Viability of Cultured Lewis Lung Cell Populations Exposed to  -Retinoic Acid

Wilkoff, Lee J.; Dulmadge, Elizabeth A.; Chopra, Dharam P.

doi:10.3181/00379727-163-40753

Cited by 23 publications

(15 citation statements)

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“…JL D is a doxorubicin-resistant line, primarily by virtue of altered levels of topo II but probably also by additional mechanisms. LLTC is a murine Lewis lung carcinoma line, 30 included as a solid tumor model. Absolute IC 50 values are given for the P388, LLTC, and JL C lines, together with ratios of IC 50 values against JL C and the other two Jurkat lines (ratios JL A /JL C and JL D /JL C ).…”

Section: Resultsmentioning

confidence: 99%

“…In V itro G rowth D elay A ssays. Murine P388 leukemia cells, Lewis lung carcinoma cells (LLTC), and human Jurkat leukemia cells (JL C ), together with their amsacrine- and doxorubicin-resistant derivatives (JL A and JL D , respectively), were obtained and cultured as described. , Growth inhibition assays were performed by culturing cells at 4.5 × 10 3 (P388), 10 3 (LLTC), and 3.75 × 10 3 (Jurkat lines) cells/well in microculture plates (150 mL/well) for 3 (P388) or 4 days in the presence of drug. Cell growth was determined by [ 3 H]TdR uptake (P388) or the sulforhodamine assay .…”

Section: Methodsmentioning

confidence: 99%

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Structure−Activity Relationships for Substituted Bis(acridine-4-carboxamides): A New Class of Anticancer Agents

et al. 1999

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A series of acridine-substituted bis(acridine-4-carboxamides) linked by a (CH2)3N(Me)(CH2)3 chain have been prepared by reaction of the isolated imidazolides of the substituted acridine-4-carboxylic acids with N,N-bis(3-aminopropyl)methylamine. These dimeric analogues of the mixed topoisomerase I/II inhibitor N-[2-(dimethylamino)ethyl]acridine-4-carboxamide (DACA), currently in clinical trial, show superior potencies to the corresponding monomeric DACA analogues in a panel of cell lines, including wild-type (JLC) and mutant (JLA and JLD) forms of human Jurkat leukemia. The latter mutant lines are resistant to topoisomerase II targeted agents because of lower levels of the enzyme. Analogues with small substituents (e.g., Me, Cl) at the acridine 5-position were clearly superior, with IC50's as low as 2 nM against the Lewis lung carcinoma and 11 nM against JLC. Larger substituents at any position caused a steady decrease in potency, likely due to lowering of DNA binding affinity. A small series of analogues of the most potent bis(5-methylDACA) compound, with second substituents (Me and Cl) in the 1- or 8- position had broadly similar potencies to the 5-Me compound, indicating that, while the 1- and 8-substituents are acceptable, they add little to the enhancing effect of the 5-methyl group. All of the compounds were at least equitoxic (some up to 4-fold more cytotoxic) against the mutant Jurkat lines than in the wild-type, consistent with a relatively greater effect on topoisomerase I compared with topoisomerase II. The bis(5-methylDACA) compound was found to inhibit the action of purified topoisomerase I in a cell-free assay. Compounds were on average 10-fold less cytotoxic in an MCF7 breast cancer line overexpressing P-glycoprotein than in the wild-type line and showed some selectivity for colon tumor lines in the NCI human tumor cell line panel. Several analogues produced significant growth delays in the relatively refractory subcutaneous colon 38 tumor model in vivo at substantially lower doses than DACA. The bis(acridine-4-carboxamides) represent a new and interesting class of potent topoisomerase inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Structure−Activity Relationships for Substituted Bis(acridine-4-carboxamides): A New Class of Anticancer Agents

et al. 1999

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“…Di-Me-PGA , and di-Me-PGA, inhibition of DNA synthesis is as effective on a molar basis as retinoic acid inhibition of B 16 melanoma cell proliferation (18) and 25 times more effective when compared to retinoic acid effects upon 3LL tumor cell proliferation (19). Di-Me-PGE, is also more effective than di-Me-PGE, in both systems.…”

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confidence: 89%

Prostaglandin Analogs as Inhibitors of Tumor Cell DNA Synthesis

Honn¹,

Romine²,

Skoff³

1981

Experimental Biology and Medicine

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D e p u rt m en t J of Radio logy, Rudiu t ion Oncology u nd Biolog icu I Scien ces . Wu y n c St N t e University , Detroit. Michigun 48202~~ Abstracr. Analogs of the A and E series prostaglandins were screened in vitro for their chemotherapeutic potential against Lewis lung carcinoma and B 16 amelanotic melanoma cells, since in vivo studies had demonstrated that PGA, and an analog of PGE., inhibited tumor growth. DNA synthesis by collagenase-dispersed tumor cells was evaluated at timed intervals after exposure to the 16, 16-dimethyl analogs of PGA,, PGA2, PGE,, and PGE.,. In general, the PGA derivatives were more potent than the PGE analogs. However, the maximum effect was achieved with combined PGA and PGE treatment. These findings 562

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“…Historically, natural retinoids have been used in the treatment of lung cancers since the late 70's when the first human trials were conducted [4], [5], [6], [7] on the basis of antiproliferative effects specific to epithelial tissues and tumors [8], [9], [10], [11]. The development of synthetic retinoids occurred subsequently in an attempt to retain vitamin A's antiproliferative effects specific to epithelial tissue while avoiding dose limiting side effects such as skin and liver toxicity [4], [12].…”

Section: Introductionmentioning

confidence: 99%

Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis

et al. 2011

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BackgroundDespite reported antiproliferative activity of vitamin A and its common use for cancer, there is no comprehensive synthesis of its safety and efficacy in lung cancers. To address this issue we conducted a systematic review of the safety and efficacy of vitamin A for the treatment and prevention of lung cancers.Methods and FindingsTwo independent reviewers searched six electronic databases from inception to July 2009 for clinical, observational, and preclinical evidence pertaining to the safety and efficacy of vitamin A and related retinoids for lung cancers. 248 studies were included for full review and analysis. Five RCTs assessed treatment of lung cancers, three assessed primary prevention, and three looked at secondary prevention of lung cancers. Five surrogate studies, 26 phase I/II, 32 observational, and 67 preclinical studies were also included. 107 studies were included for interactions between vitamin A and chemo- or radiation- therapy. Although some studies demonstrated benefits, there was insufficient evidence overall to support the use of vitamin A or related retinoids for the treatment or prevention of lung cancers. Retinyl palmitate combined with beta carotene increased risk of lung cancer in smokers in the large CARET trial. Pooling of three studies pertaining to treatment and three studies on secondary prevention revealed no significant effects on response rate, second primary tumor, recurrence, 5-year survival, and mortality. There was a small improvement in event free survival associated with vitamin A compared to controls, RR 1.24 (95% CI 1.13–1.35). The synthetic rexinoid bexarotene increased survival significantly among a subset of patients in two RCTs (p<0.014, <0.087).ConclusionsThere is a lack of evidence to support the use of naturally occuring retinoids for the treatment and prevention of lung cancers. The rexinoid bexarotene may hold promise for use among a subset of patients, and deserves further study.

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Viability of Cultured Lewis Lung Cell Populations Exposed to -Retinoic Acid

Cited by 23 publications

References 0 publications

Structure−Activity Relationships for Substituted Bis(acridine-4-carboxamides): A New Class of Anticancer Agents

Structure−Activity Relationships for Substituted Bis(acridine-4-carboxamides): A New Class of Anticancer Agents

Prostaglandin Analogs as Inhibitors of Tumor Cell DNA Synthesis

Vitamin A and Retinoid Derivatives for Lung Cancer: A Systematic Review and Meta Analysis

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