Decrease in drug accumulation and in tumour aggressiveness marker expression in a fenretinide-induced resistant ovarian tumour cell line

Appierto, Valentina; Cavadini, Elena; Pergolizzi, Rossana; Cleris, Loredana; Lotan, Reuben; Canevari, Silvana; Formelli, Franca

doi:10.1054/bjoc.2001.1826

Cited by 34 publications

(59 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We demonstrated that in A2780, a human ovarian carcinoma cell line sensitive to the apoptotic effect of the retinoid, HPR-induced apoptosis is accompanied by elevation of c-Fos at mRNA and protein levels. In contrast, the increase in c-Fos expression was not observed when HPR-resistant cells (A2780/HPR), developed by continuous in vitro exposure to HPR of A2780 cells, 29 were treated with HPR. In other human ovarian cancer cell lines (SKOV-3, OVCA-432, OAW-42, and IGROV-1), which required for growth inhibition higher HPR doses than A2780 cells, c-Fos upregulation occurred but only at high effective doses of HPR.…”

Section: Discussionmentioning

confidence: 85%

“…We previously showed that the human ovarian carcinoma cell line A2780 is very sensitive to apoptosis induction by HPR treatment, 4 and that A2780 cells become resistant to HPR action (A2780/ HPR) when continuously exposed to the retinoid. 29 We also reported that HPR was able to induce ceramide levels in sensitive but not in resistant cells. 22 Using A2780 and A2780/ HPR cells and a panel of other human ovarian cancer cell lines, we examined the effects of HPR treatment on c-Fos expression to determine the role of the proto-oncogene in HPR-induced apoptosis.…”

Section: Introductionmentioning

confidence: 71%

“…c-Fos mRNA expression was also analyzed in A2780 cells treated for 24 h with 5 mM RA or 5 mM 13-cis-retinoic acid (13-cis-RA), two retinoids we previously demonstrated to have no growth inhibitory effects on A2780 cells. 29 c-Fos expression was not affected by the two retinoids ( Figure 1e).…”

Section: Hpr Effect On C-fos Expression In A2780 and A2780/hpr Cellsmentioning

confidence: 91%

“…29 As shown in Figure 1a, treatment of A2780 cells with 5 and 10 mM HPR for 24 h resulted in a dose-dependent induction of apoptosis, as measured by the terminal dUTP nick-end labeling (TUNEL) assay. c-Fos mRNA expression, analyzed by reverse transcription polymerase chain reaction (RT-PCR) in A2780 cells, showed that A2780 cells constitutively expressed c-Fos mRNA, and that HPR treatment increased its expression (Figure 1b and c).…”

Section: Hpr Effect On C-fos Expression In A2780 and A2780/hpr Cellsmentioning

confidence: 94%

“…As we previously reported, 29 the A2780/HPR cell line was generated by in vitro incubation of A2780 cells with increasing concentrations of HPR. …”

Section: Hpr Effect On C-fos Expression In A2780 and A2780/hpr Cellsmentioning

confidence: 99%

See 4 more Smart Citations

Involvement of c-Fos in fenretinide-induced apoptosis in human ovarian carcinoma cells

et al. 2003

Self Cite

View full text Add to dashboard Cite

Fenretinide (HPR), a synthetic retinoid that exhibits lower toxicity than other retinoids, has shown preventive and therapeutic activity against ovarian tumors. Although the growth inhibitory effects of HPR have been ascribed to its ability to induce apoptosis, little is known about the molecular mechanisms involved. Since the proto-oncogene c-Fos has been implicated in apoptosis induction, we analyzed its role in mediating HPR response in a human ovarian carcinoma cell line (A2780) sensitive to HPR apoptotic effect. In these cells, HPR treatment caused induction of c-Fos expression, whereas such an effect was not observed in cells made resistant to HPR-induced apoptosis (A2780/HPR). Moreover, in a panel of other human ovarian carcinoma cell lines, c-Fos inducibility and HPR sensitivity were closely associated. Ceramide, which is involved in HPR-induced apoptosis, was also involved in cFos induction because its upregulation by HPR was reduced by fumonisin B 1 , a ceramide synthase inhibitor. The causal relationship between c-Fos induction and apoptosis was established by the finding of an increased apoptotic rate in cells overexpressing c-Fos. Similarly to that observed for c-Fos expression, HPR treatment increased c-Jun expression in HPR-sensitive but not in HPR-resistant cells, suggesting the involvement of the transcription factor activating protein 1 (AP-1) in HPR-induced apoptosis. In gene reporter experiments, HPR stimulated AP-1 transcriptional activity and potentiated the AP-1 activity induced by 12-tetradecanoylphorbol 13-acetate. Furthermore, inhibition of AP-1 DNA binding, by transfecting A2780 cells with a dominantnegative Fos gene, caused decreased sensitivity to HPR apoptotic effects. Overall, the results indicate that c-Fos plays a role in mediating HPR-induced growth inhibition and apoptosis in ovarian cancer cells and suggest that c-Fos regulates these processes as a member of the AP-1 transcription factor.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 71%

Section: Hpr Effect On C-fos Expression In A2780 and A2780/hpr Cellsmentioning

confidence: 91%

Section: Hpr Effect On C-fos Expression In A2780 and A2780/hpr Cellsmentioning

confidence: 94%

“…As we previously reported, 29 the A2780/HPR cell line was generated by in vitro incubation of A2780 cells with increasing concentrations of HPR. …”

Section: Hpr Effect On C-fos Expression In A2780 and A2780/hpr Cellsmentioning

confidence: 99%

See 3 more Smart Citations

Involvement of c-Fos in fenretinide-induced apoptosis in human ovarian carcinoma cells

et al. 2003

Self Cite

View full text Add to dashboard Cite

show abstract

A survey of intensity‐modulated radiation therapy use in the United States

Mell

Roeske

Mundt

2003

Cancer

View full text Add to dashboard Cite

The interfacial area of mass transfer is one of the key parameters in valve tray design, and the valve geometry is the important structural parameter that determines the interfacial area. In this work, the hydrodynamic and mass‐transfer characteristics of three different types of valve trays are investigated. The mechanism of bubbles deformation and breakage in the turbulent dispersion system is theoretically analyzed on the basis of Kolmogoroff's isotropic turbulence hypothesis, and a novel model is proposed to predict the interfacial area. The results show that the simulation results agree well with the experimental data. In contrast to most of the conventional models, the present model is capable of evaluating the effects of valve configuration on the interfacial area. The model is expected to guide effectively the design of valve trays which is widely applied nowadays. © 2008 American Institute of Chemical Engineers AIChE J 2008

show abstract

Is growth inhibition and induction of apoptosis in lung cancer cell lines by fenretinide [N‐(4‐hydroxyphenyl)retinamide] sufficient for cancer therapy?

Ohlmann

Jung

Jaques

2002

Intl Journal of Cancer

View full text Add to dashboard Cite

Key words: lung cancer; fenretinide; retinoids; proliferation; apoptosis; cancer therapyLung cancer rates have declined over the past decade, due to less consumption of tobacco. Lung cancer will also fall behind prostate and breast cancer as being the most frequent cancer incidences in the United States. 1,2 Despite this, the prognosis of lung cancer is still very poor, due to the fact that advances in therapy have not been made during the last years. The development of new treatment strategies is urgently needed to improve prognosis in the future. 1 Retinoids are natural and synthetic derivatives of vitamin A, which effect several physiologic functions, including control of proliferation and differentiation in epithelial tissue. Since alterations in the retinoid signalling pathways have been implicated in the pathogenesis of lung cancer, 3,4 retinoids have been investigated as possible agents for chemoprevention and therapy of lung cancer. 5,6 Several studies showed that all-trans-retinoic acid (ATRA), being the most active natural retinoid, failed to inhibit growth in many small cell lung cancer (SCLC) as well as nonsmall cell lung cancer (NSCLC) cell lines. Even growth stimulation has been observed in 2 cell lines. 4 Furthermore, ATRA showed only little activity against metastatic NSCLC in phase II of a clinical trial. 7 Therefore, other retinoids were investigated with the emphasis on synthetic retinoids, which imitate the growth inhibitory effects of ATRA and have lower toxicity than the natural retinoids. N-(4-hydroxyphenyl)retinamide) (4-HPR), a synthetic amide of ATRA, seems to be a promising retinoid that combines both features. 4-HPR has been shown to be a more potent growth inhibitor than ATRA in a variety of cancer cell lines, including lung cancer cell lines. 8 Whereas ATRA inhibits growth of cancer cell lines by induction of differentiation, 4-HPR has the ability to induce apoptosis selectively in these cell lines. 9 In the first clinical trials, 4-HPR exhibited low toxicity in humans and is currently under investigation in several other clinical trials. 8 Despite these encouraging results, some features of 4-HPR may limit clinical use, either as a chemopreventive agent or in the therapy of patients with solid tumours. On the one hand, the effect of 4-HPR on the growth of cancer cells has been shown to be reversible upon its removal in some cell lines, which requires long-term administration in patients to achieve the desired effect. 10,11 On the other hand, a recent study showed an acquired 4-HPR-induced resistant ovarian tumour cell line, after exposure to increasing concentrations of 4-HPR. 12 The aim of our study was to have a close look at the effect of 4-HPR on the growth of lung cancer cell lines, especially with regard to the clinical use in lung cancer patients. Therefore, we investigated the effect of 4-HPR on the growth of a broad panel of SCLC cell lines and NSCLC cell lines in order to see whether its inhibitory effect is a common phenomenon in lung cancer cell lines. We further compar...

show abstract

Decrease in drug accumulation and in tumour aggressiveness marker expression in a fenretinide-induced resistant ovarian tumour cell line

Cited by 34 publications

References 16 publications

Involvement of c-Fos in fenretinide-induced apoptosis in human ovarian carcinoma cells

Involvement of c-Fos in fenretinide-induced apoptosis in human ovarian carcinoma cells

A survey of intensity‐modulated radiation therapy use in the United States

Is growth inhibition and induction of apoptosis in lung cancer cell lines by fenretinide [N‐(4‐hydroxyphenyl)retinamide] sufficient for cancer therapy?

Contact Info

Product

Resources

About