Network Pharmacology Uncovers Anticancer Activity of Mammea-Type Coumarins from Calophyllum brasiliense.

Abstract:

:Mammea-type coumarins are a particular type of secondary metabolites biosynthesized by the tropical rainforest tree Calophyllum Brasiliense, which is distributed from South America to Mexico. Particularly, mammea A/BA and A/BB (alone or as a mixture) possess biological properties such as cytotoxic and antitumoral activities, however, most of its molecular targets remain unknown. In this context, novel bioinformatic approaches, such as network pharmacology analysis, have been successfully used in herbal medicine to accelerate research in this field, and the support of experimental validations has been shown to be quite robust. In the present study, we performed a network pharmacology analysis to assess the possible molecular biological networks that interact with mammea A/BA and A/BB. Moreover, we validated the most relevant networks experimentally in vitro on K562 cancer cells. The results of the network pharmacology analysis indicate that mammea A/BA and A/BB interacts with cell death, PI3K/AKT, MAPK, Ras, and cancer pathways. The in vitro model shows that mammea A/BA and A/BB induce apoptosis through the overexpression of the proapoptotic proteins Bax and Bak, disrupt the autophagic flux as seen by the cytosolic accumulation of LC3-II and p62, disrupting the mitochondria ultrastructure and concomitantly increase the intracellular calcium concentration. Additionally, docking analysis predicted a possible interaction with a rapamycin-binding domain of mTOR. In conclusion, we validated network pharmacology analysis and report, for the first time, that mammea A/BA and A/BB coumarins induce apoptosis through the inhibition of the autophagic flux, possibly interacting with mTOR.

journal_name

Planta Med

journal_title

Planta medica

authors

Gómez-Verjan JC,Rivero-Segura NA,Estrella-Parra E,Rincón-Heredia R,Madariaga-Mazón A,Flores-Soto E,González-Meljem M,Cerbón M,Reyes-Chilpa R

doi

10.1055/a-0660-0236

subject

Has Abstract

pub_date

2019-01-01 00:00:00

pages

14-23

issue

1

eissn

0032-0943

issn

1439-0221

journal_volume

85

pub_type

杂志文章
  • New Phenolic Derivatives from Galeola faberi.

    abstract::Seven phenolic derivatives, 2,4-bis(4-hydroxybenzyl)phenol ( 1), bis[4(beta- D-glucopyranosyloxy)-benzyl] ( S)-(-)-2-isopropylmalate ( 2), bis[4-(beta- D-gluco-pyranosyloxy)benzyl] ( S)-(-)-2-sec-butylmalate ( 3), 4-hydroxybenzyaldehyde ( 4), 4,4'-dihydroxydiphenyl-methane ( 5), 4-hydroxybenzyl alcohol ( 6), and 4-(be...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2006-959702

    authors: Yi-Ming L,Zhuo-Lun Z,Yong-Fu H

    更新日期:1993-08-01 00:00:00

  • Gingerols of Zingiber officinale enhance glucose uptake by increasing cell surface GLUT4 in cultured L6 myotubes.

    abstract::In this study we investigate the active constituents of the rhizome of Zingiber officinale, Roscoe (ginger) and determine their activity on glucose uptake in cultured L6 myotubes and the molecular mechanism underlying this action. Freeze-dried ginger powder was extracted with ethyl acetate (1 kg/3 L) to give the total...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-0032-1315041

    authors: Li Y,Tran VH,Duke CC,Roufogalis BD

    更新日期:2012-09-01 00:00:00

  • 11-deoxyalisol C and alisol D: new protostane-type triterpenoids from Alisma plantago-aquatica.

    abstract::New protostane-type triterpenes, 11-deoxyalisol C and alisol D, have been isolated from the rhizomes of ALISMA PLANTAGO-AQUATICA, and their structures have been elucidated on the basis of spectral and chemical data. ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2006-962495

    authors: Fukuyama Y,Pei-Wu G,Rei W,Yamada T,Nakagawa K

    更新日期:1988-10-01 00:00:00

  • Rational and Efficient Preparative Isolation of Natural Products by MPLC-UV-ELSD based on HPLC to MPLC Gradient Transfer.

    abstract::In natural product research, the isolation of biomarkers or bioactive compounds from complex natural extracts represents an essential step for de novo identification and bioactivity assessment. When pure natural products have to be obtained in milligram quantities, the chromatographic steps are generally labourious an...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-0035-1545912

    authors: Challal S,Queiroz EF,Debrus B,Kloeti W,Guillarme D,Gupta MP,Wolfender JL

    更新日期:2015-11-01 00:00:00

  • Berberine inhibits cell growth and mediates caspase-independent cell death in human pancreatic cancer cells.

    abstract::Pancreatic cancer is one of the most aggressive human malignancies with an increasing incidence worldwide. In addition to the poor survival rates, combinations using gemcitabine as a backbone have failed to show any benefit beyond monotherapy. These facts underscore an urgent need for novel therapeutic options and mot...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-0030-1249931

    authors: Pinto-Garcia L,Efferth T,Torres A,Hoheisel JD,Youns M

    更新日期:2010-08-01 00:00:00

  • Accumulation of hydrolyzable tannins by Aleurites fordii callus culture.

    abstract::A callus culture of Aleurites fordii Hemsley (Euphorbiaceae) producing five galloylglucoses and an ellagitannin, geraniin, was established. The production of pentagalloylglucose was remarkably enhanced under light irradiation compared with that in the dark. Cell growth and tannin production were also greatly affected ...

    journal_title:Planta medica

    pub_type: 信件

    doi:10.1055/s-2002-36348

    authors: Taniguchi S,Uechi K,Kato R,Ito H,Hatano T,Yazaki K,Yoshida T

    更新日期:2002-12-01 00:00:00

  • Effects of propolis crude hydroalcoholic extract on chromosomal aberrations induced by doxorubicin in rats.

    abstract::Propolis has been reported to display a broad spectrum of biological activities such as anticancer, antioxidant, anti-inflammatory, antibiotic and antifungal properties, among others. There is great interest not only in the determination of the chemical composition of propolis but also in the understanding of the mech...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-993737

    authors: Tavares DC,Lira WM,Santini CB,Takahashi CS,Bastos JK

    更新日期:2007-12-01 00:00:00

  • [Comparative study of two medicinal Cucurbitaceae].

    abstract::Comparative study of the seeds of two Cucurbitaceae Momordica charantia L. and Herpetospermum caudigerum Wall. shows and important difference for their metabolism concerning particularly aspartic acid. Momordica can produce vicin, while for Herpetospermum, this amino acid would give asparagin. In the other hand, betwe...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-971211

    authors: Barron D,Kaouadji M,Mariotte AM

    更新日期:1982-11-01 00:00:00

  • Assessment of cannabinoids content in micropropagated plants of Cannabis sativa and their comparison with conventionally propagated plants and mother plant during developmental stages of growth.

    abstract::Gas chromatography-flame ionization detection (GC-FID) was used to assess the chemical profile and quantification of cannabinoids to identify the differences, if existing, in the chemical constituents of in vitro propagated plants (IVP), conventionally grown plants (VP) and indoor grown mother plants (MP-Indoor) of a ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-0029-1240628

    authors: Chandra S,Lata H,Mehmedic Z,Khan IA,ElSohly MA

    更新日期:2010-05-01 00:00:00

  • Extracellular polysaccharides produced by suspension-cultured cells from Digitalis lanata.

    abstract::Extracellular polysaccharides (ECP) were isolated in yields of up to 4 mg/ml from the culture media of suspension-cultured cells from Digitalis lanata Ehrh. ECP content was increasing continuously over the first ten days of cultivation and then stayed constant until day 20. ECP were fractionated by ion-exchange chroma...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2006-957730

    authors: Hensel A,Schmidgall J,Kreis W

    更新日期:1997-10-01 00:00:00

  • Structure-activity relationship of triterpenes and triterpenoid glycosides against tobacco mosaic virus.

    abstract::A new activity of triterpenes and triterpenoid glycosides against phytovirus has been found. Based on the anti-TMV replication activity in vivo, 47 triterpenes and triterpenoid glycosides were screened through the leaf-disk method together with indirect ELISA. Structure-activity relationships were analyzed according t...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-990263

    authors: Zhang ZK,Ouyang MA,Wu ZJ,Lin QY,Xie LH

    更新日期:2007-11-01 00:00:00

  • New Clerodane Derivatives from Teucrium scordium.

    abstract::A reinvestigation of the aerial parts of TEUCRIUM SCORDIUM afforded in addition to several known diterpenes five new clerodane derivatives, all closely related to teucrin. The structures and the stereochemistry were elucidated by high resolution (1)H-NMR spectroscopy. ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-969508

    authors: Jakupovic J,Baruah RN,Bohlmann F,Quack W

    更新日期:1985-08-01 00:00:00

  • Cytotoxic activity of Amaryllidaceae alkaloids.

    abstract::25 Amaryllidaceae alkaloids belonging to different skeletal types were evaluated for their cytotoxic activity against one murine non-tumoral cell line (LMTK) and two human tumoral cell lines (Molt4 and HepG2) according to established protocols. Significant differences of activity related with the type of skeleton of t...

    journal_title:Planta medica

    pub_type: 信件

    doi:10.1055/s-2006-958007

    authors: Weniger B,Italiano L,Beck JP,Bastida J,Bergoñon S,Codina C,Lobstein A,Anton R

    更新日期:1995-02-01 00:00:00

  • Studies on hernandiaceae VI. Lignans and alkaloids of Hernandia guianensis.

    abstract::The lignoidic and alkaloidal content of the leaves, stem barks and root barks of H. GUIANENSIS has been studied; two aryltetrahydronaphthalenes, two dibenzylbutyrolactones and nine alkaloids are isolated. All components are identified by means of the spectral analysis. Eight alkaloids are aporphines and nor-aporphines...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-969610

    authors: Richomme P,Lavault M,Jacquemin H,Bruneton J

    更新日期:1984-02-01 00:00:00

  • Cytotoxic limonoids from Melia azedarach.

    abstract::Five new compounds (1-5), including two limonoids, one triterpenoid, one steroid, and one sesquiterpenoid, along with nine known limonoids (6-14), were isolated from the bark of Melia azedarach. The structures of the new compounds were elucidated by 2D NMR spectroscopy and mass spectrometry. The isolated compounds as ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-0032-1328069

    authors: Yuan CM,Zhang Y,Tang GH,Li Y,He HP,Li SF,Hou L,Li XY,Di YT,Li SL,Hua HM,Hao XJ

    更新日期:2013-01-01 00:00:00

  • Molecular authentication of the traditional dai medicinal plant Croton caudatus.

    abstract::Croton caudatus is an important species in Dai folk medicine. Some other Croton species, in particular, C. kongensis, C. cascarilloides, C. crassifolius, C. lachnocarpus and C. olivaceus are often marketed as C. caudatus, and thus, the therapeutic effects of C. caudatus are not achieved. The respective morphological f...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-967197

    authors: Xue HG,Zhou SD,He XJ,Yu Y

    更新日期:2007-06-01 00:00:00

  • Clonal propagation of Isoplexis canariensis.

    abstract::Isoplexis is a plant genus closely related to Digitalis. Members of this genus contain cardenolides considered more "primitive" than those present in Digitalis. Isoplexis plants, tissue cultures, and isolated cardenolides may thus be used to elucidate the biosynthesis of cardenolides in the Scrophulariaceae. Therefore...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2006-957937

    authors: Schaller F,Kreis W

    更新日期:1996-10-01 00:00:00

  • Smooth muscle relaxing activity of gentiopicroside isolated from Gentiana spathacea.

    abstract::Bioassay directed fractionation of the (1:1) chloroform-methanol extract of Gentiana spathacea H.B.K (Gentianaceae) led to the isolation of gentiopicroside (gentiopricrin) (1), the major spasmolytic component of the plant. Gentiopicroside inhibited, in a concentration-dependent manner, the spontaneous contractions of ...

    journal_title:Planta medica

    pub_type: 信件

    doi:10.1055/s-2000-9774

    authors: Rojas A,Bah M,Rojas JI,Gutiérrez DM

    更新日期:2000-12-01 00:00:00

  • [Formation of allicin from dried garlic (Allium sativum): a simple HPTLC method for simultaneous determination of allicin and ajoene in dried garlic and garlic preparations].

    abstract::In garlic (Allium sativum L.) the enzyme alliin lyase catalyzes the cleavage of alliin into allicin which reacts further to furnish ajoene. A simultaneous determination of allicin and ajoene is introduced which, in contrast to the determination of alliin only, allows for the testing of the activity of alliin lyase. It...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2006-960120

    authors: Blania G,Spangenberg B

    更新日期:1991-08-01 00:00:00

  • Andrographolide inhibits human hepatoma-derived Hep3B cell growth through the activation of c-Jun N-terminal kinase.

    abstract::Andrographolide (Andro) is a potentially anti-inflammatory diterpenoid lactone isolated from the traditional herbal medicine ANDROGRAPHIS PANICULATA, which has been effectively used for the treatment of infection, inflammation, cold, fever and diarrhea in China for centuries. In the current study, we found that Andro ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-990230

    authors: Ji L,Liu T,Liu J,Chen Y,Wang Z

    更新日期:2007-10-01 00:00:00

  • Variability in yield and composition of essential oil in Cymbopogon jawarancusa.

    abstract::Variability in the oil content in natural populations of Cymbopogon jawarancusa is discussed. Races rich in piperitone, phellandrene and other chemical constituents have been identified. The oil producing ability was largely genetic and showed heritability of 79.0 percent. ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-971731

    authors: Dhar AK,Thappa RK,Atal CK

    更新日期:1981-04-01 00:00:00

  • Chemical and Biological Aspects of Marine Sponges from the Family Mycalidae.

    abstract::Sponges are a useful source of bioactive natural products. Members of the family Mycalidae, in particular, have provided a variety of chemical structures including alkaloids, polyketides, terpene endoperoxides, peptides, and lipids. This review highlights the compounds isolated from Mycalid sponges and their associate...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-0042-103245

    authors: Habener LJ,Hooper JN,Carroll AR

    更新日期:2016-06-01 00:00:00

  • Modified Aloe barbadensis polysaccharide with immunoregulatory activity.

    abstract::Aloe barbadensis polysaccharide was partially digested with cellulase and further purified by dialysis, stepwise ethanol precipitation, and size exclusion chromatography. Crude modified Aloe polysaccharide (MAP) activated macrophage cells and stimulated fibroblast growth. Under the same conditions, native Aloe barbade...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2000-11125

    authors: Qiu Z,Jones K,Wylie M,Jia Q,Orndorff S

    更新日期:2000-03-01 00:00:00

  • Inhibition of platelet aggregation by shikonin derivatives isolated from Arnebia euchroma.

    abstract::Four antiplatelet components were isolated from Arnebia euchroma. They inhibited the aggregation of washed rabbit platelets caused by collagen, arachidonic acid, platelet-activating factor, ADP, or thrombin. The potency of inhibiting collagen-induced platelet aggregation is in the following order: acetylshikonin (IC50...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2006-959718

    authors: Chang YS,Kuo SC,Weng SH,Jan SC,Ko FN,Teng CM

    更新日期:1993-10-01 00:00:00

  • New oligospirostanosides and oligofurostanosides from Asparagus adscendens roots.

    abstract::The methanol extract of the defatted roots of Asparagus adscendens Roxb. yielded beta-sitosterol beta-D-glucoside, two new spirostanol glycosides (asparanin C and asparanin D) and two new furostanol glycosides (asparoside C and asparoside D). ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2007-970018

    authors: Sharma SC,Chand R,Bhatti BS,Sati OP

    更新日期:1982-09-01 00:00:00

  • Genetic characterization and authentication of Embelia ribes using RAPD-PCR and SCAR marker.

    abstract::Embelia ribes Burm. f. (Myrsinaceae) is one of the important plants used in Indian traditional medicine. RAPD-PCR analysis was performed to obtain species-specific DNA fragments. A band of 906 bp that was specific to Embelia ribes irrespective of the geographical source was obtained using the random decamer primer OPF...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2008-1034279

    authors: Devaiah KM,Venkatasubramanian P

    更新日期:2008-02-01 00:00:00

  • Arbuscular mycorrhizal inoculation enhances survival rates and growth of Micropropagated plantlets of Echinacea pallida.

    abstract::In an attempt to induce positive effects on the acclimatization of in vitro propagated Echinacea pallida, four arbuscular mycorrhizal (AM) fungi, Glomus mosseae, Gigaspora ramisporophora, Scutellospora fulgida and Entrophospora colombiana were selected to aid the soil adaptation process. Fungal inocula affected the su...

    journal_title:Planta medica

    pub_type: 信件

    doi:10.1055/s-2003-41124

    authors: Lata H,De Andrade Z,Schaneberg B,Bedir E,Khan I,Moraes R

    更新日期:2003-07-01 00:00:00

  • Isoliquiritigenin inhibits cell proliferation and induces apoptosis in human hepatoma cells.

    abstract::Isoliquiritigenin (4,2',4'-trihydroxychalcone, ISL) is a natural pigment with a simple chalcone structure. In this study, we report the ISL-induced inhibition on the growth of human hepatoma cells (Hep G2) for the first time. The cell growth inhibition achieved by ISL treatment resulted in programmed cell death in a c...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2005-837779

    authors: Hsu YL,Kuo PL,Lin LT,Lin CC

    更新日期:2005-02-01 00:00:00

  • Cytochrome C release induces apoptosis of nasopharyngeal carcinoma (NPC) by antitumor glyfoline.

    abstract::The mechanism of action, leakage of cytochrome c from mitochondria into cytosol, for the antineoplastic compound glyfoline was examined. Additionally, our current studies revealed that glyfoline induced apoptotic changes and arrested cell cycle procession at the G2/M phase in nasopharyngeal carcinoma (NPC). A reverse ...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/s-2005-837747

    authors: Su TL,Huang HM,Wang CK,Wu HC,Lin CT

    更新日期:2005-01-01 00:00:00

  • Single-Lab Validation for Determination of Kavalactones and Flavokavains in Piper methysticum (Kava).

    abstract::Piper methysticum (Kava) is a plant whose roots are used in the preparation of traditional beverages with spiritual, medicinal, and social importance for the Pacific Islanders. Kava is also sold as a herbal supplement or recreational beverage consumed for its mild inebriating effect in Europe and North America. With a...

    journal_title:Planta medica

    pub_type: 杂志文章

    doi:10.1055/a-0637-2400

    authors: Liu Y,Lund JA,Murch SJ,Brown PN

    更新日期:2018-11-01 00:00:00