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells

Liu

Yue

et al. 2017

Oncol Lett

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Retigeric acid B (RAB), a natural compound isolated from lichen, has been demonstrated to inhibit cell growth and promote apoptosis in prostate cancer (PCa) cells. The present study evaluated the function of RAB combined with clinical chemotherapeutic drugs in PCa cell lines by MTT assay, reverse transcription quantitative polymerase chain reaction and western blot analysis, and identified that RAB at low doses produced significant synergistic cytotoxicity in combination with cisplatin (CDDP); however, no marked synergism between RAB and the other chemotherapeutics was observed. Additional studies revealed that RAB exerted an inhibitory effect on DNA damage repair pathways, including the nucleotide excision repair and mismatch repair pathways, which are involved in the sensitivity to CDDP-based chemotherapy, as suggested by the significantly downregulated expression of certain associated repair proteins. Notably, Excision repair cross-complementing 1, a critical gene in the nucleotide excision repair pathway, exhibited the most significant decrease. When combined with CDDP, RAB-mediated impairment of DNA repair resulted in prolonged DNA damage, as demonstrated by the long-lasting appearance of phosphorylation of histone H2AX at Ser139, which potentially enhanced the chemosensitivity to CDDP. Concurrently, the proapoptotic protein death receptor 5 (DR5) was activated by RAB, which also enhanced the chemotherapeutic response of CDDP. Knockdown of DR5 partially blocked RAB-CDDP synergism, suggesting the crucial involvement of DR5 in this event. The results of the present study identified that RAB functioned synergistically with CDDP to increase the efficacy of CDDP by inhibiting DNA damage repair and activating DR5, suggesting the mechanistic basis for the antitumor effect of RAB in combination with current chemotherapeutics.

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“…Novel agents, such as natural compounds, are needed to overcome this resistance and to improve TRAIL efficacy. Recently, a variety of agents, such as various types of isoflavones [ 30 ], ursolic acid [ 31 ], carnitine [ 32 ], salirasib [ 33 ], monensin [ 34 ], and 2-tellurium-bridged β-cyclodextrin [ 35 ], have been reported to sensitize tumors to TRAIL-induced apoptosis. Recently, cancer prevention research reports have shown that chemopreventive agents, such as curcumin, EGCG (epigallocatechin gallate), and resveratrol, have the therapeutic potential to sensitize prostate cancer cells to TRAIL [ 36 - 38 ].…”

Section: Introductionmentioning

confidence: 99%

Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by inducing DR5 and causing caspase-mediated HDAC3 cleavage

Jeong

Jeon

et al. 2015

Oncotarget

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TRAIL can induce apoptosis in some cancer cells and is an immune effector in the surveillance and elimination of developing tumors. Yes, some cancers are resistant to TRAIL. Delphinidin, a polyphenolic compound contained in brightly colored fruits and vegetables, has anti-inflammatory, anti-oxidant, and anti-tumorigenic activities. Here we showed that delphinidin sensitized TRAIL-resistant human prostate cancer cells to undergo apoptosis. Cells treated with delphinidin and TRAIL activated the extrinsic and intrinsic pathways of caspase activation. TRAIL-induced apoptosis in prostate cancer cells pretreated with delphinidin was dependent on death receptor 5 (DR5) and downstream cleavage of histone deacetylase 3 (HDAC3). In conclusion, delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis by inducing DR5, thus causing caspase-mediated HDAC3 cleavage. Our data reveal a potential way of chemoprevention of prostate cancer by enabling TRAIL-mediated apoptosis.

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Carnitine sensitizes TRAIL-resistant cancer cells to TRAIL-induced apoptotic cell death through the up-regulation of Bax

Cited by 15 publications

References 36 publications

Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis

Zebularine and trichostatin A sensitized human breast adenocarcinoma cells towards tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-induced apoptosis

Enhancement of cisplatin cytotoxicity by Retigeric acid B involves blocking DNA repair and activating DR5 in prostate cancer cells

Delphinidin sensitizes prostate cancer cells to TRAIL-induced apoptosis, by inducing DR5 and causing caspase-mediated HDAC3 cleavage

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