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Artikel ; Online: Combination Therapy of Curcumin and Disulfiram Synergistically Inhibits the Growth of B16-F10 Melanoma Cells by Inducing Oxidative Stress.

Fontes, Sheila S / Nogueira, Mateus L / Dias, Rosane B / Rocha, Clarissa A Gurgel / Soares, Milena B P / Vannier-Santos, Marcos A / Bezerra, Daniel P

Biomolecules

2022 Band 12, Heft 11

Abstract: Oxidative stress plays a central role in the pathophysiology of melanoma. Curcumin (CUR) is a polyphenolic phytochemical that stimulates reactive oxygen species (ROS) production, while disulfiram (DSS) is a US FDA-approved drug for the treatment of ... ...

Abstract	Oxidative stress plays a central role in the pathophysiology of melanoma. Curcumin (CUR) is a polyphenolic phytochemical that stimulates reactive oxygen species (ROS) production, while disulfiram (DSS) is a US FDA-approved drug for the treatment of alcoholism that can act by inhibiting the intracellular antioxidant system. Therefore, we hypothesized that they act synergistically against melanoma cells. Herein, we aimed to study the antitumor potential of the combination of CUR with DSS in B16-F10 melanoma cells using in vitro and in vivo models. The cytotoxic effects of different combination ratios of CUR and DSS were evaluated using the Alamar Blue method, allowing the production of isobolograms. Apoptosis detection, DNA fragmentation, cell cycle distribution, and mitochondrial superoxide levels were quantified by flow cytometry. Tumor development in vivo was evaluated using C57BL/6 mice bearing B16-F10 cells. The combinations ratios of 1:2, 1:3, and 2:3 showed synergic effects. B16-F10 cells treated with these combinations showed improved apoptotic cell death and DNA fragmentation. Enhanced mitochondrial superoxide levels were observed at combination ratios of 1:2 and 1:3, indicating increased oxidative stress. In vivo tumor growth inhibition for CUR (20 mg/kg), DSS (60 mg/kg), and their combination were 17.0%, 19.8%, and 28.8%, respectively. This study provided data on the potential cytotoxic activity of the combination of CUR with DSS and may provide a useful tool for the development of a therapeutic combination against melanoma.
Mesh-Begriff(e)	Mice ; Animals ; Curcumin/pharmacology ; Curcumin/therapeutic use ; Disulfiram/pharmacology ; Cell Line, Tumor ; Superoxides/metabolism ; Mice, Inbred C57BL ; Melanoma, Experimental/metabolism ; Apoptosis ; Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; Oxidative Stress
Chemische Substanzen	Curcumin (IT942ZTH98) ; Disulfiram (TR3MLJ1UAI) ; Superoxides (11062-77-4) ; Antineoplastic Agents
Sprache	Englisch
Erscheinungsdatum	2022-10-31
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2701262-1
ISSN	2218-273X ; 2218-273X
ISSN (online)	2218-273X
ISSN	2218-273X
DOI	10.3390/biom12111600
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Duguetia pycnastera

Costa, Emmanoel V / de Souza, César A S / Galvão, Alexandre F C / Silva, Valdenizia R / Santos, Luciano de S / Dias, Rosane B / Rocha, Clarissa A Gurgel / Soares, Milena B P / da Silva, Felipe M A / Koolen, Hector H F / Bezerra, Daniel P

Molecules (Basel, Switzerland)

2022 Band 27, Heft 17

Abstract: Duguetia pycnastera Sandwith (Annonaceae) is a tropical tree that can be found in the Guyanas, Bolivia, Venezuela, and Brazil. In Brazil, it is popularly known as “ata”, “envira”, “envira-preta”, and “envira-surucucu”. In the present work, we ... ...

Abstract	Duguetia pycnastera Sandwith (Annonaceae) is a tropical tree that can be found in the Guyanas, Bolivia, Venezuela, and Brazil. In Brazil, it is popularly known as “ata”, “envira”, “envira-preta”, and “envira-surucucu”. In the present work, we investigated the in vitro and in vivo HepG2 cell growth inhibition capacity of D. pycnastera leaf essential oil (EO). The chemical composition of the EO was determined by GC−MS and GC−FID analyses. The alamar blue assay was used to examine the in vitro cytotoxicity of EO in cancer cell lines and non-cancerous cells. In EO-treated HepG2 cells, DNA fragmentation was measured by flow cytometry. The in vivo antitumor activity of the EO was assessed in C.B-17 SCID mice xenografted with HepG2 cells treated with the EO at a dosage of 40 mg/kg. Chemical composition analysis displayed the sesquiterpenes α-gurjunene (26.83%), bicyclogermacrene (24.90%), germacrene D (15.35%), and spathulenol (12.97%) as the main EO constituents. The EO exhibited cytotoxicity, with IC50 values ranging from 3.28 to 39.39 μg/mL in the cancer cell lines SCC4 and CAL27, respectively. The cytotoxic activity of the EO in non-cancerous cells revealed IC50 values of 16.57, 21.28, and >50 μg/mL for MRC-5, PBMC, and BJ cells, respectively. An increase of the fragmented DNA content was observed in EO-treated HepG2 cells. In vivo, EO displayed tumor mass inhibition activity by 47.76%. These findings imply that D. pycnastera leaf EO may have anti-liver cancer properties.
Mesh-Begriff(e)	Animals ; Annonaceae/chemistry ; Antineoplastic Agents, Phytogenic/chemistry ; Cell Line, Tumor ; Hep G2 Cells ; Humans ; Leukocytes, Mononuclear ; Mice ; Mice, SCID ; Oils, Volatile/chemistry ; Plant Leaves/chemistry
Chemische Substanzen	Antineoplastic Agents, Phytogenic ; Oils, Volatile
Sprache	Englisch
Erscheinungsdatum	2022-09-02
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27175664
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Antitumor Effect of

Galvão, Alexandre F C / Araújo, Morgana de S / Silva, Valdenizia R / Santos, Luciano de S / Dias, Rosane B / Rocha, Clarissa A Gurgel / Soares, Milena B P / Silva, Felipe M A da / Koolen, Hector H F / Zengin, Gokhan / Costa, Emmanoel V / Bezerra, Daniel P

Molecules (Basel, Switzerland)

2022 Band 27, Heft 14

Abstract: Guatteria ... ...

Abstract	Guatteria olivacea
Mesh-Begriff(e)	Animals ; Annonaceae ; Guatteria ; Humans ; Mice ; Mice, SCID ; Neoplasms ; Oils, Volatile/pharmacology ; Plant Leaves ; Reactive Oxygen Species
Chemische Substanzen	Oils, Volatile ; Reactive Oxygen Species
Sprache	Englisch
Erscheinungsdatum	2022-07-09
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules27144407
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Arsenic Trioxide Triggers Apoptosis of Metastatic Oral Squamous Cells Carcinoma with Concomitant Downregulation of GLI1 in Hedgehog Signaling.

Nogueira, Raphael Luís Rocha / de Araújo, Taís Bacelar Sacramento / Valverde, Ludmila Faro / Silva, Viviane Aline Oliveira / Cavalcante, Bruno Raphael Ribeiro / Rossi, Erik Aranha / Allahdadi, Kyan James / Dos Reis, Mitermayer Galvão / Pereira, Thiago Almeida / Coletta, Ricardo D / Bezerra, Daniel Pereira / de Freitas Souza, Bruno Solano / Dias, Rosane Borges / Rocha, Clarissa A Gurgel

Biomedicines

2022 Band 10, Heft 12

Abstract: Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of ... ...

Abstract	Given the lack of advances in Oral Squamous Cell Carcinoma (OSCC) therapy in recent years, pharmacological strategies to block OSCC-related signaling pathways have gained prominence. The present study aimed to evaluate the therapeutic potential of Arsenic Trioxide (ATO) concerning its antitumoral effects and the inhibition of the Hedgehog (HH) pathway in OSCC. Initially, ATO cytotoxicity was assessed in a panel of cell lines. Cell viability, cell cycle, death patterns, and cell morphology were analyzed, as well as the effect of ATO on the expression of HH pathway components. After the cytotoxic assay, HSC3 cells were chosen for all in vitro assays. ATO increased apoptotic cell death and nuclear fragmentation in the sub-G1 cell cycle phase and promoted changes in cell morphology. In addition, the reduced expression of GLI1 indicated that ATO inhibits HH activity. The present study provides evidence of ATO as an effective cytotoxic drug for oral cancer treatment in vitro.
Sprache	Englisch
Erscheinungsdatum	2022-12-19
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines10123293
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Tingenone and 22-hydroxytingenone target oxidative stress through downregulation of thioredoxin, leading to DNA double-strand break and JNK/p38-mediated apoptosis in acute myeloid leukemia HL-60 cells.

Rodrigues, Ana Carolina B da C / Bomfim, Larissa M / Neves, Sara P / Soares, Milena B P / Dias, Rosane B / Valverde, Ludmila F / Rocha, Clarissa A Gurgel / Costa, Emmanoel V / da Silva, Felipe M A / Rocha, Waldireny C / Koolen, Hector H F / Bezerra, Daniel P

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2021 Band 142, Seite(n) 112034

Abstract: Acute myeloid leukemia (AML) is the most lethal form of leukemia. Standard anti-AML treatment remains almost unchanged for decades. Tingenone (TG) and 22-hydroxytingenone (22-HTG) are quinonemethide triterpenes found in the Amazonian plant Salacia ... ...

Abstract	Acute myeloid leukemia (AML) is the most lethal form of leukemia. Standard anti-AML treatment remains almost unchanged for decades. Tingenone (TG) and 22-hydroxytingenone (22-HTG) are quinonemethide triterpenes found in the Amazonian plant Salacia impressifolia (Celastraceae), with cytotoxic properties in different histological types of cancer cells. In the present work, we investigated the anti-AML action mechanism of TG and 22-HTG in the AML HL-60 cell line. Both compounds exhibited potent cytotoxicity in a panel of cancer cell lines. Mechanistic studies found that TG and 22-HTG reduced cell growth and caused the externalization of phosphatidylserine, the fragmentation of internucleosomal DNA and the loss of mitochondrial transmembrane potential in HL-60 cells. In addition, pre-incubation with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, prevented TG- and 22-HTG-induced apoptosis, indicating cell death by apoptosis via a caspase-dependent pathway. The analysis of the RNA transcripts of several genes indicated the interruption of the cellular antioxidant system, including the downregulation of thioredoxin, as a target for TG and 22-HTG. The application of N-acetyl-cysteine, an antioxidant, completely prevented apoptosis induced by TG and 22-HTG, indicating activation of the apoptosis pathway mediated by oxidative stress. Moreover, TG and 22-HTG induced DNA double-strand break and phosphorylation of JNK2 (T183/Y185) and p38α (T180/Y182), and co-incubation with SP 600125 (JNK/SAPK inhibitor) and PD 169316 (p38 MAPK inhibitor) partially prevented apoptosis induced by TG and 22-HTG. Together, these data indicate that TG and 22-HTG are new candidate for anti-AML therapy targeting thioredoxin.
Mesh-Begriff(e)	Animals ; Antineoplastic Agents, Phytogenic/pharmacology ; Antioxidants/metabolism ; Apoptosis/drug effects ; Cell Line ; Cell Line, Tumor ; DNA Breaks, Double-Stranded/drug effects ; Down-Regulation/drug effects ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute/drug therapy ; Leukemia, Myeloid, Acute/genetics ; MAP Kinase Signaling System/drug effects ; Mice ; Oxidative Stress/drug effects ; Salacia/chemistry ; Thioredoxins/genetics ; Triterpenes/pharmacology ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemische Substanzen	Antineoplastic Agents, Phytogenic ; Antioxidants ; Triterpenes ; tingenin B (50656-68-3) ; tingenone (50802-21-6) ; Thioredoxins (52500-60-4) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24)
Sprache	Englisch
Erscheinungsdatum	2021-08-16
Erscheinungsland	France
Dokumenttyp	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2021.112034
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Ruthenium Complexes With Piplartine Cause Apoptosis Through MAPK Signaling by a p53-Dependent Pathway in Human Colon Carcinoma Cells and Inhibit Tumor Development in a Xenograft Model.

Baliza, Ingrid R S / Silva, Suellen L R / Santos, Luciano de S / Neto, João H Araujo / Dias, Rosane B / Sales, Caroline B S / Rocha, Clarissa A Gurgel / Soares, Milena B P / Batista, Alzir A / Bezerra, Daniel P

Frontiers in oncology

2019 Band 9, Seite(n) 582

Abstract: Ruthenium complexes with piplartine, [Ru(piplartine)(dppf)(bipy)]( ... ...

Abstract	Ruthenium complexes with piplartine, [Ru(piplartine)(dppf)(bipy)](PF
Sprache	Englisch
Erscheinungsdatum	2019-07-03
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.00582
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Ruthenium Complexes Containing Heterocyclic Thioamidates Trigger Caspase-Mediated Apoptosis Through MAPK Signaling in Human Hepatocellular Carcinoma Cells.

Neves, Sara P / de Carvalho, Nanashara C / da Silva, Monize M / Rodrigues, Ana Carolina B C / Bomfim, Larissa M / Dias, Rosane B / Sales, Caroline B S / Rocha, Clarissa A Gurgel / Soares, Milena B P / Batista, Alzir A / Bezerra, Daniel P

Frontiers in oncology

2019 Band 9, Seite(n) 562

Abstract: Herein, ruthenium complexes containing heterocyclic thioamidates [Ru(mmi)(bipy)(dppb)] ... ...

Abstract	Herein, ruthenium complexes containing heterocyclic thioamidates [Ru(mmi)(bipy)(dppb)]PF
Sprache	Englisch
Erscheinungsdatum	2019-07-09
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.00562
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Ru(II)-thymine complex causes DNA damage and apoptotic cell death in human colon carcinoma HCT116 cells mediated by JNK/p38/ERK1/2 via a p53-independent signaling.

Silva, Suellen L R / Baliza, Ingrid R S / Dias, Rosane B / Sales, Caroline B S / Rocha, Clarissa A Gurgel / Soares, Milena B P / Correa, Rodrigo S / Batista, Alzir A / Bezerra, Daniel P

Scientific reports

2019 Band 9, Heft 1, Seite(n) 11094

Abstract: Ru(II)-thymine complex [Ru( ... ...

Abstract	Ru(II)-thymine complex [Ru(PPh
Mesh-Begriff(e)	Apoptosis/drug effects ; Cell Line, Tumor ; Colon/drug effects ; Colon/metabolism ; Colonic Neoplasms/drug therapy ; Colonic Neoplasms/metabolism ; DNA Damage/drug effects ; HCT116 Cells ; Humans ; MAP Kinase Signaling System/drug effects ; Ruthenium/pharmacology ; Signal Transduction/drug effects ; Thymine/pharmacology ; Tumor Suppressor Protein p53/metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism
Chemische Substanzen	Tumor Suppressor Protein p53 ; Ruthenium (7UI0TKC3U5) ; p38 Mitogen-Activated Protein Kinases (EC 2.7.11.24) ; Thymine (QR26YLT7LT)
Sprache	Englisch
Erscheinungsdatum	2019-07-31
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-47539-0
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells.

Bomfim, Larissa M / de Araujo, Fênix A / Dias, Rosane B / Sales, Caroline B S / Rocha, Clarissa A Gurgel / Correa, Rodrigo S / Soares, Milena B P / Batista, Alzir A / Bezerra, Daniel P

Scientific reports

2019 Band 9, Heft 1, Seite(n) 11483

Abstract: Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu) ...

Abstract	Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)
Mesh-Begriff(e)	Animals ; Apoptosis/drug effects ; Caspases/metabolism ; Cell Proliferation/drug effects ; Coordination Complexes/pharmacology ; Coordination Complexes/therapeutic use ; DNA Breaks, Double-Stranded/drug effects ; Female ; HL-60 Cells ; Humans ; Leukemia, Promyelocytic, Acute ; MAP Kinase Signaling System/drug effects ; Mice ; Phosphorylation/drug effects ; Ruthenium/pharmacology ; Ruthenium/therapeutic use ; Thiouracil/analogs & derivatives ; Thiouracil/pharmacology ; Thiouracil/therapeutic use ; Xenograft Model Antitumor Assays
Chemische Substanzen	6-methyl-2-thiouracil ; Coordination Complexes ; Thiouracil (59X161SCYL) ; Ruthenium (7UI0TKC3U5) ; Caspases (EC 3.4.22.-)
Sprache	Englisch
Erscheinungsdatum	2019-08-07
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-019-47914-x
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: In vitro and in vivo inhibition of HCT116 cells by essential oils from bark and leaves of Virola surinamensis (Rol. ex Rottb.) Warb. (Myristicaceae).

Anunciação, Talita A da / Costa, Rafaela G A / Lima, Emilly J S P de / Silva, Valdenizia R / Santos, Luciano de S / Soares, Milena B P / Dias, Rosane B / Rocha, Clarissa A Gurgel / Costa, Emmanoel V / Silva, Felipe M A da / Koolen, Hector H F / Bezerra, Daniel P

Journal of ethnopharmacology

2020 Band 262, Seite(n) 113166

Abstract: Ethnopharmacological relevance: Virola surinamensis (Rol. ex Rottb.) Warb. (Myristicaceae), popularly known in Brazil as "mucuíba", "ucuúba", "ucuúba-branca" or "ucuúba do igapó", is a medicinal plant used to treat a variety of diseases, including ... ...

Abstract	Ethnopharmacological relevance: Virola surinamensis (Rol. ex Rottb.) Warb. (Myristicaceae), popularly known in Brazil as "mucuíba", "ucuúba", "ucuúba-branca" or "ucuúba do igapó", is a medicinal plant used to treat a variety of diseases, including infections, inflammatory processes and cancer. Aim of the study: In the present work, we investigated the chemical constituents and the in vitro and in vivo inhibition of human colon carcinoma HCT116 cells by essential oils obtained from the bark (EOB) and leaves (EOL) of V. surinamensis. Materials and methods: EOB and EOL were obtained by hydrodistillation and analyzed via gas chromatography with flame ionization detection and gas chromatography coupled to mass spectrometry. In vitro cytotoxic activity was determined in cultured cancer cells HCT116, HepG2, HL-60, B16-F10 and MCF-7 and in a non-cancerous cell line MRC-5 by the Alamar blue assay after 72 h of treatment. Annexin V/propidium iodide staining, mitochondrial transmembrane potential and cell cycle distribution were evaluated by flow cytometry in HCT116 cells treated with essential oils after 24 and 48 h of treatment. The cells were also stained with May-Grunwald-Giemsa to analyze cell morphology. In vivo antitumor activity was evaluated in C.B-17 SCID mice with HCT116 cells. Results: The main constituents in EOB were aristolene (28.0 ± 3.1%), α-gurjunene (15.1 ± 2.4%), valencene (14.1 ± 1.9%), germacrene D (7.5 ± 0.9%), δ-guaiene (6.8 ± 1.0%) and β-elemene (5.4 ± 0.6%). On the other hand, EOL displayed α-farnesene (14.5 ± 1.5%), β-elemene (9.6 ± 2.3%), bicyclogermacrene (8.1 ± 2.0%), germacrene D (7.4 ± 0.7%) and α-cubebene (5.6 ± 1.1%) as main constituents. EOB showed IC Conclusions: These data indicate V. surinamensis as possible herbal medicine in the treatment of colon cancer.
Mesh-Begriff(e)	Animals ; Antineoplastic Agents, Phytogenic/isolation & purification ; Antineoplastic Agents, Phytogenic/pharmacology ; Cell Survival/drug effects ; Cell Survival/physiology ; Dose-Response Relationship, Drug ; Female ; HCT116 Cells ; HL-60 Cells ; Hep G2 Cells ; Humans ; MCF-7 Cells ; Melanoma, Experimental ; Mice ; Mice, SCID ; Myristicaceae ; Oils, Volatile/isolation & purification ; Oils, Volatile/pharmacology ; Plant Bark ; Plant Leaves ; Xenograft Model Antitumor Assays/methods
Chemische Substanzen	Antineoplastic Agents, Phytogenic ; Oils, Volatile
Sprache	Englisch
Erscheinungsdatum	2020-07-27
Erscheinungsland	Ireland
Dokumenttyp	Journal Article
ZDB-ID	134511-4
ISSN	1872-7573 ; 0378-8741
ISSN (online)	1872-7573
ISSN	0378-8741
DOI	10.1016/j.jep.2020.113166
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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