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5. Actividad citotóxica del extracto etanólico de gnaphalium spicatum 'keto keto' en cultivos de líneas celulares tumorales humanas

Author

Callacondo-Riva, David, Quispe-Mauricio, Angel, Lindo-Gamarra, Selamir, and Vaisberg, Abraham J.

Subjects
lcsh:R5-920, Fitoterapia, Agentes antineoplásicos, Plantas medicinales, lcsh:R, Citotoxicity, lcsh:Medicine, Citotoxicidad, Medicinal plats, Phytotheraphy, Cultivo celular, Antineoplastic agents, Cell culture, lcsh:Medicine (General)
Abstract

Objetivos. Evaluar la actividad citotóxica de extractos etanólicos de raíces, tallos, hojas y flores de Gnaphalium spicatum sobre algunas líneas celulares tumorales humanas. Materiales y métodos. Las líneas celulares HT-29, H-460, MCF-7, M-14, PC-3, DU-145, K-562, y 3T3, fueron expuestas a cuatro concentraciones de extractos etanólicos de raíces, tallos, hojas y flores de Gnaphalim spicatum, asimismo, a diferentes concentraciones de cisplatino, que se usó como control positivo. Se halló los porcentajes de crecimiento en 48 horas. Luego se determinó la concentración inhibitoria 50 (CI50) mediante análisis de regresión lineal, el índice de selectividad de cada muestra y finalmente, la relación dosis-respuesta entre las concentraciones de los extractos y cisplatino, con los porcentajes de crecimiento. Resultados. El extracto etanólico de las raíces de Gnaphalium spicatum mostró mayor actividad citotóxica en la líneas celulares MCF-7 y K-562. Los CI50 en μg/mL fueron de 98 (r= -0,98 p < 0,01) y 46 (r= -0,97 p < 0,01), respectivamente. Asimismo, su citotoxicidad en la lνnea celular 3T3 fue de 215 (r= 0,97 p a 0,250 mg/mL en todas la líneas celulares evaluadas. Conclusiones. Los extractos etanólicos de tallos, hojas y flores de Gnaphalium spicatum no mostraron actividad citotóxica en este bioensayo. Los extractos de raíces mostraron citotoxicidad en las todas las líneas celulares tumorales, excepto en M-14. Además fueron menos citotóxicos en relación al cisplatino en la línea celular 3T3. Objectives. To evaluate the cytotoxic activity ethanolic extracts of roots, stems, leaves and flowers of Gnaphalium spicatum in some human tumor cell lines. Material and methods. The following cell lines: HT-29, H-460, MCF-7, M-14, PC-3, DU-145, K-562, and 3T3, were exposed to four different concentrations of ethanolic extracts from roots, stems, leaves and flowers of Gnaphalium spicatum, and also to different concentrations of cisplatin, which was used as a positive control. Percentage growth was assessed after 48 hours. The minimal inhibitory concentration for 50 per cent of the cells (IC50) was determined using linear regression analysis; also, the selectivity index for each sample and the dose-response relationship between the extract concentrations and cisplatin, as well as growth percentages were determined. Results. The ethanolic extract of Gnaphalium spicatum roots showed its highest cytotoxic activity in MCF-7 and K-562 cell lines. IC50 values, expressed in μg/mL, were 98 (r=-0.98; p 0.250 mg/mL in every cell lines tested. Conclusions. The ethanolic extracts of stems, leaves and flowers of Gnaphalium spicatum did not show cytotoxic activity in this bioassay. The extract from roots showed cytotoxicity in all tumor cell lines, except in M-14. Furthermore, it was less cytotoxic than cisplatin in 3T3 cell line.

Published
2008

17. MALDI-TOF MS characterization of proanthocyanidins from cranberry fruit (Vaccinium macrocarpon) that inhibit tumor cell growth and matrix metalloproteinase expressionin vitro

Author

Neto, Catherine C, primary, Krueger, Christian G, additional, Lamoureaux, Toni L, additional, Kondo, Miwako, additional, Vaisberg, Abraham J, additional, Hurta, Robert AR, additional, Curtis, Shannon, additional, Matchett, Michael D, additional, Yeung, Horace, additional, Sweeney, Marva I, additional, and Reed, Jess D, additional

Published
2005
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29. Physangulidine A, a Withanolide from Physalis angulata, Perturbs the Cell Cycle and Induces Cell Death by Apoptosis in Prostate Cancer Cells

Author

Reyes-Reyes, E. Merit, Jin, Zhuang, Vaisberg, Abraham J., Hammond, Gerald B., and Bates, Paula J.

Abstract

Recently, our group reported the discovery of three new withanolides, physangulidines A–C, from Physalis angulata. In this study, the biological effects of physangulidine A (1), which was the most active and abundant of the three new constituents, are described. It was found that 1significantly reduces survival in clonogenic assays for two hormone-independent prostate cancer cell lines. Flow cytometry and confocal microscopy studies in DU145 human prostate cancer cells indicated that 1induces cell cycle arrest in the G2/M phase and causes defective mitosis. It was determined also that 1produces programed cell death by apoptosis, as evidenced by biochemical markers and distinct changes in cell morphology. These results imply that the antimitotic and proapoptotic effects of 1may contribute significantly to the biological activities and potential medicinal properties of its plant of origin.

Published
2013
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31. Cytotoxic and Anti-infective Phenolic Compounds Isolated from Mikania decora and Cremastosperma microcarpum.

Author

Aponte, José C., Zhuang Jin, Vaisberg, Abraham J., Castillo, Denis, Málaga, Edith, Lewis, Walter H., Sauvain, Michel, Gilman, Robert H., and Hammond, Gerald B.

Subjects
CHROMATOGRAPHIC analysis, ANTI-infective agents, ANTINEOPLASTIC agents, HIGH performance liquid chromatography, LEISHMANIA, MOLECULAR structure, PROTOZOA, RESEARCH funding, TOXICITY testing, PLANT extracts, PHARMACODYNAMICS
Abstract

An anticancer-bioassay guided isolation of the ethanol extract and fractions of two plants from the Peruvian rainforest, Mikania decora and Cremastosperma microcarpum, led to the characterization of one abundant diterpene, ent-pimara-8(14),15-dien- 19-oic acid (1), three thymol derivatives, 10-acetoxy-8,9-dehydro- 6-methoxythymol butyrate (2), 10-acetoxy-8,9-epoxy-6- methoxythymol isobutyrate (3), and acetylschizoginol (4), aswell as one neolignan, (±)-trans-dehydrodiisoeugenol (5). Only the latter was isolated from C. microcarpum. These compounds exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 3 and 4 were also investigated for their in vitro antileishmanial and trypanocidal activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes. [ABSTRACT FROM AUTHOR]

Published
2011
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34. Plagiochiline A Inhibits Cytokinetic Abscission and Induces Cell Death.

Author

Stivers, Nicole S., Islam, Ashraful, Reyes-Reyes, Elsa M., Casson, Lavona K., Aponte, José C., Vaisberg, Abraham J., Hammond, Gerald B., and Bates, Paula J.

Subjects
PROSTATE cancer treatment, LEUKEMIA diagnosis, CELL death, CANCER cells, FLUORESCENCE microscopy
Abstract

We previously reported on the isolation and biological activities of plagiochiline A (1), a 2,3-secoaromadendrane-type sesquiterpenoid from the Peruvian medicinal plant, Plagiochila disticha. This compound was found to have antiproliferative effects on a variety of solid tumor cell lines, as well as several leukemia cell lines. Other researchers have also noted the cytotoxicity of plagiochiline A (isolated from different plant species), but there are no prior reports regarding the mechanism for this bioactivity. Here, we have evaluated the effects of plagiochiline A on cell cycle progression in DU145 prostate cancer cells. A cell cycle analysis indicated that plagiochiline A caused a significant increase in the percentage of cells in the G2/M phase when compared with control cells. When cells were stained and observed by fluorescence microscopy to examine progress through the mitotic phase, we found a significant increase in the proportion of cells with features of late cytokinesis (cells connected by intercellular bridges) in the plagiochiline A-treated samples. These results suggest that plagiochiline A inhibits cell division by preventing completion of cytokinesis, particularly at the final abscission stage. We also determined that plagiochiline A reduces DU145 cell survival in clonogenic assays and that it induces substantial cell death in these cells. [ABSTRACT FROM AUTHOR]

Published
2018
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38. Ethnobotany, phytochemistry and pharmacology of Uncaria (Rubiaceae)

Author

Heitzman, Mary E., Neto, Catherine C., Winiarz, Elizabeth, Vaisberg, Abraham J., and Hammond, Gerald B.

Subjects
*UNCARIA, *ETHNOBOTANY, *USEFUL plants, *BOTANICAL chemistry, *PHARMACOLOGY
Abstract

Abstract: The Uncaria genus is an important source of medicinal natural products, particularly alkaloids and triterpenes. The collected information is an attempt to cover the more recent developments in the ethnobotany, pharmacology and phytochemistry of this genus. During the past 20 years, alkaloids, terpenes, quinovic acid glycosides, flavonoids and coumarins have been isolated from Uncaria. Fifty-three novel structures are reported in this review. The species in which the largest number of compounds has been identified is the Peruvian Uncaria tomentosa or ‘cat’s claw.’ Pharmacological studies are described according to cytotoxicity, anti-inflammatory, antiviral, immunostimulation, antioxidant, CNS-related response, vascular, hypotensive, mutagenicity and antibacterial properties. The potential for development of leads from Uncaria continues to grow, particularly in the area of immunomodulatory, anti-inflammatory and vascular-related conditions. The information summarized here is intended to serve as a reference tool to practitioners in the fields of ethnopharmacology and natural products chemistry. [Copyright &y& Elsevier]

Published
2005
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39. Discovery of Novel (Imidazo[1,2-a]pyrazin-6-yl)ureas as Antiproliferative Agents Targeting P53 in Non-small Cell Lung Cancer Cell Lines.

Author

Bazin MA, Rousseau B, Marhadour S, Tomasoni C, Evenou P, Piessard S, Vaisberg AJ, Ruchaud S, Bach S, Roussakis C, and Marchand P

Subjects
Animals, BALB 3T3 Cells, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung genetics, Cell Line, Tumor, Cell Proliferation drug effects, Humans, Lung Neoplasms drug therapy, Lung Neoplasms genetics, Mice, Tumor Suppressor Protein p53 genetics, Antineoplastic Agents pharmacology, Imidazoles pharmacology, Pyrazines pharmacology, Urea analogs & derivatives, Urea pharmacology
Abstract

A series of (imidazo[1,2-a]pyrazin-6-yl)ureas were synthesized through 6-aminoimidazo[1,2-a]pyrazine as a key intermediate. 1-(Imidazo[1,2-a]pyrazin-6-yl)-3-(4-methoxy - phenyl)urea displayed a cytostatic activity against a non-small cell lung cancer cell line and was chosen for further mechanistic studies. Growth kinetics highlighted a selective dose-dependent response of P53-mutant NSCLC-N6-L16 cell line and overexpression of TP53 gene induced by this compound. These pharmacological data suggest a promising reactivation of p53 mutant in NSCLC-N6-L16 cell line., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Published
2016

40. Cytotoxic and anti-infective sesquiterpenes present in Plagiochila disticha (Plagiochilaceae) and Ambrosia peruviana (Asteraceae).

Author

Aponte JC, Yang H, Vaisberg AJ, Castillo D, Málaga E, Verástegui M, Casson LK, Stivers N, Bates PJ, Rojas R, Fernandez I, Lewis WH, Sarasara C, Sauvain M, Gilman RH, and Hammond GB

Subjects
Cell Line, Tumor, Drug Evaluation, Preclinical, Humans, Peru, Plants, Medicinal chemistry, Anti-Infective Agents isolation & purification, Antineoplastic Agents, Phytogenic isolation & purification, Asteraceae chemistry, Azulenes isolation & purification, Epoxy Compounds isolation & purification, Pyrans isolation & purification, Sesquiterpenes isolation & purification
Abstract

A pharmacological screening of the ethanol extract and fractions of two Peruvian medicinal plants, Plagiochila disticha and Ambrosia peruviana, led to the isolation and characterization of three ENT-2,3-secoaromadendrane-type sesquiterpenoids, named plagiochiline A ( 1), I ( 2), and R ( 3), as well as of two pseudoguaianolids, damsin ( 4) and confertin ( 5), which exhibited significant cytotoxic activity against a panel of human tumor cell lines. Compounds 1, 4, and 5 were also investigated for their in vitro antileishmanial, trypanocidal, and antituberculosis activity against Leishmania amazonensis axenic amastigotes and Trypanosoma cruzi trypomastigotes, as well as against MDR and sensitive strains of Mycobacterium tuberculosis, respectively., (Georg Thieme Verlag KG Stuttgart. New York.)

Published
2010
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41. Anti-infective and cytotoxic compounds present in Blepharodon nitidum.

Author

Aponte JC, Estevez Y, Gilman RH, Lewis WH, Rojas R, Sauvain M, Vaisberg AJ, and Hammond GB

Subjects
Cell Line, Tumor, Humans, Molecular Structure, Anti-Infective Agents chemistry, Anti-Infective Agents pharmacology, Antineoplastic Agents, Phytogenic chemistry, Antineoplastic Agents, Phytogenic pharmacology, Apocynaceae chemistry
Abstract

A pharmacological screening of the ethanol extract and fractions of Blepharodon nitidum led to the isolation of fourteen compounds, two of which, 24-hydroperoxycycloart-25-en-3beta-ol and 25-hydroperoxycycloart-23-en-3beta-ol, exhibited in vitro anti- Mycobacterium tuberculosis and antileishmanial activities, as well as significant cytotoxic activity against a panel of human tumor cell lines.

Published
2008
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42. Isolation of cytotoxic metabolites from targeted peruvian amazonian medicinal plants.

Author

Aponte JC, Vaisberg AJ, Rojas R, Caviedes L, Lewis WH, Lamas G, Sarasara C, Gilman RH, and Hammond GB

Subjects
Antineoplastic Agents, Phytogenic chemistry, Drug Screening Assays, Antitumor, Humans, Microbial Sensitivity Tests, Molecular Structure, Pentacyclic Triterpenes, Peru, Triterpenes chemistry, Tumor Cells, Cultured, Betulinic Acid, Antineoplastic Agents, Phytogenic isolation & purification, Antineoplastic Agents, Phytogenic pharmacology, Mycobacterium tuberculosis drug effects, Plants, Medicinal chemistry, Strychnos chemistry, Triterpenes isolation & purification, Triterpenes pharmacology
Abstract

The antiproliferative bioassay-guided fractionation of five Peruvian plants, Doliocarpus dentatus, Picramnia sellowii, Strychnos mitscherlichii, Iryanthera juruensis, and Croton alnifolius, led to the isolation and identification of their different major cytotoxic constituents, betulinic acid (1), nataloe-emodin (2), bisnordihydrotoxyferine (4), 2',4'-dihydroxy-6'-methoxy-3,4-methylenedioxydihydrochalcone (5), and 2',4'-dihydroxy-4,6'-dimethoxydihydrochalcone (6) and 12-O-tetradecanoylphorbol-13-acetate (7), respectively. Eight human tumor cell lines and two nontumorigenic cell lines were used in this investigation. Their in vitro activity against Mycobacterium tuberculosis is also reported.

Published
2008
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