N-(4-Hydroxyphenyl)-Retinamide Selectively Increases All-&lt;i&gt;Trans&lt;/i&gt; Retinoic Acid Inhibitory Effects in &lt;i&gt;HER2/neu&lt;/i&gt;-Overexpressing Breast Cancer Cells

Lim, Soo-Jeong; Gutierrez-Puente, Yolanda; Tari, Ana M.

doi:10.1159/000068567

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…The ATRA/4-HPR combination has been examined in other cancer cells. Lim et al investigated whether 4-HPR (due to its suppression of HER2/neu and/or EGFR expression) sensitized breast cancer cells to ATRA, and found that at a concentration of 1.3 µM, 4-HPR increased ATRA sensitivity in a synergistic manner in BT-474, MDA-MB-453, and MCF-7/HER2 breast cancer cells (31). Another study demonstrated the efficacy of 4-HPR in mice bearing the human ovarian carcinoma IGROV-1, and demonstrated that 4-HPR significantly enhanced the antitumor activity of cisplatin.…”

Section: Discussionmentioning

confidence: 99%

Combinational Treatment with Retinoic Acid Derivatives in Non-small Cell Lung Carcinoma In Vitro

et al. 2007

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The growth inhibitory effects of four retinoic acid (RA) derivatives, 9-cis RA, 13-cis RA, N-(4-hydroxyphenyl) retinamide (4-HPR), and all-trans retinoic acid (ATRA) were compared. In addition, the effects of various combinations of these four agents were examined on non-small cell lung carcinoma (NSCLC) cell-lines, and on the expressions of retinoic acid receptors (RARs) and retinoid X receptors (RXRs) on these cells. At the clinically achievable concentration of 1 µM, only 4-HPR inhibited the growths of H1299 and H460 cells-lines. However, retinoic acid receptor β (RARβ) expression was up-regulated on H460 and H1299 cells treated with 1 µM of ATRA, 13-cis RA, or 9-cis RA. All NSCLC cell lines showed growth inhibition when exposed sequentially to 1 µM ATRA and 0.1 µM 4-HPR. In particular, sequential treatment with 1 µM ATRA or 13-cis RA and 4-HPR markedly inhibited H1703 cell growth; these cells exhibited no basal RARβ expression and were refractory to 4-HPR. However, in NSCLC cell lines that expressed RARβ, the expressional levels of RARβ were up-regulated by ATRA alone and by sequential treatment with ATRA and 4-HPR. 4-HPR was found to be the most active of the four agents in terms of NSCLC growth-inhibition. Moreover, sequential treatments with ATRA or 13-cis RA followed by 4-HPR were found to have synergistic growth-inhibitory effects and to regulate RAR expression.

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Section: Discussionmentioning

confidence: 99%

Combinational Treatment with Retinoic Acid Derivatives in Non-small Cell Lung Carcinoma In Vitro

et al. 2007

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“…Interferon-g enhanced 4-HPR-mediated NO production in both ER-positive and ER-negative breast cancer cells, while tamoxifen increased 4-HPR-mediated NO production only in ER-positive cells [64]. Lim et al [76] reported that cyclosporin A increased the ability of 4-HPR to induce apoptosis in breast cancer cells, and this effect was correlated with increased NO production. Recently, NOSII-mediated NO production was found to be essential for the combination of 4-HPR and trastuzumab to induce apoptosis in HER2/neu-overexpressing breast cancer cells [77].…”

Section: Nitric Oxidementioning

confidence: 99%

“…MPT antagonists, such as cyclosporin A, rescued squamous carcinoma cells from the proapoptotic effects of 4-HPR [84]. In contrast, cyclosporin A increased the ability of 4-HPR to induce apoptosis in ER-positive and ER-negative breast cancer cells [76]. The role of MPT in 4-HPR-induced apoptosis in breast cancer cells has not been determined.…”

Section: Other Potential Mechanismsmentioning

confidence: 99%

How retinoids regulate breast cancer cell proliferation and apoptosis

Simeone

Tari

2004

CMLS, Cell. Mol. Life Sci.

109

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Breast cancer still remains a major problem in its incidence, morbidity and mortality; therefore, more effective strategies for its prevention are urgently needed. Retinoids, natural and synthetic derivatives of vitamin A, possess antiproliferative and proapoptotic properties, making them a promising class of chemopreventive agents against breast cancer. The efficacy of all-trans retinoic acid, 9-cis-retinoic acid, LGD1069 (Targretin, bexarotene), and N-(4-hydroxyphenyl)retinamide (fenretinide) as breast cancer chemopreventive agents is being studied. A better understanding of the molecular mechanisms of action of these agents should lead to improvements in their clinical application. In this review, we discuss the mechanisms by which retinoids exert their antiproliferative and apoptotic effects in breast cancer cells.

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“…Although Fitzgerald et al, demonstrated that the ER-negative, HER2/neu-positive cell-line SKBR3 was associated with high expression levels of RARA and response to retinoic acid (29), it appears that SKBR3 is an exception, with most of the work in this area concluding that the majority of the ATRAresistant cell-lines are associated with moderate to high levels of the HER2/neu protein (30)(31)(32). In addition, functional work has shown that high expression levels of HER2/neu are associated with resistance to ATRA (30,33), but that a synthetic analogue of ATRA, 4-hydroxyphenyl-retinamide (4HPR), can repress HER2/ neu expression, and thereby sensitise cells to ATRA.…”

Section: Discussionmentioning

confidence: 99%

Expression levels of HER2/neu and those of collocated genes at 17q12-21, in breast cancer

et al. 2012

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Abstract. HER2/neu is associated with poorer clinical outcome in breast cancer. Expression patterns of co-localised cancerassociated genes at 17q12-21 were examined using RT-PCR. The study group consisted of a 96-patient cohort. Relative quantity of mRNA expression was calculated using the comparative cycle threshold method and Qbase software. Results were analysed to detect expression patterns among the genes, and to identify associations between expression levels and clinical data. Levels of HER2/neu correlated with those of GRB7 (r=0.551, p<0.001), RARA (r=0.391, p<0.001), RPL19 (r=0.549, p<0.001) and LASP1 (r=0.399, p<0.001). GRB7 was significantly inversely associated with improved DFS at 60 months (p=0.036). RARA levels were greater in HER2/neu-positive as opposed to HER2/ neu-negative patients (p= 0.021); levels were significantly higher in ER-positive patients, relative to those who were ER-negative (p=0.003). Levels of RPL19 were significantly higher in the HER2/neu-overexpressing (p=0.010) and luminal B subtypes (p=0.007). LASP1 levels were higher in those patients who had been classified clinically as HER2/neu-positive (p=0.004). This study reaffirms the correlation between HER2/neu and the co-localised LASP1 and GRB7; the latter target may hold additional significance in addition to being a surrogate marker for HER2/neu expression. The relationship identified between RARA and ER-positivity may herald an avenue for targeted therapy of these tumours.

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N-(4-Hydroxyphenyl)-Retinamide Selectively Increases All-<i>Trans</i> Retinoic Acid Inhibitory Effects in <i>HER2/neu</i>-Overexpressing Breast Cancer Cells

Cited by 5 publications

References 26 publications

Combinational Treatment with Retinoic Acid Derivatives in Non-small Cell Lung Carcinoma In Vitro

Combinational Treatment with Retinoic Acid Derivatives in Non-small Cell Lung Carcinoma In Vitro

How retinoids regulate breast cancer cell proliferation and apoptosis

Expression levels of HER2/neu and those of collocated genes at 17q12-21, in breast cancer

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