GC/MS Analysis, Antioxidant Activity, and Antimicrobial Effect of Pelargonium peltatum (Geraniaceae).

In recent years, the increase in antibiotic resistance demands searching for new compounds with antimicrobial activity. Phytochemicals found in plants offer an alternative to this problem. The genus Pelargonium contains several species; some have commercial use in traditional medicine such as P. sinoides, and others such as P. peltatum are little studied but have promising potential for various applications such as phytopharmaceuticals. In this work, we characterized the freeze-dried extracts (FDEs) of five tissues (root, stem, leaf, and two types of flowers) and the ethyl acetate fractions from leaf (Lf-EtOAc) and flower (Fwr-EtOAc) of P. peltatum through the analysis by thin-layer chromatography (T.L.C.), gas chromatography coupled to mass spectrometry (GC-MS), phytochemicals quantification, antioxidant capacity, and antimicrobial activity. After the first round of analysis, it was observed that the FDE-Leaf and FDE-Flower showed higher antioxidant and antimicrobial activities compared to the other FDEs, for which FDE-Leaf and FDE-Flower were fractionated and analyzed in a second round. The antioxidant activity determined by ABTS showed that Lf-EtOAc and Fwr-EtOAc had the lowest IC50 values with 27.15 ± 1.04 and 28.11 ± 1.3 µg/mL, respectively. The content of total polyphenols was 264.57 ± 7.73 for Lf-EtOAc and 105.39 ± 4.04 mg G.A./g FDE for Fwr-EtOAc. Regarding the content of flavonoid, Lf-EtOAc and Fw-EtOAc had the highest concentration with 34.4 ± 1.06 and 29.45 ± 1.09 mg Q.E./g FDE. In addition, the minimum inhibitory concentration (M.I.C.) of antimicrobial activity was evaluated: Lf-EtOAc and Fwr-EtOAc were effective at 31.2 µg/mL for Staphylococcus aureus and 62.5 µg/mL for Salmonella enterica, while for the Enterococcus feacalis strain, Fwr-EtOAc presented 31.2 µg/mL of M.I.C. According to the GC-MS analysis, the main compounds were 1,2,3-Benzenetriol (Pyrogallol), with 77.38% of relative abundance in the Lf-EtOAc and 71.24% in the Fwr-EtOAc, followed by ethyl gallate (13.10%) in the Fwr-EtOAc and (Z)-9-Octadecenamide (13.63% and 6.75%) in both Lf-EtOAc and Fwr-EtOAc, respectively.

Association of the IL-10 gene rs1800872 (-592 C>A) polymorphism with breast cancer in a Mexican population.

PURPOSE: Interleukin 10 (IL-10) gene polymorphisms are associated with different types of cancer, but these associations are inconsistent. The purpose of this study was to determine the frequency and association of the rs1800872 IL-10 gene polymorphism in Mexican women with breast cancer (BC). METHODS: The rs1800872 polymorphism was genotyped in 368 BC patients and 320 control women using the polymerase chain reaction (PCR). RESULTS: The rs1800872 polymorphism was a risk factor for BC compared to controls and BC patients with genotypes CA (p=0.004) and AA, and in the recessive model (p=0.0002), dominant model (CA+AA; p=0.0001), and allele A ( p=0.0001). Additionally, differences were observed in BC patients with the CA and CAAA genotypes who had chemotherapy gastric and hematological toxicity (p=0.022) and tumor stage IV (p=0.013) as a risk factor. Genotypes were CA in breastfeeding (p=0.017), AA in gastric toxicity (p=0.048), and CAAA in tumor stage I-II (p=0.019) as protective risk factors. In BC carriers of: 1) CAAA genotype with tumor stage I-II and breast feeding (≥6 months), 2) CA genotype BC Luminal A with tumor stage I-II, 3) CA genotype BC Luminal B with breastfeeding (≥6 months), and 4) CAAA genotypes in BC HER2 with indices of cellular proliferation (Ki-67) that were elevated (≥20%), were considered to be protective factors in BC patients. CONCLUSION: The IL-10 gene rs1800872 polymorphism was associated with BC susceptibility in this sample from the Mexican population.

Association of the Del1518 Promoter (rs3730485) Polymorphism in the MDM2 Gene with Breast Cancer in a Mexican Population.

INTRODUCTION: The MDM2 gene plays an important role in tumorigenesis. The data on the Del1518 promoter polymorphism in the MDM2 gene have revealed associations with cancer. MATERIAL AND METHODS: We examined the role of the MDM2 Del1518 polymorphism through a comparison of the genotypes of 345 healthy Mexican women with those of 742 Mexican women with breast cancer (BC). RESULTS: The genotype frequencies of the MDM2 Del1518 polymorphism in controls and patients with BC were 64% and 55.5% for ins/ins, 32% and 31.5% for ins/del, and 4% and 13% for del/del, respectively. The obtained odds ratio (OR) was 3.26, with a 95% confidence interval (95% CI) of 1.86-5.72 and p=0.0001, for the del/del genotype. An association was evident when we examined the distribution of the del/del genotype in patients with elevated levels of transaminase SGPT (OR=2.268; 95% CI=1.40-3.65; p=0.0001). Additionally, we observed an association of the genotypes del/del - ins/del in menopausal patients with BC with the following characteristics: tobacco consumption (OR = 1.93, 95% CI = 1.07-3.4, p=0.025), pregnancy loss (OR=2.44, 95% CI=1.37-4.35, p=0.0024), obesity (I-IV) (OR=1.8, 95% CI=1.1-2.9, p= 0.018), and elevated serum glucose levels (OR=3.72, 95% CI=2.0-6.85, p=0.0001). CONCLUSIONS: The MDM2 Del1518 polymorphism was associated with BC susceptibility, particularly in menopausal patients with BC who reported tobacco consumption, pregnancy loss, obesity and high glucose levels in the analyzed Mexican population.

Artemisia dracunculus Extracts Obtained by Organic Solvents and Supercritical CO2 Produce Cytotoxic and Antitumor Effects in Mice with L5178Y Lymphoma.

We investigated the cytotoxic and antitumor effects of nine leaf extracts from Artemisia dracunculus (Tarragon). Five extracts were obtained using different organic solvents and four by supercritical CO2. The cytotoxic effects were expressed as IC50 in 100, 80, 80, 100, and 80 µg/mL by respective solvents: hexane, ethyl acetate, acetone, ethanol, and acetonitrile in L5178Y lymphoma cells. For supercritical CO2 extract A, IC50 was 100 µg/mL; for extracts C and D, IC50 was 150 µg/mL. The antitumor activity was assessed through a tumor growth inhibition test that measured ascites fluid volume and tumor cell counts of BALB/c mice (2 × 104 cells L5178Y i.p.). Twenty-four hours after inoculation, mice were treated with 100 mg/kg of acetonitrile extract or extract SF-A daily for 15 days in independent groups of five mice, using two administration routes. We observed tumor evolution with and without treatment. Without treatment, tumor evolution was 17,969 × 106 ± 5485 L5178Y cells in 2.6 mL ascites volume, whereas the orally treated acetonitrile extract group showed 0.1 × 106 ± 0.07 L5178Y cells (P < .05). The oral SF-A group showed 12.9 × 106 ± 243 L5178Y cells, and intraperitoneal (i.p.)-treated SF-A group showed 0.1 × 106 ± 0.05 L5178Y cells (P < .05) without any ascites volume development. The acetonitrile extract contains abundant polyphenols and possibly a flavone with antioxidant activity. The SF-A contains abundant alkamides. Both extracts are complexes and the identity of the compounds responsible for observed antitumor activity remains unknown.

Intron 4 VNTR (4a/b) polymorphism of the endothelial nitric oxide synthase gene is associated with breast cancer in Mexican women.

The endothelial nitric oxide synthase (eNOS) gene plays an important role in several biological functions. Polymorphisms of the eNOS gene have been associated with cancer. It has been suggested that the VNTR 4 a/b polymorphism may affect the expression of eNOS and contributes to tumor promotion in the mammary gland. We examined the role of the eNOS4 a/b polymorphism by comparing the genotypes of 281 healthy Mexican women with the genotypes of 429 Mexican women with breast cancer (BC). The observed genotype frequencies for control and BC patients were 0.6% and 0.7% for a/a (polymorphic); 87% and 77% for a/a (wild type); and 12% and 22% for a/b respectively. We found that the odds ratio (OR) was 1.9, with a 95% confidence interval (95%CI) of 1.29-2.95, P = 0.001 for genotypes a/a-a/b, b/c. The association was also evident when comparing the distribution of the a/a-a/b genotypes in patients with high levels of glutamate-oxaloacetate transaminase (SGOT) (OR, 1.93; 95% CI, 1.14-3.28; P = 0.015); undergoing menopause with high levels of SGOT (OR, 2.0; 95% CI, 1.1-3.84); and with high levels of glutamic-pyruvic transaminase (SGPT) (OR, 3.5; 95% CI, 1.56-8.22). The genotypes a/a-a/b are associated with BC susceptibility in the analyzed samples from the Mexican population.

Effect of ditaxin and heteranthin and inhibitory effect of Ditaxis heterantha extract on L5178Y tumor development in mice.

Ditaxis heterantha seeds are used as spices for flavoring and coloring food. Two new apocarotenoids derived from the seeds, heteranthin and ditaxin, were evaluated for their in vitro cytotoxic effects in murine lymphoma cells lines. Bioabsorption in mice and preventive and antitumor effects of the apocarotenoids were determined. Ditaxin and heteranthin showed cytotoxic effects in vitro against murine malignant cells and normal splenocyte cells. The 50% inhibitory concentration (IC(50)) for ditaxin in splenocytes was 0.1825 mM; in L5178Y, the IC(50) was 0.1923 mM. The heteranthin IC(50) in splenocytes was 0.1325 mM; in L5178Y, the value was 0.3889 mM. The maximum ditaxin plasma concentration was found after 2 hours of administration (mean±standard deviation, 7.5±2.05 µg/mL). Oral administration of the D. heterantha extract (100 mg/kg per day) for 14 days after the L5178Y lymphoma cell implantation showed no significant effect compared with groups that were not pretreated. However, tumor inhibition in groups treated intraperitoneally before inoculation with the L5178Y cells showed a significant difference (P<.001) compared with the groups not pretreated.

Polyamines as biomarkers of the antitumoral activity of Bursera fagaroides

En células normales y tumorales las poliaminas (Pas) putresina (Pu), espermidina (Spd) y espermina (Spm) son requeridas en múltiples funciones fundamentales del ciclo celular. Altos niveles de Pas han sido reportados en varios tipos de cáncer, por lo que han sido propuestas como biomarcadores del desarrollo tumoral. En el presente trabajo se reporta su utilidad como biomarcadores de la evolución del linfoma murino L5178Y en diferentes fluidos, células y tejidos. Los hallazgos también fueron aplicados al seguimiento del efecto antitumoral de Bursera fagaroides, ya reportado previamente. Se utilizó cromatografía de intercambio iónico para determinar los niveles de Pas en orina, células peritoneales linfocitos circulantes, esplenocitos, mesotelio e hígado de ratones BALB/c a los 10, 17 y 24 días de evolución del tumor y de ratones tratados con el exacto hidroalcohólico de la corteza de B. fagaroides administrado por vía oral o intaperitonealmente (i.p) los niveles urinarios de Spd no fueron detectables, mientras que el incremento de Pu en orina es el mejor biomarcador del crecimiento del linfoma. Además los niveles urinarios de Pu disminuyeron significativamente en ratones tratados intraperitonealmente con B. fagoroides, lo cual refuerza resultados anteriores. En este modelo la variación de los niveles urinarios de Pu es un biomarcador efectivo del desarrollo neoplástico, dado que permite seguir la evolución del linfoma L5178Y. Además, proporciona una herramienta para estudiar in vivo, el efecto antitumoral de B. fagaroides y de otros fármacos.