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Table 2 List of selected genes regulated by black cohosh extract in MCF-7 cells. Genes are listed with symbol, GenBank accession number and fold changes vs. DMSO control of two independent microarray experiments. Genes in bold are associated to stress response. Those written in italics have been verified by real-time RT-PCR. A full list with all 431 genes is available [see Additional file 1].

From: Gene expression profiling reveals effects of Cimicifuga racemosa (L.) NUTT. (black cohosh) on the estrogen receptor positive human breast cancer cell line MCF-7

Gene Title

Gene Symbol

Accession No.

Fold Change

   

#1

#2

APOPTOSIS

DNA-damage-inducible transcript 4

DDIT4

NM_019058

5.1

5.6

P8 protein (candidate of metastasis 1)

P8

AF135266

4.4

2.7

Tumor protein p53 inducible nuclear protein 1

TP53INP1

AW341649

3.5

3.1

Tumor necrosis factor receptor superfamily, member 10b

TNFRSF10B

AF016266

2.5

2.7

Immediate early response 3

IER3

NM_003897

2.0

1.9

BCL2/adenovirus E1B 19 kda interacting protein 3-like

BNIP3L

AL132665

1.8

1.6

Helicase, lymphoid-specific

HELLS

AI650364

-2.8

-2.7

Baculoviral IAP repeat-containing 5 (survivin)

BIRC5

AA648913

-3.1

-2.0

PROLIFERATION

Cell cycle/Proliferation

    

Growth differentiation factor 15

GDF15

AF003934

6.0

4.5

Vascular endothelial growth factor

VEGF

AF022375

4.6

4.2

Cyclin G2

CCNG2

AW134535

2.8

2.3

DNA-damage-inducible transcript 3 (CHOP-10, GADD153)

DDIT3

BC003637

2.6

2.7

RAS, dexamethasone-induced 1

RASD1

AF069506

2.6

2.4

Sestrin 2

SESN2

BF131886

2.4

2.8

Growth arrest and DNA-damage-inducible, alpha

GADD45A

NM_001924

2.2

2.6

Cyclin-dependent kinase inhibitor 1A (p21, Cip1)

CDKN1A

NM_000389

1.8

1.6

Forkhead box O3A

FOXO3A

AV725666

1.8

1.9

Cyclin B1 interacting protein 1

CCNB1IP1

NM_021178

1.6

1.6

Cyclin-dependent kinase 7

CDK7

L20320

1.6

1.6

Cyclin F

CCNF

U17105

-1.5

-1.9

S-phase kinase-associated protein 2 (p45)

SKP2

BC001441

-1.6

-1.6

Chromatin assembly factor 1, subunit A (p150)

CHAF1A

BF062223

-1.7

-1.6

Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase

PKMYT1

NM_004203

-1.8

-1.6

E2F transcription factor 2

E2F2

AL561296

-2.2

-1.6

Kinetochore protein Spc24

Spc24

AI469788

-2.2

-1.8

Cyclin A2

CCNA2

NM_001237

-2.3

-1.5

Proliferation-related Ki-67 antigen

MKI67

AU152107

-2.3

-1.9

Cyclin E2

CCNE2

AF112857

-2.6

-3.0

E2F transcription factor 7

E2F7

AI341146

-2.7

-2.1

Kinesin family member 11 (Eg5)

KIF11

NM_004523

-2.7

-1.7

DNA replication, repair and synthesis

    

Recq protein-like 4

RECQL4

NM_004260

-1.7

-1.7

Cyclin-dependent kinase 2

CDK2

AB012305

-2.1

-1.5

Minichromosome maintenance deficient 3 (S. Cerevisiae)

MCM3

NM_002388

-2.1

-1.8

CDC6 cell division cycle 6 homolog (S. Cerevisiae)

CDC6

NM_001254

-2.5

-1.6

DNA replication factor

CDT1

AF321125

-2.5

-1.7

BRCA1 interacting protein C-terminal helicase 1

BRIP1

AF360549

-2.6

-1.7

Minichromosome maintenance deficient 5, cell division cycle 46 (S. Cerevisiae)

MCM5

AA807529

-2.6

-1.7

Minichromosome maintenance deficient 7 (S. Cerevisiae)

MCM7

AF279900

-2.7

-1.8

Ubiquitin-like, containing PHD and RING finger domains, 1

UHRF1

AK025578

-2.7

-2.7

Thymidine kinase 1, soluble

TK1

BC007986

-2.8

-1.7

Proliferating cell nuclear antigen

PCNA

NM_002592

-2.9

-1.9

Replication factor C (activator 1) 3, 38 kda

RFC3

NM_002915

-3.0

-1.7

Minichromosome maintenance deficient 2, mitotin (S. Cerevisiae)

MCM2

NM_004526

-3.1

-1.6

DNA replication complex GINS protein PSF2

Pfs2

BC003186

-3.3

-1.5

Flap structure-specific endonuclease 1

FEN1

NM_004111

-3.4

-2.5

Minichromosome maintenance deficient 4 (S. Cerevisiae)

MCM4

AI859865

-3.4

-2.4

Thymidylate synthetase

TYMS

AB077208

-3.4

-2.4

ASF1 anti-silencing function 1 homolog B (S. Cerevisiae)

ASF1B

NM_018154

-3.5

-2.1

GENERAL GROWTH

Protein processing

    

Chromosome 1 open reading frame 24

C1orf24

AF288391

4.9

5.1

Seryl-tRNA synthetase

SARS

AU147785

4.4

4.0

DnaJ (Hsp40) homolog, subfamily C, member 10

DNAJC10

BG168666

3.1

1.9

DnaJ (Hsp40) homolog, subfamily B, member 9

DNAJB9

AL080081

2.9

2.3

Homocysteine-inducible, endoplasmic reticulum stress-inducible, ubiquitin-like domain member 1

HERPUD1

AF217990

2.5

2.0

Tryptophanyl-tRNA synthetase

WARS

NM_004184

2.5

2.2

MAP kinase-interacting serine/threonine kinase 2

MKNK2

NM_017572

2.4

2.0

Eukaryotic translation initiation factor 4E binding protein 1

EIF4EBP1

AB044548

2.3

1.8

Stress 70 protein chaperone, microsome-associated, 60 kda

STCH

NM_006948

2.3

2.7

Eukaryotic translation initiation factor 2-alpha kinase 3 (syn. PERK)

EIF2AK3

NM_004836

2.2

1.7

Methionine-tRNA synthetase

MARS

AA621558

2.2

2.2

Microtubule-associated protein 1 light chain 3 beta

MAP1LC3B

AF183417

2.2

1.9

Tyrosyl-tRNA synthetase

YARS

AW245400

2.0

1.7

Cysteinyl-tRNA synthetase

CARS

AI769685

1.9

2.0

Isoleucine-tRNA synthetase

IARS

NM_013417

1.9

2.0

F-box only protein 11

FBXO11

AL117620

1.9

1.7

Ubiquitin protein ligase E3 component n-recognin 1

UBR1

AV715153

1.9

1.8

Glutamyl-prolyl-tRNA synthetase

EPRS

NM_004446

1.8

1.7

Heat shock 70 kda protein 5 (glucose-regulated protein, 78 kda)

HSPA5

AF216292

1.8

1.6

Transducin (beta)-like 1X-linked

TBL1X

AW968555

1.8

1.9

Ubiquitin specific protease 3

USP3

AF077040

1.8

1.8

Eucaryotic translation initiation factor 1

EIF1

AF083441

1.7

1.7

Glycyl-tRNA synthetase

GARS

D30658

1.7

2.3

SUMO1/sentrin specific protease 6

SENP6

AF306508

1.7

1.6

APG12 autophagy 12-like (S. Cerevisiae)

APG12L

BE965998

1.6

1.7

Ubiquitin-fold modifier 1

Ufm1

NM_016617

1.6

1.6

Heat shock 70 kda protein 2

HSPA2

U56725

-1.7

-1.9

F-box only protein 5 (early mitotic inhibitor 1)

FBXO5

AK026197

-2.0

-1.7

Ubiquitin-conjugating enzyme E2C

UBE2C

NM_007019

-2.0

-1.6

Transcription

    

Basic helix-loop-helix domain containing, class B, 2

BHLHB2

NM_003670

3.6

2.6

Trinucleotide repeat containing 9

TNRC9

AK025084

3.4

2.1

Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2

CITED2

AF109161

3.1

1.5

CCAAT/enhancer binding protein (C/EBP), beta

CEBPB

AL564683

2.4

2.3

CCAAT/enhancer binding protein (C/EBP), gamma

CEBPG

NM_001806

2.2

2.4

Junction-mediating and regulatory protein

JMY

BF447037

2.2

1.6

Endothelial PAS domain protein 1 (Hypoxia-inducible factor 2, alpha)

EPAS1

AF052094

2.1

1.9

Nuclear factor (erythroid-derived 2)-like 2

NFE2L2

NM_006164

2.0

1.5

Activating transcription factor 3

ATF3

NM_001674

1.8

2.0

Activating transcription factor 4

ATF4

NM_001675

1.7

1.5

Early growth response 1

EGR1

AI459194

1.7

4.7

Nuclear factor (erythroid-derived 2)-like 1

NFE2L1

NM_003204

1.6

1.6

Chromobox homolog 4 (Pc class homolog, Drosophila)

CBX4

AI570531

1.5

1.8

Kruppel-like factor 4 (gut)

KLF4

BF514079

1.5

1.8

Zinc finger protein 36, C3H type-like 2

ZFP36L2

AI356398

-3.1

-2.1

Cell organization, adhesion & structure and cytoskeleton

    

Decay accelerating factor for complement (CD55, Cromer blood group system)

DAF

NM_000574

3.6

3.3

Ras homolog gene family, member B

RHOB

AI263909

-1.8

-1.6

SIGNALING AND TRANSPORT

Receptors & Signal transduction

    

Unc-5 homolog B (C. Elegans)

UNC5B

AK022859

3.3

2.1

Stanniocalcin 2

STC2

BC000658

2.6

2.3

TRAF family member-associated NFKB activator

TANK

U59863

2.2

2.3

Interferon gamma receptor 1

IFNGR1

NM_000416

2.1

1.6

Mitogen-inducible gene 6

MIG-6

AL034417

2.1

2.5

Ras association (ralgds/AF-6) domain family 3

RASSF3

AI628605

2.0

1.5

Aryl hydrocarbon receptor

AHR

NM_001621

1.8

1.8

Tribbles homolog 1 (Drosophila

TRIB1

NM_025195

1.7

1.6

Tribbles homolog 3 (Drosophila)

TRIB3

NM_021158

1.7

1.6

Aryl hydrocarbon receptor nuclear translocator-like

ARNTL

AB000815

1.6

1.8

Casein kinase 1, gamma 3

CSNK1G3

NM_004384

1.5

1.6

Hypoxia-inducible factor 1, alpha subunit

HIF1A

NM_001530

1.5

1.5

c-Jun N-terminal kinase 1 (mitogen-activated protein kinase 8, MAPK8)

JNK1

AU152505

1.5

1.5

Tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide

YWHAH

NM_003405

-1.8

-1.9

Estrogen receptor, alpha

ESR1

NM_000125

-2.0

-1.8

Transport

    

Solute carrier family 7, (cationic amino acid transporter, y+ system) member 11

SLC7A11

AA488687

6.2

5.7

Potassium voltage-gated channel, Isk-related family, member 4

KCNE4

AI002715

3.1

2.1

Solute carrier family 7 (cationic amino acid transporter, y+ system), member 5

SLC7A5

AB018009

2.3

2.0

Solute carrier family 38, member 2

SLC38A2

NM_018976

2.0

2.0

Ferritin H

FTH1

AA083483

1.9

1.9

Solute carrier family 1 (glutamate/neutral amino acid transporter), member 4

SLC1A4

AI889380

1.6

1.6

METABOLISM

Oxidoreductase activity

    

Cytochrome P450, family 1, subfamily A, polypeptide 1

CYP1A1

NM_000499

12.4

3.5

Aldo-keto reductase family 1, member C1 (20-alpha (3-alpha)-hydroxysteroid dehydrogenase)

AKR1C1

M33376

5.5

2.3

Aldehyde dehydrogenase 1 family, member L2

ALDH1L2

AI654224

5.0

2.2

Cytochrome P450, family 1, subfamily B, polypeptide 1

CYP1B1

NM_000104

4.1

2.7

Heme oxygenase (decycling) 1

HMOX1

NM_002133

3.3

2.1

Glutaredoxin (thioltransferase)

GLRX

AF162769

3.0

1.9

Sterol-C4-methyl oxidase-like

SC4MOL

AV704962

2.5

2.4

Aspartate beta-hydroxylase

ASPH

AF289489

2.4

2.2

5-Methyltetrahydrofolate-homocysteine methyltransferase reductase

MTRR

NM_024010

2.3

2.2

Methylene tetrahydrofolate dehydrogenase (NAD+ dependent)

MTHFD2

NM_006636

1.9

2.0

Sterol-C5-desaturase

SC5DL

D85181

1.5

1.6

Cytochrome P450, family 51, subfamily A, polypeptide 1 (Sterol 14-alpha-demethylase)

CYP51A1

NM_000786

1.6

1.6

Farnesyl-diphosphate farnesyltransferase 1 (Squalene synthase)

FDFT1

AA872727

1.6

1.7

3-Hydroxy-3-methylglutaryl-Coenzyme A reductase

HMGCR

AL518627

1.8

1.7

Biosynthesis/Catabolism

    

Asparagine synthetase

ASNS

NM_001673

3.7

4.1

Acyl-coa synthetase long-chain family member 1

ACSL1

NM_021122

2.6

2.2

Phosphoenolpyruvate carboxykinase 2 (mitochondrial)

PCK2

NM_004563

2.5

3.3

Spermidine/spermine N1-acetyltransferase

SAT

BE326919

1.6

1.8

OTHERS

Metastasis associated in lung adenocarcinoma transcript 1

MALAT-1

BG534952

11.0

3.1

S100 calcium binding protein P

S100P

NM_005980

5.8

5.1

Gastric-associated differentially-expressed protein YA61P, drug sensitive protein 1

---

AF220415

5.6

2.1

Hypothetical protein LOC222171

LOC222171

AI347918

5.1

3.6

Brain expressed X-linked 2

BEX2

AF251053

4.6

3.6

Myozenin 2 (calcisarcin 1)

MYOZ2

AI475544

4.5

3.8

WD40 repeat protein Interacting with phosphoinositides of 49 kda

WIPI49

AW052084

3.5

2.1

SLIT and NTRK-like family, member 6

SLITRK6

AI680986

3.4

2.4

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BMC Pharmacology

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