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M López-Lázaro

Publications and source records attributed to M López-Lázaro.

10 recordsLinked to original sources
PubMed2002

Flavonoids as DNA topoisomerase I poisons.

The therapeutic anticancer potential of flavonoids shown by recent research needs a greater understanding of these compounds. They are antioxidants and antimutagenic agents that can inhibit tumor promotion and transformation and can modify the activity of a large number of mammalian enzyme systems, such as human DNA-topoisomerases. Poisons of topoisomerases generate toxic DNA damage by stabilization of the covalent DNA-topoisomerase cleavage complex and some of them have therapeutic efficacy in human cancer. The present investigation has assayed ten flavonoids, isolated in our laboratory, as topoisomerase I poisons obtaining myricetin and myricetin-3-galactoside as two new topoiosomerase I poisons. These two flavonoids, and the plant extract from which they were isolated, were assayed for cytotoxic activity against three human cancer cell lines using the SRB assay. Taking into account our previous research, structural requisites implicated in the topoisomerase poisoning are discussed.

Antineoplastic Agents↗
PubMed2002

Flavonoids as anticancer agents: structure-activity relationship study.

The protection against some forms of cancer provided by many common foods has been observed in multiple epidemiological studies. Non-nutritive dietary compounds, such as flavonoids, have been considered as the responsible agents for such observations and since then, much research activity has been done about their potential anticancer effect. As a result, these compounds have been shown to regulate proliferation and cell death pathways leading to cancer. Thus, flavonoids such as the synthetic flavone, flavopiridol; the soy isoflavonoid, genistein; the tea catechin epigallocatechin gallate; or the common dietary flavonol, quercetin, are emerging as prospective anticancer drug candidates and some of them have already entered in clinical trials. In view of the therapeutic potential of flavonoids, many researchers have tried to elucidate possible structure-activity relationships that might lead to new drug discovery. However, and possibly due to the information being very scattered, there is very little understanding about a possible relationship between the flavonoid structure and their anticancer activity. Besides their therapeutic potential, since lots of flavonoids are present in our diet, a greater understanding of their anticancer properties might also modify our dietary habits in order to attack cancer with an effective weapon, prevention. This paper seeks to show, in a brief but comprehensive way, the anticancer properties of flavonoids. Through an understanding of the cancer process and its treatment, flavonoids are studied as possible useful compounds in cancer prevention and cancer therapy. Furthermore, this review attempts to compile and discuss the literature studying structure-activity relationships, in order to show structural requirements implicated in the anticancer activity of flavonoids, which might help to rationalize their development as antitumor agents.

Animals↗
PubMed2001

A cytotoxic diarylheptanoid from Viscum cruciatum.

A diarylheptanoid, 1,7-di-(3',4'-dihydroxyphenyl)-4-hepten-3-one, hirsutanone, has been isolated from the methanolic extract of the aerial parts of Viscum cruciatum (Viscaceae) and characterized by spectroscopic methods and chemical transformations. This compound showed cytotoxic activity against melanoma (UACC-62), renal (TK-10) and breast (MCF-7) cancer cell lines.

Antineoplastic Agents, Phytogenic↗
PubMed2001

Assessment of genotoxic damage by the comet assay in white storks (Ciconia ciconia) after the Doñana Ecological Disaster.

Single cell gel electrophoresis, the so-called "Comet" assay, was performed as a genotoxicity test in white storks sampled in an area heavily contaminated after the ecological disaster in south western Spain. This disaster occurred as a consequence of a massive toxic spillage of acid waste rich in heavy metals that impacted on the Doñana National Park. The importance of this protected area as a breeding and wintering site for many endangered bird species makes this analysis of DNA damage of special interest. Our results clearly show that white storks born in the contaminated area 1 year after the toxic spill bear a high burden of genetic damage as compared with control individuals. The possible implications for future survival as well as reproductive rate are discussed.

Animals↗
PubMed2001

DNA damage in birds after the mining waste spill in southwestern Spain: a Comet assay evaluation.

In April 1998, an ecological disaster resulting from a massive toxic spill of mining acid waste rich in heavy metals posed a serious threat to the Doñana National Park in southwestern Spain. This especially important protected area is the nesting and breeding site for many endangered bird species; white storks (Ciconia ciconia) and black kites (Milvus migrans) are considered the more representative. The suitability of the Comet assay as a biomarker for genotoxic analysis in environmental biomonitoring has been recently validated in studies using different sentinel organisms such as fish, amphibians, rodents, or mollusks. Birds preying on a variety of invertebrate and vertebrate species in the marshlands are appropriate for evaluating the potential deleterious effects of the toxic spill on wildlife of the Dofiana area. Our study on wetland birds high on the aquatic trophic chain sampled within a few months after the toxic spill in the area around Doñana National Park has shown the accumulation of heavy metals. Fourteen months after the mine waste spill, blood samples from white storks and kites collected in the neighborhood of the park and from control birds at reference areas for comparison were examined by fluorescence image analysis after lymphocyte isolation, and by subsequent alkaline single-cell gel (SCG) electrophoresis, known as the Comet assay. Our results indicate that the exposed birds had a significantly increased level of genotoxic damage compared with control animals from noncontaminated locations.

Accidents, Occupational↗
PubMed2000

Retamatrioside, a new flavonol triglycoside from Retama sphaerocarpa.

A new flavonol triglycoside, retamatrioside (1), has been isolated from the aerial parts of Retama sphaerocarpa. The structure of 1 has been determined as rhamnazin 3-O-beta-D-glucopyranosyl-(1-->5)-[beta-D-apiofuranosyl(1-->2)]-al pha -L-arabinofuranoside, using spectroscopic methods.

Carbohydrate Sequence↗
PubMedDate not supplied

Cytotoxic activity of flavonoids and extracts from Retama sphaerocarpa Boissier.

Seven flavonoids isolated from chloroform, ethyl acetate and butanol extracts, obtained from the aerial parts of Retama sphaerocarpa, have been assessed for cytotoxic activity against three human cancer cell lines: TK-10 (renal adenocarcinoma), MCF-7 (breast adenocarcinoma) and UACC-62 (melanoma), using the SRB assay. All of them, extracts and flavonoids, were actives in, at least, one of the three cell lines at the recommended National Cancer Institute doses. They produce a dose-dependent inhibition of cell growth at concentrations in the 10(-6)-10(-4) M and 25-250 microg/ml range for the flavonoids and extracts respectively, being the flavonol rhamnazin the most cytotoxic.

Adenocarcinoma↗
PubMedDate not supplied

Two new flavonol glycosides as DNA topoisomerase I poisons.

Flavonoids are secondary plant metabolites whose anticancer properties are actually being studied from an epidemiological and pharmacological point of view. They are believed to be implicated in the lower risk of some forms of cancer observed in Asian countries, due to their capacity to control cell proliferation, to act on certain regulatory enzymes as protein kinases or topoisomerases. Based on these precedents, three flavonols isolated from a cytotoxic butanol extract from Retama sphaerocarpa Boissier have been assessed to study their topoisomerase I and II activity. Two new rhamnazin glycosides were found to have the ability to stabilize the cleavage complex human DNA topoisomerase I at concentrations in the 100-250 microM range, acting as topoisomersase I poisons.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Cytotoxic compounds from Annonaceus species as DNA topoisomerase I poisons.

BACKGROUND: In the search for cytotoxic natural products as DNA topoisomerase poisons, we have assessed six annonaceus compounds (the acetogenins annonacin and rolliniastatin-1, the styryl-lactones etharversin and altholactone and the alkaloids thaligrisine and cepharanone-B) for cytotoxic activity against three human cancer cell lines and then we evaluated these compounds as DNA topoisomerase poisons. MATERIALS AND METHODS: The cytotoxicity parameters were determined following protocols established by the National Cancer Institute (NCI) using the SRB assay. In the topoisomerase assay, the supercoiled DNA produces open circle forms that are stabilised in the presence of DNA topoisomerase poisons and can be detected after a denaturation step by proteinase K-SDS. RESULTS: The six compounds showed cytotoxic activity, with cepharanone B being the most cytotoxic one, even more than the antineoplastic agent etoposide on two cancer cell lines, although it is the only one that does not act as a DNA topoisomerase poison. CONCLUSION: These results could justify the traditional use of the studied annonaceus species and topoisomerase-mediated DNA damage might be a possible mechanism by which five of these compounds exert their cytotoxicity.

Annonaceae↗