Effects of receptor class- and subtype-selective retinoids and an apoptosis-inducing retinoid on the adherent growth of the NIH:OVCAR-3 ovarian cancer cell line in culture

Chao, Wan‐Ru; Hobbs, Peter D.; Jong, Ling; Zhang, Xiaokun; Zheng, Yun; Wu, Qiao; Shroot, Braham; Dawson, Marcia I.

doi:10.1016/s0304-3835(97)04598-9

Cited by 43 publications

(49 citation statements)

References 15 publications

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“…The selectivity of these retinoids for individual RAR subtypes was originally reported by Chao et al (1997) and Dawson et al (1998) and is shown in Table 1. It is clear that at 10 76 M, MM 11254 and MM 11389 selectively activate both RAR-g and RAR-b dependent transcriptional activity but do not activate RAR-a or RXR-a dependent transcription.…”

Section: Synthetic Rar-g Selective Retinoids Inhibit Growth Of Scc-25mentioning

confidence: 87%

“…MM11253 (previously called SR11253), an RAR-g selective antagonist, (2-{(5,6,7,8-tetrahydro -5,5,8,8 -tetramethyl -2 -naphthalenyl) -2-(6 -carboxy-2-naphthalenyl)-1,3-dithiolane; MM11389 (previously called SR11389), an RAR-g selective agonist, 6-[3-(1-adamantyl)-4-hydroxyphenyl]-5-methyl-2-naphthalenylcarboxylic acid and MM11254 (previously called SR11254), an RAR-g selective agonist, E -6 -{ (5 ,6, 7, 8 -tetrahydro -5, 5, 8, 8 -tetramethyl -2 -naphthalenyl) (hydroxyimino) methyl] -2 -naphthalenecarboxylic acid have been described previously (Chao et al, 1997;Sun et al, 1997;Dawson et al, 1998). All of the synthetic retinoids were prepared at the Molecular Medicine Research Institute (Mountain View, CA, USA).…”

Section: Cell Culture and Reagentsmentioning

confidence: 99%

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Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids

Dawson

Soprano

et al. 2000

Oncogene

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Section: Synthetic Rar-g Selective Retinoids Inhibit Growth Of Scc-25mentioning

confidence: 87%

Section: Cell Culture and Reagentsmentioning

confidence: 99%

Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids

Dawson

Soprano

et al. 2000

Oncogene

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“…Interest in retinoids as a potential chemotherapeutic agent arises from the fact that the growth of a number of tumor cells is suppressed by treatment with ATRA. More specifically, the ability of retinoids to inhibit the growth and cell cycle progression of ovarian carcinoma cell lines has been studied by a number of laboratories including our own (Grunt et al, 1991;Harant et al, 1993;Saunders et al, 1995;Chao et al, 1997;Wu et al, 1997aWu et al, , b, 1998aSabichi et al, 1998;Pergolizzi et al, 1999;Um et al, 2001;Zhang et al, 2001). …”

Section: Effects Of Retinoids On Cancer Cellsmentioning

confidence: 99%

Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid

et al. 2006

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Despite a number of attempts to improve treatment of ovarian cancer, it remains the most common cause of death from gynecological cancers. Thus, it is very important to identify more effective drugs for treatment and prevention of ovarian cancer. All-trans-retinoic acid (ATRA) has been shown to arrest the growth of ovarian carcinoma cells in G0/G1 and to significantly elevate levels of Rb2/p130 protein, a member of the retinoblastoma family of tumor suppressors. As ATRA treatment leads to a significant increase in the amount of Rb2/p130 protein but not mRNA, the elevated levels of Rb2/p130 protein is likely the result of increased stability. In studies to elucidate the mechanism by which ATRA alters Rb2/ p130 stability in ovarian cancer cells, it was determined that PP2A, a serine/threonine phosphatase, binds and dephosphorylates Rb2/p130. Dephosphorylated Rb2/p130 exhibits decreased ubiquitination and thus is not degraded by the proteasome. The sites at which PP2A catalytic subunit (PP2Ac) interacts with Rb2/p130 have been localized to the NLS in the C-terminus of Rb2/p130. These sites are also involved in the interaction of Rb/p130 with importin b and importin a, members of the nuclear transport machinery. It is known that importin a recognizes a NLS on a target protein and importin b binds the nuclear pore complex. Moreover, it has been shown that the binding of importin a to NLS significantly decreases with phosphorylation of NLS. In ATRA-treated ovarian carcinoma cells, PP2A binds to Rb2/p130 and dephosphorylates the NLS of Rb2/p130 leading to the interaction of importin a with Rb2/p130. Importin b then binds to the importin a-Rb2/p130 complex, leading to the translocation of the Rb2/p130 to the nucleus where it acts to arrest ovarian cancer cells in G1 and suppress proliferation.

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“…AHPN binds and transactivates both the RAR␤ and RAR␥ receptors. 22,23 The roles of these retinoid nuclear receptors in AHPN-mediated apoptosis are controversial. While some studies have suggested that binding and transactivation of RAR␥ are essential for AHPN/CD437-mediated apoptosis, 24,25 others have indicated that neither the RARs nor the retinoid X receptors (RXRs) to which AHPN does not bind or transactivate are involved.…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis in retinoid-refractory acute myelogenous leukemia by a novel AHPN analog

Zhang

Dawson²,

Ning³

et al. 2003

Blood

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IntroductionAcute myelogenous leukemia (AML) is a heterogeneous disease composed of numerous subclassifications displaying a wide spectrum of phenotypes. 1,2 The major therapeutic approach to this disease has been the use of chemotherapeutic agents with associated life-threatening toxicity. Although nonspecific in their effects, these regimens have significantly increased the survival of AML patients. [3][4][5] Recently, more targeted therapy has been developed. Treatment of acute promyelocytic leukemia (APL) patients with trans-retinoic acid (tRA) results in the differentiation of the leukemic cells, with 90% of the patients achieving a complete remission. [6][7][8] The tRA exerts its effect by modulating gene expression through its role as a ligand to the retinoic acid nuclear receptors, RARs, with the subsequent binding of this complex to the retinoic acid response element (RARE) consensus sequences located in the regulatory regions of retinoid-responsive genes. 9 The selective sensitivity of APL cells to tRA-mediated differentiation resides in their specific expression of a unique promyelocytic leukemia (PML)-RAR␣ fusion product that results in the subsequent maturation arrest of these cells at the promyelocyte stage [10][11][12] ; exposure of these cells to a micromolar concentration of tRA allows for the degradation of the PML-RAR␣ fusion product, with subsequent maturation of the APL cells. [13][14] Unfortunately, the other AML subtypes as classified by the French-American-British (FAB) classification demonstrate inherent resistance to tRA-mediated differentiation and induction of apoptosis. 15,16 We and others have recently described a novel retinoid 6-[3-(1-adamantyl)-4-hydroxyphenyl]-2-naphthalenecarboxylic acid (AHPN/CD437), which is a potent inducer of apoptosis in a variety of cell types and which displays resistance to tRA-mediated differentiation and apoptosis. [17][18][19][20][21] The mechanistic pathways by which AHPN induces apoptosis in malignant cells are not clearly defined. AHPN binds and transactivates both the RAR␤ and RAR␥ receptors. 22,23 The roles of these retinoid nuclear receptors in AHPN-mediated apoptosis are controversial. While some studies have suggested that binding and transactivation of RAR␥ are essential for AHPN/CD437-mediated apoptosis, 24,25 others have indicated that neither the RARs nor the retinoid X receptors (RXRs) to which AHPN does not bind or transactivate are involved. 20,21,26 bloodjournal.org FromIn the present study, we assessed the ability of the AHPN analog 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid (3-Cl-AHPC/MM002) to induce apoptosis in a number of human AML cell lines as well as in primary cultures of leukemic blasts obtained from patients. The 3-Cl-AHPC differs from AHPN in its inability to recruit RAR coactivators and transactivate the RARs (Zhang et al 27 and data not shown). We found that 3-Cl-AHPC is a potent inducer of apoptosis in these cells, which display resistance to the antiproliferative/differentiating effects of tRA. The 3-C...

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Effects of receptor class- and subtype-selective retinoids and an apoptosis-inducing retinoid on the adherent growth of the NIH:OVCAR-3 ovarian cancer cell line in culture

Cited by 43 publications

References 15 publications

Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids

Modulation of retinoic acid receptor function alters the growth inhibitory response of oral SCC cells to retinoids

Rb2/p130 and protein phosphatase 2A: key mediators of ovarian carcinoma cell growth suppression by all-trans retinoic acid

Induction of apoptosis in retinoid-refractory acute myelogenous leukemia by a novel AHPN analog

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