Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets
Abstract
:1. Introduction
2. Growing Use of Naturally Derived Products
3. Cancer, the Unmet Medical Need
4. Cancer Prevention
5. Alternate Approaches to Malignant Disease
6. Potential of Dietary Phytochemicals for Malignant Disease
6.1. Dietary Polyphenols as Principal Phytochemicals for Malignant Disease
6.2. General Properties of Polyphenols and Evidence on Health
6.2.1. General Pharmacodynamic (or Nutridynamic) Effects of Polyphenols
6.2.2. General Pharmacokinetic (Or Nutrikinetic) Characteristics of Polyphenols
7. Challenges Associated with Cancer Prevention and Dietary Polyphenols
8. Polyphenols of Flaxseed as Important Phytochemicals in Malignant Disease
8.1. Lignans of Flaxseed
8.2. Chemistry and Pharmacokinetics (or Nutrikinetics) of Lignans
8.3. Lignans as Therapeutic Agents for Cancer
8.4. Linking Benefits of Flaxseed with Cancer Associated Chronic Diseases
8.5. Purposing Lignans into Established Models of Cancer Characteristics
8.6. The Multitarget Effects of Lignans in Cancer (Nutridynamics)
8.6.1. Antioxidant and Anti-Inflammatory Properties
8.6.2. Anticarcinogenic and Antimutagenic Properties
8.6.3. Anti-proliferative properties
8.6.4. Dysregulated cellular metabolism
8.6.5. Antiangiogenic Properties
8.6.6. Anti-invasive and Antimigratory Properties
8.6.7. Induction of Apoptosis and Cell Death
9. Final Remarks
10. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
Apc-Min | Mouse tumor model (intestinal and mammary) |
AKT1 | AKT (RAC-alpha) serine/threonine kinase 1 |
ASECO | Anhydro-secoisolariciresinol |
Bax | Bcl-2-associated X protein |
BC | Breast cancer |
Biphasic | ↑lower/↓higher concentration |
CC | Cervical Cancer |
TR | Transfected |
COC | Colon cancer |
ALP | alkaline phosphatase |
miR | micro RNA |
ERK | Extracellular signal–regulated kinases |
subG1 | DNA profile representing cells in the G1 stage of the cell cycle |
F-actin | Filamentous actin |
BIRC5 | Survivin |
BRCA1 | breast cancer type 1 (BCT1) susceptibility protein |
BRCA2 | BCT2 susceptibility protein |
CCNB1 | Cyclin B1 |
CCNB2 | Cyclin B2 |
CCND2 | Cyclin D2 |
CCNF | Cyclin F |
CCNG1 | Cyclin G1 |
CCNH | Cyclin H |
CDC2 | Cell division cycle 2 |
CDC20 | Cell division cycle 20 |
CDK2 | Cyclin dependent kinase 2 |
CDK4 | Cyclin dependent kinase 4 |
CDK5R1 | CDK5 regulatory subunit 1 |
CDKN1B | Cyclin dependent kinase inhibitor 1B/p27/Kip1 |
CDKN3 | Cyclin dependent inhibitor 3/Cip2 |
CDT1 | DNA replication factor Cdt1 |
CHEK1 | CHK1 checkpoint homolog |
CKS1B | CDC28 protein kinase regulatory subunit 1B |
CKS2 | CDC28 protein kinase regulatory subunit 2 |
COX1/2 | Cyclooxygenase 1 & 2 |
CRP | C-reactive protein |
CYP | Cytochrome P450 |
DDX11 | DEAD/H box polypeptide 11 |
DNMT | DNA methyl transferases E2F1, Retinoblastoma protein transcription factor |
F4/80 (EMR1) | EGF-like module-containing mucin-like hormone receptor-like 1 |
GADD45A | Growth arrest and DNA-damage-inducible, alpha |
GMNN | Geminin |
GPER | G protein-coupled estrogen receptor 1 |
HDACs | Histone deacetylases |
HPV | Human papillomavirus |
ITGA2 | Integrin subunit alpha 2 |
KLK3 | Prostate-specific antigen (PSA)/kallikrein-3 |
KLK4 | Kallikrein 4 |
KNTC1 | Kinetochore associated 1 |
KPNA2 | Karyopherin alpha 2 |
LIV-1 | Zinc transporter SLC39A6 |
MAD2L1 | MAD2 mitotic arrest deficient-like 1 |
MBD2 | Methyl-CpG-Binding domain protein |
MCM2 | Mini-chromosome maintenance 2/mitotin |
MCM2/7 | Mini-chromosome maintenance complex component 2/7 |
MCM3 | Mini-chromosome maintenance 3 |
MCM4 | Mini-chromosome maintenance 4 |
MCM5 | Mini-chromosome maintenance 5 |
MCM2/7 | Mini-chromosome maintenance complex component 2/7 |
MKI67 | Antigen identified by mAb Ki-67 |
MBD2 | Methyl-CpG-Binding domain protein |
MO | Mouse orthotopic |
MRE11A | Meiotic recombination 11 homolog A |
16/2-OHE1 | 16/2-hydroxyestrone |
OVX | Ovariectomized rat |
p21 (p21WAF1/Cip1) | Cyclin-dependent kinase inhibitor 1 (CDK-interacting protein 1) |
P53 | Tumor protein p53 (aka “guardian of the genome”) |
p65 | Transcription factor p65 (nuclear factor NF-kappa-B p65 subunit) |
p70S6K1 | Ribosomal protein S6 kinase beta-1 (S6K1)/p70S6 kinase 1 |
PARP | poly-ADP ribose polymerase |
PC | Prostate cancer |
PCNA | Proliferating cell nuclear antigen |
PDGF | Platelet-derived growth factor |
PH | Prostatic hyperplasia |
PIAS1 | E3 SUMO-protein ligase PIAS1 |
PRKCD | Protein kinase C delta type |
PRKCH | Protein kinase C eta type |
Prostaglandin E2 | Dinoprostone |
PS | Prostate Stromal |
pS2 (TFF1) | Trefoil factor family 1 |
RASSF1 | Ras association domain-containing protein 1 |
RBL1 | Retinoblastoma-like 1/p107 |
RPA3 | Replication protein A3 |
SKP2 | S-phase kinase-associated protein |
SLC43A1 | Large neutral amino acid transporter small subunit 3 |
TPM1 | Tropomyosin alpha-1 |
VEGFR | Vascular endothelial growth factor receptor |
XM | Xenograft model |
YAMC | Young adult mouse colon |
ZIP2 | Zinc transporter SLC39A2 |
ZnT-1 | Zinc transporter protein 1 |
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Classification | Representative Members | Examples of Dietary Sources | ||
---|---|---|---|---|
Poly-Phenolics | Phenolic Acids | Hydroxycinnamic acids | p-Coumaric, caffeic, ferulic, sinapic | Barley, eucalyptus, coffee, Arabidopsis, Hibiscus, cereal grains |
Hydroxybenzoic acids | Gallic, vanillic, syringic, ellagic | Chestnuts (boiled or roasted), witch hazel, tea leaves, oak bark, rhubarb, pomegranate, grapes, chocolate, wine | ||
Lignans | Plant Lignans | sesamin, secoisolariciresinol diglucoside, lariciresinol, isolariciresinol, 7-hydroxymatairesinol, matairesinol, pinoresinol, arctigenin, syringaresinol, asarinin | Flaxseed, pumpkin, sunflower, poppy, rye, oats, barley, wheat, oat, rye, berries | |
Mammalian Lignans (enterolignans) | Enterodiol, enterolactone | |||
Stilbenes | Grapes | |||
Other Phenolics | Coumarins | Tonka bean, vanilla grass | ||
Tannins | Eucalyptus, geranium | |||
Flavonoids | Flavonols | Quercetin, kaempferol, myricetin | Aloe Vera, European elderberry, soy, St John’s wort, tomatoes, red onions | |
Flavones | Apigenin, luteolin | Celery, parsley, chamomile tea, green peppers, thyme, oregano | ||
Flavanols (catechins) | Catechin, epicatechin, epigallocatechin gallate | White tea, green tea, persimmon, pomegranate, cocoa beans | ||
Flavanones | Eriodictyol, hesperetin | Citrus fruits, rose hip, mountain balm | ||
Anthocyanidins | Cyanidin, pelargonidin, malvidin | Grapes, berries, red cabbage, red onions, plums, kidney beans, geranium | ||
Isoflavonoids | Genistein, glycitein | Lupin, fava beans, soy, coffee | ||
Alkaloids | Poppy, tomatoes, potatoes | |||
Carotenoids | α-carotene, β-carotene, lutein, zeaxanthin, lycopene | Carrots, broccoli, spinach, zucchini | ||
Organosulfur compounds | Isothiocyanates, indoles, allyl sulfur compounds | Cabbage, broccoli, spinach, garlic, onions |
Experimental System and Lignan * | Targets: Molecules (Protein/Gene) | Block’s Model | Hanahan and Weinberg’s Model | Vogelstein et al., Model |
---|---|---|---|---|
MDA-MB231 (BC) ENL * | ↓Ki67, ↓PCNA, ↓FoxM1, ↓Cyclin E1, ↓Cyclin A2, ↓Cyclin B1 ↓Cyclin B2 [627] | Proliferation, Immortality, Treatment resistance | Sustaining proliferative signaling, Evading growth suppressors | Cell survival |
↓pFAK, ↓pPaxillin [627] ↓ERK-1/2, ↓NF-κB, ↓MAPK-p38, ↓CD44 [647] | Proliferation, Metastasis, Cell-to-cell communication and Immortality | Activating invasion & metastasis, Sustaining proliferative signaling | Cell survival, Cell fate | |
↓uPA, ↓MMP-2, ↓MMP-9, ↑PAI-1, ↑TIMP-1, ↑TIMP-2 [643] ↓N-cadherin, ↓vimentin, ↑E-cadherin, ↑occludin, ↓Snail [647] | Differentiation, Metastasis | Activating invasion & metastasis | Cell fate | |
XM (MDA-MB231) SDG * | ↑LIV-1, ↑↓ ZIP2, ZnT-1 [648] | Proliferation | Sustaining proliferative signaling | Cell survival |
MO (basal-like BC) SDG * | ↓Proinflammatory markers (F4/80, CRP), ↓p-p65 [649] | Inflammation | Tumor promoting inflammation | Cell survival |
MO (MCF7) (BC) ENL * | ↓VEGF, ↑PIGF [331] | Proliferation, Treatment resistance, Angiogenesis | Inducing angiogenesis | Cell survival |
OVX MO (MCF-7) SDG * | ↓ERα, ↓ERβ, ↓EGFR, ↓pS2, ↓IGF-1R, ↓BCL2 [341] | Apoptosis, Proliferation, Glycemia | Sustaining proliferative signaling, Resisting cell death | Cell survival |
↓pMAPK [341] | Proliferation | Sustaining proliferative signaling | Cell survival | |
MCF7, MDA-MB231 ENL * | ↓MMP2, ↓MMP9 ↓MMP14, ± MMP11 [642] | Differentiation, Metastasis | Activating invasion & metastasis | Cell fate |
A549, H60 (Lung cancer) ENL * | ↓pFAK, ↓pSrc, ↓pPaxillin [628] | Proliferation, Metastasis, Cell-to-cell communication | Activating invasion & metastasis, Sustaining proliferative signaling | Cell survival, Cell fate |
↓RhoA, ↓Rac1, ↓Cdc42 [628] | Metastasis, Cell-to-cell communication | Activating invasion & metastasis | Cell fate | |
↑↓FAK, PDGF signaling (AKT1, CCND3). ↓RhoA, Rac1, Cdc42, ↑ITGA2 [628] | Metastasis, Differentiation, Proliferation, Cell-to-cell communication | Activating invasion & metastasis, Sustaining proliferative signaling | Cell survival, Cell fate | |
MG-63 (Osteosarcoma) ENL and ED * | Biphasic (↑↓) – osteonectin, collagen I [650] | Proliferation, Differentiation, Cell-to-cell communication | Activating invasion & metastasis | Cell fate |
↑ALP, ↑osteopontin, ↑osteocalcin [650] | Proliferation, Differentiation, Metastasis, Cell-to-cell communication | Activating invasion & metastasis | Cell fate | |
WPMY-1 (PS) ENL * | ↑GPER, ↑p-ERK, ↑P53, ↑P21, ↓Cyclin D1 [651] | Proliferation, Immortality | Sustaining proliferative signaling | Cell survival |
Rat prostate SDG * | ↑GPER [651] | Proliferation, Immortality | Sustaining proliferative signaling | Cell survival |
WPE1-NA22, WPE1-NB14, WPE1-NB11, WPE1-NB26 and LNCaP (PC) ENL * | ↑↓DNA licensing genes (GMNN, CDT1, MCM2, MCM7) [593] | Proliferation, Immortality, Treatment resistance | Sustaining proliferative signaling | Cell survival, Genome maintenance |
↓miR-106b cluster (miR-106b, miR-93, miR-25),↑PTEN [593] | Proliferation, Angiogenesis | Sustaining proliferative signaling | Cell survival | |
LNCaP ENL * | ↓BRCA1, ↓CDK2, ↓CDKN3, ↓E2F1, ↓KLK3, ↓KLK4, ↓PCNA, ↓PIAS1, ↓PRKCD, ↓PRKCH, ↓RASSF1, ↓TPM1, ↓SLC43A1 [335] | Proliferation, Immortality, Differentiation, Treatment resistance | Sustaining proliferative signaling, Replicative immortality, Evading growth suppressors | Cell survival, Genome maintenance Cell fate |
↓BIRC5, ↓BRCA1, ↓BRCA2, ↓CCNB1, ↓CCNB2, ↓CCNF, ↓CCNG1, ↓CCNH, ↓CDC2, ↓CDC20, ↓CDK2, ↓CDK4, ↓CDK5R1, ↓CDKN1B, ↓CDKN3, ↓CHEK1, CKS1B, ↓CKS2, ↓DDX11, ↓GADD45A, ↓KNTC1, ↓KPNA2, ↓MAD2L1, ↓MCM2, ↓MCM3, ↓MCM4, ↓MCM5, ↓MKI67, ↓MRE11A, ↓PCNA, ↓RBL1, ↓RPA3, ↓SKP2, ↑CCND2 [335] | Proliferation, Immortality, Treatment resistance, Stress chemistry | Sustaining proliferative signaling, Evading growth suppressors | Genome maintenance, Cell survival | |
LNCaP MAT * | ↓pAKT [629] | Treatment resistance, Apoptosis, Proliferation, Glycemia | Sustaining proliferative signaling | Cell survival |
↓DR4 [629] | Apoptosis, Proliferation, Immortality | Resisting cell death | Cell survival, Cell fate | |
↓TRAIL-DISC proteins (c-FLIPL/S, caspase-8) [629] | Apoptosis, Proliferation | Sustaining proliferative signaling, Resisting cell death | Cell survival, Cell fate | |
↑TRAIL-induced BID cleavage [629] | Apoptosis, Proliferation | Resisting cell death | Cell survival | |
LNCaP ENL * | ↑Cytochrome c release, ↑cleaved caspase-3, ↑PARP [634] | Apoptosis, Proliferation, Glycemia, Immortality, Oxidation | Deregulated cellular energetics, and Genome instability and mutation | Cell survival |
↓pAKT, ↓pGSK-3β, ↓pMDM2, ↑P53 [634] | Apoptosis, Immortality, Proliferation | Sustaining proliferative signaling, Evading growth suppressors, Enabling replicative immortality | Cell survival | |
↑Caspase cell death [634] | Apoptosis | Resisting cell death | Cell survival | |
PC3 (PC) ENL * | ↓pIGF-R(IGF-1), ↓pAKT, ↓p-p70S6K1, ↓pGSK3β, ↓pCyclinD1, ↓pERK ½ [618] | Proliferation, Glycemia, Immortality | Sustaining proliferative signaling, Activating invasion & metastasis | Cell survival, Cell fate |
↓IGF-1 signaling [618] | Proliferation, Glycemia | Sustaining proliferative signaling | Cell survival, Cell fate | |
↓FASN [213] | Proliferation, Treatment resistance | Sustaining proliferative signaling, Deregulated cellular energetics | Cell survival | |
HUVEC (endothelial) ENL * | ↓VEGFR-2 [331] | Proliferation, Angiogenesis | Inducing angiogenesis | Cell survival |
Adipocytes ENL * | ↓ROS - oxidative damage, ↓DNMTs, ↓HDACs, ↓MBD2 [334] | Proliferation, Oxidation, Inflammation, Stress chemistry, Immortality | Cell fate, Genome maintenance | |
Colonocytes-YAMC ENL and ED * | ↓Cyclin D1, ↓Bcl-2 [586] | Proliferation, Immortality, Apoptosis | Sustaining proliferative signaling, Resisting cell death | Cell survival |
Colo201 (COC) ENL * | ↓Bcl-2, ↓PCNA, ↑cleaved caspase-3 [22] | Apoptosis, Proliferation | Resisting cell death | Cell survival |
Apc-Min (intestinal) Diet (flaxseed) * | ↓COX-1, COX-2 [652] | Proliferation, Immortality, Inflammation | Sustaining proliferative signaling, Tumor promoting inflammation | Cell survival |
Hens Flaxseed supplement * | ↓COX-2 [583] | Proliferation, Immortality, Inflammation | Tumor promoting inflammation | Cell survival |
↓Prostaglandin E2, ↓ERα, ↓CYP3A4, ↓CYP1B1, ↓16-OHE1, ↑CYP1A1, ↑2-OHE1 [583] | Proliferation, Inflammation, Treatment resistance, Stress chemistry | Tumor promoting inflammation | Cell survival | |
Hela (CC) ENL * | ↓Viral oncogene E6 [588] | Proliferation | Evading growth suppressors | Cell survival |
↓Survivin [588] | Apoptosis, Proliferation | Resisting cell death, Sustaining proliferative signaling | Cell survival | |
↑pHistone H2AX [588] | Apoptosis, Immortality, Proliferation | Resisting cell death | Cell survival, Cell fate | |
Hela ED * | ↑Caspase 3 [588] | Apoptosis | Resisting cell death | Cell survival |
CaSki (CC) ENL * | ↓Viral oncogene E7 [588] | Proliferation | Evading growth suppressors | Cell survival |
↓Bcl-2 [588] | Apoptosis, Treatment resistance | Resisting cell death | Cell survival | |
Hela and CaSki ENL * | ↑P53 [588] | Proliferation, Apoptosis | Evading growth suppressors | Cell survival, Genome maintenance |
↑Bax [588] | Apoptosis, Treatment resistance | Resisting cell death | Cell survival | |
Targets: Cellular Processors | ||||
SKBR3 and MDA-MB231 (BC) ENL * | ↓Cell viability with anticancer agents [55,608] | Proliferation, Treatment resistance, Stress chemistry, Apoptosis | Resisting cell death, Sustaining proliferative signaling, Evading growth suppressors | Cell survival |
MDA-MB231 ENL * | ↑Cell cycle S phase, ↓cell viability [627] | Apoptosis, Immortality, Proliferation | Sustaining proliferative signaling, Evading growth suppressors | Cell survival, Genome maintenance, Cell fate |
↓Actin cytoskeleton organization [627,647] ↓Epithelial–mesenchymal transition [647] | Proliferation, Metastasis | Sustaining proliferative signaling, Activating invasion & metastasis | Cell survival, Cell fate | |
↓Migration, invasion [627,642] | Metastasis | Activating invasion & metastasis | Cell fate | |
↓Actin, filopodia, lamellipodia [642] | Proliferation, Metastasis | Sustaining proliferative signaling, Activating invasion & metastasis | Cell survival, Cell fate | |
Anticancer/metastatic/ proliferative/migratory/clonogenic [643] | Metastasis | Activating invasion & metastasis | Cell fate | |
MCF7 and MDA-MB231 SDG and ASECO * | ↓Growth [653] | Proliferation | Sustaining proliferative signaling | Cell survival |
ER+ BC (XM) ENL and ED * | ↓Angiogenesis [451] | Angiogenesis | Inducing angiogenesis | Cell survival |
WPMY-1 ENL * | ↓proliferation, arrested cell cycle (G0/G1) [651] | Proliferation | Sustaining proliferative signaling | Cell survival |
Rat model (PH) SDG * | ↓Prostate enlargement, # papillary projections, thickness of cell layers [651] | Proliferation | Sustaining proliferative signaling | Cell survival |
WPE1-NA22, WPE1-NB14, WPE1-NB11, WPE1-NB26 and LNCaP ENL * | ↓Metabolic activity,↑doubling time [593] | Proliferation, Stress chemistry, Oxidation | Sustaining proliferative signaling, Deregulated cellular energetics, Evading growth suppressors | Cell survival, Cell fate |
Modulated cell cycle [593] | Proliferation, Immortality | Evading growth suppressors, Sustaining proliferative signaling | Cell survival, Genome maintenance | |
↑Apoptosis [593] | Immortality, Apoptosis | Sustaining proliferative signaling, Resisting cell death | Cell survival | |
LNCaP ENL * | ↑Sub-G0 and S, ↓G0/G1, ↓G2/M cell cycle [335] | Proliferation, Immortality | Sustaining proliferative signaling, Evading growth suppressors | Cell survival, Cell fate |
↓Cell density, ↓metabolic activity, ↓PSA, ↑apoptosis [335] | Proliferation, Apoptosis | Sustaining proliferative signaling, Resisting cell death, Deregulated cellular energetics | Cell survival, Cell fate | |
↑Apoptosis with anticancer agents [335] | Apoptosis | Resisting cell death | Cell survival | |
↓Mitochondrial membrane potential [634] | Treatment resistance, Stress chemistry, Glycemia, Oxidation, Proliferation, Apoptosis | Deregulated cellular energetics | Cell survival | |
LNCaP MAT * | Death receptor sensitizer (sensitizes TRAIL-induced apoptosis) [629] | Proliferation, Apoptosis | Sustaining proliferative signaling, Evading growth suppressors, Resisting cell death | Cell survival, Cell fate |
↑TRAIL-induced mitochondrial depolarization [629] | Proliferation, Apoptosis | Resisting cell death, Deregulated cellular energetics | Cell survival | |
PC3 ENL * | ↓IGF-1 induced proliferation, ↓cell cycle arrest (G0/G1) [618] | Proliferation | Sustaining proliferative signaling, Evading growth suppressors | Cell survival |
↓IGF-1 induced migration [618] | Metastasis | Activating invasion & metastasis | Cell survival, Cell fate | |
A549 and H60 ENL * | ↓Migration, invasion [628] | Metastasis | Activating invasion & metastasis | Cell fate |
↓Density F-actin fibers [628] | Metastasis, Proliferation | Activating invasion & metastasis, Sustaining proliferative signaling | Cell survival, Cell fate | |
YAMC ENL and ED * | ↓Cell growth, ↑ apoptosis [586] | Proliferation, Apoptosis | Resisting cell death, Sustaining proliferative signaling, Evading growth suppressors | Cell survival |
MG-63 ENL and ED * | Biphasic (↓↑)- cell viability, ALP activity [650] | Proliferation | Sustaining proliferative signaling | Cell survival, Cell fate |
Mouse model ENL * | ↓Estradiol-induced endothelial cell infiltration [331] | Metastasis | Activating invasion & metastasis | Cell survival, Cell fate |
Colo201 ENL * | ↑Apoptosis (sub-G1 cells),↑cell viability [22] | Proliferation, Apoptosis | Sustaining proliferative signaling, Evading growth suppressors, Resisting cell death | Cell survival |
CC cells ENL * | ↑Cell death, ↓ metabolic activity in p53+ [588] | Immortality, Proliferation, Treatment resistance, Glycemia, Apoptosis | Evading growth suppressors, Resisting cell death, Deregulated cellular energetics | Cell survival, Genome maintenance |
↑Apoptosis (Hela) [588] | Apoptosis | Resisting cell death | Cell survival | |
CC cells ENL and ED * | ↓Cell survival [588] | Immortality, Proliferation, Apoptosis | Sustaining proliferative signaling, Evading growth suppressors | Cell survival, Genome maintenance |
TR C33-A (CC) ENL and ED * | ↓Promoter activity (Episomal, HPV oncoproteins) [588] | Proliferation | Sustaining proliferative signaling, Evading growth suppressors | Cell survival |
Hela ENL * | ↑p53 activity [588] | Immortality, Proliferation | Evading growth suppressors | Cell survival, Genome maintenance |
No DNA-breaks (genotoxicity) [588] | Proliferation, Apoptosis | Resisting cell death, Evading growth suppressors | Cell survival | |
Hela/CaSki ENL * | ↑Apoptosis (Caspase 9, Caspase 3) [588] | Proliferation, Apoptosis | Resisting cell death | Cell survival |
CaSki ED * | ↑Caspase 3 activity [588] | Proliferation, Apoptosis | Resisting cell death | Cell survival |
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
De Silva, S.F.; Alcorn, J. Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets. Pharmaceuticals 2019, 12, 68. https://doi.org/10.3390/ph12020068
De Silva SF, Alcorn J. Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets. Pharmaceuticals. 2019; 12(2):68. https://doi.org/10.3390/ph12020068
Chicago/Turabian StyleDe Silva, S. Franklyn, and Jane Alcorn. 2019. "Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets" Pharmaceuticals 12, no. 2: 68. https://doi.org/10.3390/ph12020068
APA StyleDe Silva, S. F., & Alcorn, J. (2019). Flaxseed Lignans as Important Dietary Polyphenols for Cancer Prevention and Treatment: Chemistry, Pharmacokinetics, and Molecular Targets. Pharmaceuticals, 12(2), 68. https://doi.org/10.3390/ph12020068