Cancer cell lines inhibition activity

The present work seeks to compile information about the cancer cell lines inhibited by different groups of natural and synthetic flavonoids reported in the literature and try to find and discuss structural requirements implicated in the activity to obtain a working hypothesis to help to rationalize the development of flavonoids as antitumor compounds. 

A series of anthraquinones has been chemically synthethized and the influences of structural features, such as the different functionalities in the nucleus have been studied in relation to cytotoxicity toward neoplastic cells. l,3-dihydroxy-9,10-anthraquinone synthetic derivatives were tested in vitro for inhibition against several different human cancer cell lines. Structure-activity analysis indicates that epoxidation of the hydroxyanthraquinone increased cytotoxicity against tumor cells, but ring-opening of the epoxide... 

Krystal, G.W. et al., Lck associates with and is activated by Kit in a small cell lung cancer cell line inhibition of SCF-mediated growth by the Sre family kinase inhibitor PPl, Cancer Res., 58,4660,1998. 

The RXR-RXR antagonist LDG100754 and RAR-selective TTNPB activated RXR-RAR heterodimers on DR-2 and DR-5 RAREs, whereas LDG100268 did not however, only TTNPB dissociated the corepressor SMRT from the RXR-RAR complex [36]. The synergy between RXR-selective retinoids and RAR-selective retinoids was ably demonstrated by Wu et al. [105]. RXR-selective SRI 1345 at 1.0 pM, which only inhibited MDA-MB-231 breast cancer cell growth by less than 5%, enhanced the inhibitory activity of RAR-selective SRI 1365 from below 5% to 55%. In the ZR-75-1 human breast cancer cell line, inhibition by SRI 1365 rose from 40% to 70%, after addition of SRI 1345, which alone was inactive. 

Barbieri and coworkers have studied the antiproliferative activity and interactions of cell-cycle-related proteins utilizing the organotin compoimd containing a quinolizidine derivative. The particular compoimd studied was triethyltin lupinylsulfide hydrochloride (5). In early tests this compound was found to show good cancer cell line inhibition, so more extensive studies were undertaken. 

Table 7.3 shows the concentrations of 1-5 that result in 50% growth inhibition (GI50) of five human cancer cell lines. Inspection of these data reveals that cytostatic activity of 1 and 3-5 depends on the thermodynamic favorability of the quinone methide species compared to the corresponding keto form. The most cytostatic prekinamycins 1 and 5 are associated with the thermodynamically stable quinone methides. In contrast, the inactive prekinamycins 3 and 4 are associated with thermodynamically stable keto tautomers. The exception is prekinamycin 2, which is cytostatic and possesses a relatively stable keto tautomer 3 compared to its quinone methide. Although the AE value for quinone methide tautomerization can predict cytostatic properties, prekinamycin 2 shows that there must be other factors determining biological activity. 

The plant is known to contain chelerythrine chloride, which inhibits the aggregation of rabbit platelet in vitro via inhibition on thromboxane formation and phosphoinosi-tides breakdown (30). Chelerythrine, which occurs in members of the family Papaver-aceae, has been reported to inhibit the enzymatic activity of protein kinase C and to exert cell-growth inhibitory effect via the induction of apoptosis in numerous cancer cell lines (31,32). What is the topoisomerase activity of chelerythrine ... 

In China, the plant affords a tonic remedy particularly recommended for chest complaints. Indonesians use the leaves medicinally because they are strongly aromatic. The pharmacological potentials of this plant are, to date, unknown. Note that 6 3-hydroxy-3-oxo-lup-20(29)-en-28-oic acid and 3,1 l-dioxoolean-12-en-28-oic acid from the stem bark of Liquidambar styraciflua, as well as 25-acetoxy-3a-hydroxyolean-12-en-28-oic acid, inhibited the growth of several cancer cell lines (43). What is the activity of 25-acetoxy-3a-hydroxyolean-12-en-28-oic acid against topoisomerase ... 

Another peculiarity of the study is that the use of a biological system has allowed the authors to hypothesize a possible mechanism of action of the leachate as a mixture, hypothesis that could have been drafted on the basis of the only knowledge derived by chemical analysis. Researchers suggest that leachate inhibits cell proliferation at low doses probably inducing a reversible cell cycle arrest that becomes irreversible at high doses, probably due to leachate-induced oxidative stress. This activity is mainly due to the chemical compounds extracted in the aqueous phase. Similar effects were noticed by previous investigations on other human cells (human peripheral blood lymphocytes and a human breast cancer cell line, MCF-7) [31, 32], supporting the hypothesis that cells that survive the initial insult from leachate constituents maintains the potential to proliferate until the effects on cell metabolism lead to death. 

---