HT-29 colorectal cancer cells undergoing apoptosis overexpress COX-2 to delay ursolic acid-induced cell death

Limami, Youness; Pinon, Aline; Léger, David Y.; Mousseau, Yoanne; Cook-Moreau, Jeanne; Beneytout, Jean-Louis; Delage, Christiane; Liagre, Bertrand; Simon, Alain

doi:10.1016/j.biochi.2011.01.003

Cited by 47 publications

(22 citation statements)

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“…Furthermore, we showed recently that COX-2 positively regulated Akt signalling and enhanced survival of cancer cells exposed to anticancer agents (35). Numerous studies have shown that COX-2 expression prevents apoptosis in cancer cells, especially in colon (49,50) and prostate cancer (51)(52)(53). Here, we showed that Bl extract reduced significantly expression of COX-2 by a dose-dependent manner at 48-h treatment in HEL and K562 (COX-2 + ) cells (Fig.…”

Section: Resultssupporting

confidence: 57%

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

Diab

Fidanzi

Léger

et al. 2015

International Journal of Oncology

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Abstract. The aim of this study was to describe and understand the relationship between cyclooxygenase-2 (COX-2) expression and apoptosis rate in erythroleukemia cells after apoptosis induction by Berberis libanotica (Bl) extract. To achieve this goal we used erythroleukemia cell lines expressing COX-2 (HEL cell line) or not (K562 cell line). Moreover, we made use of COX-2 cDNA to overexpress COX-2 in K562 cells. In light of the reported chemopreventive and chemosensitive effects of natural products on various tumor cells and animal models, we postulated that our Bl extract may mediate their effects through apoptosis induction with suppression of cell survival pathways. Our study is the first report on the specific examination of intrinsic apoptosis and Akt/NF-κB/COX-2 pathways in human erythroleukemia cells upon Bl extract exposure. Even if Bl extract induced apoptosis of three human erythroleukemia cell lines, a dominant effect of Bl extract treatment on K562 cells was observed resulting in activation of the late markers of apoptosis with caspase-3 activation, PARP cleavage and DNA fragmentation. Whereas, we showed that Bl extract reduced significantly expression of COX-2 by a dose-dependent manner in HEL and K562 (COX-2 + ) cells. Furthermore, in regard to our results, it is clear that the simultaneous inhibition of Akt and NF-κB signalling can significantly contribute to the anticancer effects of Bl extract in human erythroleukemia cells. We observed that the Bl extract is clearly more active than the berberine alone on the induction of DNA fragmentation in human erythroleukemia cells.

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Section: Resultssupporting

confidence: 57%

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

Diab

Fidanzi

Léger

et al. 2015

International Journal of Oncology

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“…COX-2 has been shown to play an important role in apoptosis resistance and carcinogenesis, particularly in colon carcinogenesis [64,65]. Previous studies in our laboratory reported a role for COX-2 in resistance to apoptosis in colorectal and prostate cancer cells [66,67]. Here, we showed that RG003 reduced COX-2 expression in PC-3 cells; this inhibition can make cells more sensitive to TRAIL treatment.…”

Section: Discussionsupporting

confidence: 56%

2′-Hydroxy-4-methylsulfonylchalcone enhances TRAIL-induced apoptosis in prostate cancer cells

Ismail¹,

Fagnere²,

Limami³

et al. 2015

Anti-Cancer Drugs

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Prostate cancer is the most common malignant cancer in men and the second leading cause of cancer deaths. Previously, we have shown that 2'-hydroxy-4-methylsulfonylchalcone (RG003) induced apoptosis in prostate cancer cell lines PC-3 and DU145. Although tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a promising anticancer agent, some cancer cells are resistant to TRAIL treatment. PC-3 and LNCaP prostatic cancer cell lines have been reported to be resistant to TRAIL-induced apoptosis. Here, we show for the first time that RG003 overcomes TRAIL resistance in prostate cancer cells. RG003 can enhance TRAIL-induced apoptosis through DR5 upregulation and downregulation of Bcl-2, PI3K/Akt, NF-κB, and cyclooxygenase-2 (COX-2) survival pathways. When used in combined treatment, RG003 and TRAIL amplified TRAIL-induced activation of apoptosis effectors and particularly activation of caspase-8 and the executioner caspase-3, leading to increased poly-ADP-ribose polymerase cleavage and DNA fragmentation in prostate cancer cells. Furthermore, we showed that RG003 reduced COX-2 expression in cells. Previously, we showed that COX-2 was involved in resistance to an apoptosis mechanism; then, its inhibition by RG003 could render cells more sensitive to TRAIL treatment. We showed that nuclear factor-κB activation was inhibited after RG003 treatment. This inhibition was correlated with reduction in COX-2 expression and induction of apoptosis. Overall, we conclude, for the first time, that RG003 can enhance TRAIL-induced apoptosis in human prostate cancer cells. The significance of our in-vitro study with RG003 and TRAIL combined is very encouraging, suggesting the relevance of testing this combined treatment in xenograft animal models.

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“…3,4 Recent studies have shown the antitumor effect of UA through induction of apoptosis and inhibition of angiogenesis. 5,6 However, the limitation of UA clinically is attributed mainly to poor solubility and lack of ability to target tumor sites. In one study, in vivo applications of UA were significantly impaired by its low solubility, which consequently led to poor pharmacokinetics.…”

Section: Introductionmentioning

confidence: 99%

Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

Zhang¹,

Zheng²,

Jing³

et al. 2015

IJN

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Previous reports have shown that ursolic acid (UA), a pentacyclic triterpenoid derived from Catharanthus trichophyllus roots, could inhibit the growth of a series of cancer cells. However, the potential for clinical application of UA is greatly hampered by its poor solubility, whereas the hydrophobicity of UA renders it a promising model drug for nanosized delivery systems. In the current study, we loaded UA into amphiphilic poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles and performed physiochemical characterization as well as analysis of the releasing capacity. In vitro experiments indicated that UA-NPs inhibited the growth of liver cancer cells and induced cellular apoptosis more efficiently than did free UA. Moreover, UA-NPs significantly delayed tumor growth and localized to the tumor site when compared with the equivalent dose of UA. In addition, both Western blotting and immunohistochemistry suggested that the possible mechanism of the superior efficiency of UA-NPs is mediation by the regulation of apoptosis-related proteins. Therefore, UA-NPs show potential as a promising nanosized drug system for liver cancer therapy.

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HT-29 colorectal cancer cells undergoing apoptosis overexpress COX-2 to delay ursolic acid-induced cell death

Cited by 47 publications

References 47 publications

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

2′-Hydroxy-4-methylsulfonylchalcone enhances TRAIL-induced apoptosis in prostate cancer cells

Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

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HT-29 colorectal cancer cells undergoing apoptosis overexpress COX-2 to delay ursolic acid-induced cell death

Cited by 47 publications

References 47 publications

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

Berberis libanotica extract targets NF-κB/COX-2, PI3K/Akt and mitochondrial/caspase signalling to induce human erythroleukemia cell apoptosis

2′-Hydroxy-4-methylsulfonylchalcone enhances TRAIL-induced apoptosis in prostate cancer cells

Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (&epsilon;-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo

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Efficient delivery of ursolic acid by poly(N-vinylpyrrolidone)-block-poly (ε-caprolactone) nanoparticles for inhibiting the growth of hepatocellular carcinoma in vitro and in vivo