Panel Of Human Cancer Cell Lines Research Articles

Synthesis and biological activities of fluorinated chalcone derivatives

We have designed and synthesized new 5-lipoxygenase inhibitors, fluorinated 3,4-dihydroxychalcones, and evaluated their biological activities with respect to antiperoxidation activity and in vitro antitumor activities. All fluorinated chalcones tested showed 5-lipoxygenase inhibition on rat basophilic leukemia-1 (RBL-1) cells and inhibitory action on Fe 3+-ADP induced NADPH-dependent lipid peroxidation in rat liver microsomes. The potencies were comparable or better to that of the lead 3,4-dihydroxychalcone. 6-Fluoro-3,4-dihydroxy-2′,4′-dimethoxy chalcone ( 7) was the most effective compound in the in vitro assay using a human cancer cell line panel (HCC panel) consisting of 39 systems.

In vitro cytotoxicity of the protoberberine-type alkaloids.

In vitro cytotoxic activities of 24 quaternary protoberberine alkaloids related to berberine have been evaluated using a human cancer cell line panel coupled with a drug sensitivity database. Extending the alkyl chain at position 8 or 13 strongly influenced the cytotoxic activity, that is, relative lipophilicity as well as the size of the substituent affects cytotoxicity. The highest level of activity was observed in 8- or 13-hexyl-substituted derivatives of berberine. Structure-activity relationships are described.

Knigth′s Move in the Periodic Table, From Copper to Platinum,Novel Antitumor Mixed Chelate Copper Compounds, Casiopeinas,Evaluated by an in Vitro Human and Murine Cancer Cell Line Panel

We synthesized a novel anticancer agents based on mixed chelate copper (II) complexes, named Casiopeínas® has of general formula [Cu(N-N)(N-O)H2O]NO3 (where, N-N = diimines as 1,10- phenanthroline, 2,2-bipyridine, or substituted and N-O=aminoeidate or [Cu(N-N)(O-O)H2O]NO3 (where NN= diimines as 10-phenanthroline, 2,2-bipyridine or substituted Casiopeínas I, II, IV, V, VI, VII VIII and O-O=acetylacetonate, salicylaldehidate Casiopínas III). We evaluated the in vitro antitumor activity using a human cancer cell panel and some nurine cancer cells. Eleven Casiopeinas are evaluated in order to acquire some structure-activity correlations and some monodentated Casiopeinäs analogues; cisplatinum was used as control drug. The 50% growth inhibition observed is, in all cases reach with concentrations of Casiopeina's 10 or 100 times lower than cisplatinum. In a previous work we reported the induction of apoptosis by Casiopeina II. The results indicate that Casiopeinass are a promising new anticancer drug candidates to be developed further toward clinical trials.

Antineoplastic agents. 398. Isolation and structure elucidation of cephalostatins 18 and 19.

Continued investigation of murine leukemia (P-388) active fractions from the African marine worm Cephalodiscus gilchristi has resulted in the discovery of cephalostatins 18 (1b) and 19 (1c). The structures were determined by interpretation of their highfield (500 MHz) 1H, 13C, and 2D NMR and HRMS. Both of these new methoxy steroidal alkaloids exhibited strong activity against the murine P-388 lymphocytic leukemia cell line (ED50 ca. 10(-3) microg/mL), a mini panel of human cancer cell lines (GI50 <10(-3) microg/mL), and the U.S. National Cancer Institute's 60 human cancer cell line panel (mean panel GI50 ca. 10(-9) M).

Overlapping phenotypes of multidrug resistance among panels of human cancer‐cell lines

In addition to P-glycoprotein (Pgp), 2 proteins related to multidrug resistance (MDR) have recently been described. The Multidrug-Resistance-associated protein (MRP) is one of the ATP-binding-cassette (ABC) transporters. The Lung-Resistance Protein (LRP) is the major component of human vaults, which are newly described cellular organelles and thought to mediate intracellular transport processes. Using immunocytochemical methods, we have examined the expression of MRP and LRP among panels of human cancer-cell lines not selected for drug resistance which have been previously characterized for expression of Pgp, and in vitro response to a variety of anti-cancer drugs. Expression of MRP and LRP was observed in 47/55 (87%) and 46/59 (78%) cell lines, respectively. Statistically significant correlations were observed between expression of each of these 3 proteins and in vitro sensitivity to at least one drug classically associated with MDR. LRP showed the greatest individual predictive value, which also applied to several non-classical MDR drugs. Co-expression of 2–3 MDR-related proteins was observed in 64% of the lines and was, in general, associated with high relative levels of drug resistance. Previously identified “classic” MDR lines as well as “pan-resistant” lines concurrently expressed all 3 MDR-related proteins. Some highly drug-resistant cell lines without detectable MDRI/Pgp were found to express relatively high levels of MRP and LRP. The high prevalence of MRP and LRP expression observed in this large set of cell lines, which have not been subjected to laboratory drug selection, suggests that MDR mechanisms associated with these proteins may be widespread in human malignancies. Moreover, the overlapping of these more recently recognized MDR phenotypes with Pgp-type MDR results in a complex phenotype, the understanding of which may be of importance in the development of new drugs and design of clinical treatment protocols, particularly those seeking to employ strategies to reverse the MDR phenotype. © 1996 Wiley-Liss, Inc.

Antitumor Agents, 119. Kansuiphorins A and B, Two Novel Antileukemic Diterpene Esters from Euphorbia kansui

The extract of the roots of Euphorbia kansui, which has been widely used in Chinese folk medicine for the treatment of cancer, demonstrated antileukemic activity against the P-388 lymphocytic leukemia in mice. Bioassay-directed fractionation of the active extract led to the isolation and characterization of two novel antileukemic diterpene esters, kansuiphorin A [1] [13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-dodecanoate- 20- hexadecanoate] and kansuiphorin B [2] [6,7-epoxy-13-hydroxyingenol-3-(2,3-dimethylbutanoate)-13-do decanoate-20- hexadecanoate], whose structures were established from spectral evidence and chemical transformation. Kansuiphorins A and B demonstrated potent antileukemic activity with T/C greater than or equal to 176 and 177% at 0.1 and 0.5 mg/kg, respectively. The selectivity of kansuiphorin A, which inhibits the growth of particular cell types within the disease-oriented human cancer cell line panels, is discussed.

The Cytotoxic Principles ofPseudolarix kaempferi: Pseudolaric Acid-A and -B and Related Derivatives1

Pseudolaric acid-A and -B, the novel diterpene acids isolated from Pseudolarix kaempferi, and their related derivatives have been tested for cytotoxicity against KB, A-549, HCT-8, P-388, and L-1210 tumor cells. The results showed that pseudolaric acid-A and -B demonstrated potent cytotoxicity. The selectivity of pseudolaric acid-A and -B which inhibit the growth of particular cell types within the disease-oriented human cancer cell line panels is discussed.

NIH New Drug Program

Over the last 3 decades the National Cancer Institute has evaluated a variety of models for anticancer drug screening. Predominant among these have been the in vivo murine leukemias L1210 and P388. Currently, the NCI principal screening experiment incorporates the P388 model as a high capacity (10,000 compounds/year) prescreen; second tier testing is performed on a relatively limited number (200 compounds/year) of P388 “actives” against a “tumor panel” which presently consists of 4 in vivo tumor models including the L1210 murine leukemia, the B16 mouse melanoma, the M5076 murine sarcoma and the human MX-1 mammary xenograft. The tumor panel experiment was initiated in 1976 to explore whether the P388 + tumor panel would detect new agents that would have been missed by L1210 alone, and whether ultimately such an approach might facilitate the discovery of new agents effective against tumor types which have thus far proved highly refractory to chemotherapy. Current analyses of the tumor panel experiment indicate that, thus far, this predominantly “compound-oriented” approach has identified some new agents with apparent clinical activity, however mostly within the leukemia/lymphoma family. Unfortunately, none of the current models employed has identified new drug candidates with particularly promising activity in any of the major human solid tumors including lung cancer, colorectal cancer, breast cancer, prostatic cancer and others. 1 Venditti JM Wesley RA Plowman J Current NCI pre-clinical antitumor screening in vivo. Results of tumor panel screening, 1976-1982, and future directions. in: Garattini S Goldin A Hawking F Advances in pharmacology and chemotherapy, 20. Academic Press, Orlando, Florida1984: 1-20 Google Scholar , 2 Boyd MR. NCI drug discovery and development. Proceedings of the General Motors Cancer Research Foundation Conference on “Cancer Therapy: where Do We Go From Here,” Jackson Hole, Wyoming: September 14-15, 1984 Google Scholar , 3 Proceedings of the Workshop on Disease-Oriented Antitumor Drug Discovery and Development. National Institutes of Health, Bethesda, MarylandJanuary 9-10, 1985: 1-273 Google Scholar , 4 NCI planning to switch drug development emphasis from compound to human cancer-oriented stratgegy. The Cancer Letter. 1984; 10 (October 26): 1-3 Google Scholar , 5 DCT board approves new screening program, natural product concepts. The Cancer Letter. 1985; 11 (March 1): 4-8 Google Scholar Presently, therefore, the NCI is developing an alternative “disease-oriented” screening experiment. 2 Boyd MR. NCI drug discovery and development. Proceedings of the General Motors Cancer Research Foundation Conference on “Cancer Therapy: where Do We Go From Here,” Jackson Hole, Wyoming: September 14-15, 1984 Google Scholar , 3 Proceedings of the Workshop on Disease-Oriented Antitumor Drug Discovery and Development. National Institutes of Health, Bethesda, MarylandJanuary 9-10, 1985: 1-273 Google Scholar , 4 NCI planning to switch drug development emphasis from compound to human cancer-oriented stratgegy. The Cancer Letter. 1984; 10 (October 26): 1-3 Google Scholar , 5 DCT board approves new screening program, natural product concepts. The Cancer Letter. 1985; 11 (March 1): 4-8 Google Scholar The new screening approach will incorporate a variety of representative in vitro and in vivo models representing specific target disease types. The first phase of the new screening experiment is designated as the NCI Lung Cancer Drug Discovery Project (LCDDP). For the LCDDP, the “prescreen” will consist of a well-defined, diverse and representative human lung cancer cell line panel (20-30 lines) against which substances will be tested initially using in vitro assays. Non-cancer cell lines as well as selected murine tumor cell lines (P388, L1210) and other human tumor cell lines will be included in the prescreening panel to provide comparative data and to facilitate the assessment of tumor type selectivity.