Solid cancer cell lines

The synthesis of novel quinoxaline derivatives was key in the study of inhibitors of Pirn kinases. This structure-activity relationship (SAR) study found several promising molecules that demonstrated antiproliferative properties against solid cancer cell lines (PAl, PC3, and DU145). The synthesis of these compounds relied on the previously optimized condensation of diamines with a-halogenated carbonyls followed by oxidation to provide the aromatic bicycle. ... 

The antineoplastic activity of vanadium compounds has been studied for some time. In 1979, the metalocene compound, biscyclopentadienyldichloro-Vanadium(IV), (C5H5)VCI2, was found to have antitumor activity [161], The compound inhibited the growth of various cancer cell lines and the growth of solid tumors in vivo. Vanadium(V) peroxocomplexes with known insulin-mimetic activity were shown to have antitumor activity against murine leukemia cells at that time. Vanadocene compounds are now known to induce apoptosis in cell lines. The apoptotic signal... 

Johvet, J., Lafieniere, R.G., and Cass, C.E. (2001) Mechanisms of uptake and resistance to troxacitabine, a novel deoxycytidine nucleoside analogue, in human leukemic and solid tumor cell lines. Cancer Research, 61 (19), 7217-7224. 

Triptolide has been shown to induce apoptosis of several human cancer cell lines grown in culture and to inhibit tumor development in a murine breast cancer model " but has shown toxicity at high doses. The 14-succinyl sodium salt of triptolide (34), known as PG490-88, suppresses tumor growth without toxicity and has entered Phase I clinical trials the data is summarized as follows Our results suggest a potential role of PG490-88 alone and in combination with chemotherapy as a novel antineoplastic regimen for the treatment of patients with solid tumors. ... 

The natural product wortmannin proved unsuitable for clinical use due to poor stability and general toxicity. Oncothyreon has advanced a derivative of wortmannin, PX-866 ((39), Figure 6.16), to Phase I clinical trials in patients with advanced solid tumors. The compound displays selectivity for the PI3K-x, -5, and -y isoforms relative to PI3K-(i and mTOR.74 A comparison of the behavior of PX-866 and wortmannin in human cancer cell lines was performed in this study, PX-866 was found to limit cancer cell motility in three-dimensional spheroid cultures at subnanomolar levels.75... 

Maurer, B.J., Melton, L., Billups, C., Cabot, M.C., and Reynolds, C.P. Synergistic cytotoxicity in solid tumor cell lines between N-(4-hydroxyphenyl)retinamide and modulators of ceramide metabolism. J Natl Cancer Inst, 92, 2000, 1897-1909. 

The control of inverse transition temperatures by sequence manipulation and biocompatibility of ELPs make them useful polymers for drug delivery. Cultured cancer cells and solid tumors in animal models uptake fluorescently labeled ELPs in a thermally responsive manner (48,49). Two major limitations in cancer therapy have been the inability of therapeutic molecules to cross the cell membrane and the target-specificity of the compounds. To overcome these limitations cell-penetrating, peptides (CPP) have been fused with ELPs (CPP-ELP) to develop thermally responsive therapeutics with the ability to translocate the cell membrane (Figure 3B). CPPs can assist in the transportation of hydrophilic compounds (small molecules, oglionucleotides and peptides) across the cell membrane (50). Fusing ELPs to a variety of CPPs have revealed that the peptide sequence of penetratin demonstrates the most efficient cellular uptake (51). Further, these CPP-ELPs have been fused to a c-Myc inhibitory peptide known to target and inhibit cancer. As proof of principle, these fusion proteins inhibits proliferation of cultured cancer cell lines in a thermally responsive manner (52). 

In 1991, the effects of triptolide (79) on the colony formation of breast cancer (MCFG-7 and BT-20), stomach cancer (Ml -45, MKN-7, and KATO-III), and promyelocytic leukemia (HL-60) cell lines, were reported [172]. The magnitudes of the inhibitory effect of triptolide on both breast and stomach cancer cell lines were similar to that of the leukemia cell line HL-60 (IC50 0.504-1.22 ig/1). The results obtained suggested that triptolide might have a potential therapeutic effect on some types of solid tumors, e.g., breast and stomach cancers. 

Caco-2 is a human intestinal cancer cell line that can form a well-differentiated monolayer on a solid support that mimics the human intestinal epithelium, where most drug absorption occurs. This makes it useful in a cellular equivalent of a PAMPA sandwich that s more... 

The second-generation of HDAC inhibitors have shown improved potency over vorinostat, and these include the indole-based dacinostat and panobinostat (http // www.novartisoncology.com/research-innovation/pipelineJsp) [16] originated from Novartis. Both agents inhibit HDAC and the proliferation of cancer cell lines at low nanomolar concentrations and have demonstrated efficacy in a number of solid tumor xenografic models. Dacinostat was advanced to phase I clinical trials in 2002 but discontinued in 2005. Panobinostat is currently in phase 11/111 studies for the treatment of hematological cancers. 

Several reviews have highlighted the benefit of targeting tumor hypoxia, generally, and the HIF-1 pathway, specifically, in treating solid tumors [13, 77, 189]. Therefore, I will focus on those pathways and inhibitors that have been tested in vitro in breast cancer cell lines, that have been tested for efficacy in animal models of cancer, or that have been used successfully in clinical trials to treat solid tumors. 

Shi, Y Xiang, R. Horvath, C. Wilkins, J.A. Quantitative analysis of membrane proteins from breast cancer cell lines and MCF7 using multistep solid phase mass tagging and 2D LC/MS. J. Proteome Res. 2005, 4, 1427-1433. 

A number of studies reported in the literature reveal wide array of polyphenol compounds derived from common dietary sources and medicinal plants wield antitumor effects through the suppression of NF-kB DNA binding activity in myeloid, lymphoid, and several solid tumor cell lines derived from prostate, breast, head and neck, and pancreatic cancer cells resulting in the inhibition of downstream target genes that are critical for the establishment of aggressive cancers. This ultimately leads to the inhibition of cell growth and induction of apoptotic cell death [118-120]. 

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