Miguel López-Lázaro

Universidad de Sevilla | US · Pharmacology

Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy ha...

Abstract: Recent research shows that listening to music and making music can promote health-related quality of life in healthy populations and people with a variety of conditions and diseases such as stress, anxiety, depression, Alzheimer disease and cancer. In active music therapy, patients are asked to make music, e.g., by singing, playing instru...

Every year, cancer kills millions of people around the world. Finding more selective anticancer agents is essential to improve the low survival rates of patients with metastatic cancers. Since the research of natural products is a valuable approach to the discovery of new compounds and the Iberian flora offers a rich source of unstudied plants, we...

Cancer cells cannot proliferate and survive unless they obtain sufficient levels of the 20 proteinogenic amino acids (AAs). Unlike normal cells, cancer cells have genetic and metabolic alterations that may limit their capacity to obtain adequate levels of the 20 AAs in challenging metabolic environments. However, since normal diets provide all AAs...

Cancer cells cannot proliferate and survive unless they obtain sufficient levels of the 20 proteinogenic amino acids (AAs). Unlike normal cells, cancer cells have genetic and metabolic alterations that may limit their capacity to obtain adequate levels of the 20 AAs under challenging metabolic environments. However, since normal diets provide all A...

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show for the first time that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acid...

Sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricted die...

The sulfur-containing amino acids methionine (Met), cysteine (Cys) and taurine (Tau) are common dietary constituents with important cellular roles. Met restriction is already known to exert in vivo anticancer activity. However, since Met is a precursor of Cys, and Cys produces Tau, the role of Cys and Tau in the anticancer activity of Met-restricte...

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids...

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated witho...

New therapies are needed to improve the low survival rates of patients with metastatic colon cancer. Evidence suggests that amino acid (AA) restriction can be used to target the altered metabolism of cancer cells. In this work, we evaluated the therapeutic potential of selective AA restriction in colon cancer. After observing anticancer activity in...

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated witho...

Complexes Na3[Ag(NHCR)2], 2a-e and 2b’-c’, where NHCR is a N-heterocyclic carbene of the 2,2′-(1H-2λ³,3λ⁴-imidazole-1,3-diyl)dicarboxylate type, were prepared by treatment of compounds HLR, 1a-e and 1b’-c’ (2-(1-(carboxyalkyl)-1H-imidazol-3-ium-3-yl)carboxylate), with silver oxide in the presence of aqueous sodium hydroxide. They were characterized...

Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10% morphine and 2% codeine. It is commonly used to prepare opium tinctures for people with chronic diarrhea. Morphine and related opioids are powerful but highly addictive analgesics;...

Liposomes (Lip) are useful nanocarriers for drug delivery and cancer nanomedicine because of their ability to efficiently encapsulate drugs with different physical and chemical properties. The pH gradient between normal and tumoral tissues, and their rapid metabolism that induces hyperthermia encourage the development of pH- and thermo-sensitive Li...

We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[N-(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore the possible mechanisms involved in...

This preprint is now published (open access) in the journal Current Pharmaceutical Design https://www.eurekaselect.com/article/124229 Opium is defined as the air-dried latex obtained by incision from the unripe capsules of Papaver somniferum L. Opium is a complex mixture that contains approximately 10% morphine and 2% codeine. It is commonly use...

Finding cytotoxic drugs with a high selectivity towards cancer cells is crucial to improve the low survival rates of patients diagnosed with metastatic cancers. Since plants are an important source of anticancer drugs, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity on lung...

Stimulus-responsive liposomes (L) for triggering drug release to the target site are particularly useful in cancer therapy. This research was focused on the evaluation of the effects of cholesterol levels in the performance of gold nanoparticles (AuNPs)-functionalized L for controlled doxorubicin (D) delivery. Their interfacial and morphological pr...

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1–8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL...

Carbohydrate-lectin interactions are involved in a number of relevant biological events including fertilization, immune response, cell adhesion, tumour cell metastasis, and pathogens infection. Lectins are also tissue specific, making carbohydrates...

The Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient cells are unable to recover from transcription-blocking DNA lesions. 5-Aza-2'-deoxycytidine (5-azadC) is a nucleoside analogu...

Objectives To provide mechanistic evidence for the epidemiological link between long-term use of alcohol-containing mouthwashes and oral cancer. Material and methods Human epithelial keratinocytes were exposed for 30 s to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT as...

In our continuous search for selective anticancer treatments, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity against lung cancer cells and lung normal cells. Active extracts were also tested against 11 cell lines from other tissues. An extract from the leaves of Tetraclinis...

Since plants are an important source of anticancer drugs, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 plants collected in Grazalema Natural Park, an area in the South of Spain of high plant diversity and endemism. Using lung cancer cells (A549) and lung non-malignant cells (MRC-5), we found that s...

We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[N-(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore possible mechanisms involved in the...

Several clinically useful anticancer drugs selectively kill cancer cells by inducing DNA damage; the genomic instability and DNA repair defects of cancer cells make them more vulnerable than normal cells to the cytotoxicity of DNA-damaging agents. Because epoxide-containing compounds can induce DNA damage, we have used the MTT assay to evaluate the...

Objective: To provide mechanistic evidence for the epidemiological link between long-term use of alcohol containing mouthwashes and oral cancer.Methods: Human epithelial keratinocytes were exposed for 30 seconds to concentrations of ethanol commonly present in mouthwashes. After a recovery period, cell viability was assessed with the MTT assay.Resu...

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and lung cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic conce...

Although several plant-derived drug groups (vinca alkaloids, taxanes, podophyllotoxin derivatives and camptothecins) continue to be widely used in cancer therapy, the anticancer potential of the Plant Kingdom remains largely unexplored. In this work, we have carried out a random screening for selective anticancer activity of 57 extracts from 45 pla...

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of un...

Alcohol consumption is a known risk factor for cancer. Almost 6% of all cancers worldwide are attributable to alcohol use. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the mutagenic metabolite of ethanol (acetaldehyde)...

Recent evidence indicates that the risk of being diagnosed with cancer in a tissue is strongly correlated (0.80) with the number of stem cell divisions accumulated by the tissue. Since cell division can generate random mutations during DNA replication, this correlation has been used to propose that cancer is largely caused by the accumulation of un...

All cancer registries constantly show striking differences in cancer incidence by age and among tissues. For example, lung cancer is diagnosed hundreds of times more often at age 70 than at age 20, and this cancer in nonsmokers occurs thousands of times more frequently than heart cancer in smokers. An analysis of these differences using basic conce...

Almost 6% of cancers worldwide are attributable to alcohol consumption. Approximately half of them occur in tissues highly exposed to ethanol, such as the oral cavity, pharynx, upper larynx and esophagus. However, since ethanol is not mutagenic and the carcinogenic metabolite of ethanol (acetaldehyde) is mainly produced in the liver, it is unclear...

Zebularine is a second-generation, highly stable hydrophilic inhibitor of DNA methylation with oral bioavailability that preferentially target cancer cells. It acts primarily as a trap for DNA methyl transferases (DNMTs) protein by forming covalent complexes between DNMT protein and zebularine-substrate DNA. It’s well documented that replication-bl...

A library of 5-arylthiosubstituted 2-amino-4,6-diaryl-3-cyano-4H-pyrans has been synthesized as a new family of non-peptide NK1 receptor ligands by a one-pot cascade process. Their biological effects via interaction with the NK1 receptor were experimentally determined as percentage of inhibition (for antagonists) and percentage of activation (for a...

Preprint at: https://www.preprints.org/manuscript/201608.0158/v1/download Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. However, since ethanol is not muta...

Extremely low-frequency electromagnetic fields (ELF-EMFs) are non-ionizing radiations typically emitted by power lines, electrical wiring and electrical appliances. Epidemiological studies have repeatedly shown a positive association between ELF-EMFs and childhood leukemia. Exposures greater than 0.3-0.4 µT increase the risk by approximately 1.5-2...

Epidemiological data indicate that 5.8% of cancer deaths world-wide are attributable to alcohol consumption. The risk of cancer is higher in tissues in closest contact on ingestion of alcohol, such as the oral cavity, pharynx and esophagus. The risk of these cancers is increased even in people who have only one alcoholic drink per day. However, sin...

Tobacco use, most people would say. Smoking tobacco increases the risk of developing many typesof cancer and is responsible for approximately one-third of all cancer deaths. The associationbetween tobacco use and lung cancer is well known; lung cancer occurs about 20 times more oftenin heavy smokers than in nonsmokers [1]. However, many lung cancer...

Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in chil...

Metastasis will continue to be an incurable disease for most patients until we develop highly selective anticancer therapies. The development of these therapies requires finding and exploiting major differences between cancer cells and normal cells. Although the sum of the many DNA alterations of cancer cells makes up such a major difference, there...

Cancer is, in essence, a stem cell disease. The main biological cause of cancer is that stem cells acquire DNA alterations during cell division. The more stem cell divisions a tissue accumulates over a lifetime, the higher is the risk of cancer in that tissue. This explains why cancer is diagnosed millions of times more often in some tissues than i...

Cancers of unknown primary site are metastatic cancers for which primary tumors are not found after detailed investigations. In many cases, the site of origin is not identified even on postmortem examination. These cancers are the fourth most common cause of cancer death. The biological events involved in the development of this type of cancers rem...

Nanoplatforms can optimize the efficacy and safety of chemotherapy, and thus cancer therapy. However, new approaches are encouraged in developing new nanomedicines against malignant cells. In this work, a reproducible methodology is described to prepare Δ(9)-tetrahidrocannabinol (Δ(9)-THC)-loaded poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles...

Current approaches to assessing preclinical anticancer activity do not reliably predict drug efficacy in cancer patients. Most of the compounds that show remarkable anticancer effects in preclinical models actually fail when tested in clinical trials. We blame these failures on the complexity of the disease and on the limitations of the preclinical...

Wang and colleagues ([1][1]) recently reported that the cardiac glycoside bufalin was a potent inhibitor of the steroid receptor coactivators SRC-3 and SRC-1. Because these coactivators have been implicated in cancer progression, the authors investigated whether bufalin could also block cancer cell

Cancer patients need better anticancer drugs, and medicinal chemistry can play a critical role in the discovery of these drugs. For an efficient drug discovery process, chemists working on the synthesis of potential anticancer agents need to use reliable screening methods. These methods should not only detect the compounds with the highest therapeu...

This work reports the antiproliferative activity of seco-oxacassanes 1–3, isolated from Acacia schaffneri, against human colon (HT-29), lung (A-549), and melanoma (UACC-62) cancer cell lines, as well as against their non-malignant counterparts CCD-841 CoN, MRC-5, and VH-10, respectively, using the sulforhodamine B test. While compounds 1 and 3 were...

Reported is an enantiodivergent approach for the synthesis of both enantiomers of sulforaphane (SFN) homologues with different chain lengths between the sulfinyl sulfur and the isothiocyanate groups and different substituents on the sulfinyl sulfur. The homologues were designed in order to unravel the effect of all the diversity elements included i...

Decitabine (5-aza-2′-deoxycytidine, 5-azadC) is used in the treatment of Myelodysplatic syndrome (MDS) and Acute Myeloid Leukemia (AML). Its mechanism of action is thought to involve reactivation of genes implicated in differentiation and transformation, as well as induction of DNA damage by trapping DNA methyltranferases (DNMT) to DNA. We demonstr...

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 flav...

Tumor cells often have defects in DNA repair pathways that make them vulnerable to specific DNA-damaging anticancer agents. The identification of DNA repair defects in tumor cells and the evaluation of their influence on the cytotoxicity of anticancer drugs are active areas of scientific investigation that may help rationalize and improve cancer ch...

Cardiac glycosides, also known as cardiotonic steroids, are a group of natural products that share a steroid-like structure with an unsaturated lactone ring and the ability to induce cardiotonic effects mediated by a selective inhibition of the Na(+)/K(+)-ATPase. Cardiac glycosides have been used for many years in the treatment of cardiac congestio...

Background: The low efficacy of cancer therapy for the treatment of patients with advanced disease makes the development of new anticancer agents necessary. Because natural products are a significant source of anticancer drugs, it is important to explore cytotoxic activity of novel compounds from natural origin. Purpose: The aim of this work is...

The leaves of Corema album (Ericaceae), an endemic shrub which grows in Atlantic coastal areas of the Iberian Peninsula, are rich in flavonoids and other secondary metabolites. Silica gel column chromatography of the ethyl acetate extract from dried leaves was performed and a flavonic active fraction was obtained. The cytotoxic activity of this fra...

A series of new aziridines β-D-galactopyranoside derivatives were synthesized from alkenyl β-D-galactopyranosides employing Sharpless conditions. The structures of the compounds were established by (1)H NMR, (13)C NMR, MS, HRMS and elemental analysis. The stereoselectivity of the reaction and the structural requirements of the alkenyl precursor for...

During our search for cytotoxic compounds from Andalusian vascular plants, the ethyl acetate extract from the leaves of Corema album (L.) D. Don (Ericaceae) was selected for its cytotoxic activity against the HT-29 human colon adenocarcinoma cell line. Two dihydrochalcones, 2',4'-dihydroxydihydrochalcone (1) and 2'-methoxy-4'-hydroxydihydrochalcone...

Sideritis perezlarae is a plant widely used in folk medicine in the South of Andalusia (Cádiz, Spain). In this work, a phytochemical analysis has led to the isolation and identification of the flavonoid 7-O- β -glucosyl-luteolin from a methanol extract. The total phenol content estimated by Folin-Ciocalteau assay and expressed as gallic acid equiva...

Recent evidence suggests that cardiac glycosides might be used for the treatment of cancer. The ornamental shrub Nerium oleander has been used in traditional medicine for treating several disorders including cancer, and extracts from the leaves of this plant have already entered phase I clinical trials. In this communication, we have prepared a hyd...

Oncogene is one of the world’s leading cancer journals. It is published weekly and covers all aspects of the structure and function of Oncogenes.

The BJC is owned by Cancer Research UK, a charity dedicated to understanding the causes, prevention and treatment of cancer and to making sure that the best new treatments reach patients in the clinic as quickly as possible. The journal reflects these aims. It was founded more than fifty years ago and, from the start, its far-sighted mission was to...

Recent data suggest that hydroxytyrosol, a phenolic compound of virgin olive oils, has anticancer activity. This communication reports the synthesis of decyl and hexadecyl hydroxytyrosyl ethers, as well as the cytotoxic activity of hydroxytyrosol and a series of seven hydroxytyrosol alkyl ether derivatives against A549 lung cancer cells and MRC5 no...

5-Aza-2'-deoxycytidine (5-azadC) is a DNA methyltransferase (DNMT) inhibitor increasingly used in treatments of hematological diseases and works by being incorporated into DNA and trapping DNMT. It is unclear what DNA lesions are caused by 5-azadC and if such are substrates for DNA repair. Here, we identify that 5-azadC induces DNA damage as measur...

Phenolic compounds of Corema