Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence
Abstract
:1. Introduction
Source of Data
2. The Connection Between Fat, Gut Microbiota, and Inflammatory Diseases
3. HFD, Oxidative Stress, and Inflammation
4. Xenobiotics in the Obesity-Cancer Link
5. Mediterranean Diet and Cancer Risk
6. Dietary Fat and Cancer Risk
6.1. Total Fat
6.2. Saturated Fat
6.2.1. The Role of SFAs in Signalling Pathways Involved in Cancer
Palmitic Acid
Stearic Acid
Lauric Acid (LaA)
Myristic Acid (MA)
The Impact of Other SFAs on Carcinogenesis
6.3. Unsaturated Fat
6.3.1. MUFAs
6.3.2. PUFAs
Ω-6 PUFAs
Ω-3 PUFAs
Trans Fatty Acids (TFAs)
6.3.3. iTFAs
6.3.4. rTFAs
In Vitro | In Vivo | Human Data | |||||||
---|---|---|---|---|---|---|---|---|---|
Cell Line, Fat Specification | Outcome | Reference | Model, Fat Specification | Outcome | Reference | Cancer Type, Fat Specification | Outcome | Reference | |
SATURATED FAT | |||||||||
All cancers | Positive association between high SFAs intake and cancer risk and mortality, respectively | [123,124] | |||||||
HER2/neu-positive breast cancer cells, PA | Induction of cell cycle delay and apoptosis | [151] | Spontaneous mammary tumours, C3H mice, diet supplemented with PA, SA, MA, and LaA, respectively | No effect of diet supplemented with PA, MA or LaA, respectively | [304] | Breast cancer, high SFAs intake | Positive association | [103,124] | |
Breast cancer, PA and SA intake | Positive association | [154] | |||||||
Hs578T human breast cancer cells, SA | Growth suppression via cell cycle inhibition | [161] | Breast cancer, PA intake | No association | [155] | ||||
NMU-induced mammary tumours, Sprague-Dawley rats, HFD rich in SA | Decreased tumour incidence and increased latency after SA supplementation | [161] | |||||||
SkBr3 breast cancer cells, LaA | Inhibition of proliferation, apoptosis stimulation | [167] | |||||||
MDA-MB-231 breast cancer cells, capric, caprylic and caproic acids | Cell growth inhibition and apoptosis stimulation | [178] | MDA-MB-435 xenografts, athymic mice, HFD rich in SA | Decreased incidence and multiplicity of tumours | [305] | ||||
Spontaneous mammary tumours, A/ST mice, HFD rich in SA | Growth suppression, increased tumour latency | [306] | |||||||
HCT-15 colon cancer cells, LaA | Apoptosis induction | [9] | Azoxymethane-induced colorectal cancer, F344 rats, HFD rich in SFAs | Increased incidence and multiplicity of colon tumours, induction of colonic inflammation | [307] | Colon cancer, SFAs intake | No association | [112] | |
Caco-2 human colon cancer cells, LaA | Suppression of proliferation | [168] | HCT116 colorectal cancer xenografts, nude mice, HFD rich in PA | Tumour growth stimulation | [8] | ||||
CT26 mouse colon cancer cells, LaA | Suppression of proliferation, increase in oxidative stress | [169] | |||||||
HCT-116 colorectal cancer cells, capric, caprylic and caproic acids | Cell growth inhibition, apoptosis stimulation | [178] | |||||||
Hep3B, SW480, SW620, AGS, BGC-823, HGC-27, 97H, and LM3 hepatocarcinoma cells, PA | Reduced cell proliferation, impaired cell invasiveness | [152] | LM3 hepatocarcinoma xenografts, athymic mice, PA (via gavage) | Tumour growth suppression | [152] | ||||
PNT1A and PC3 prostate cancer cell lines, PA | Increased proliferation and migration | [147] | PC-3 prostate cancer xenografts, SCID mice, HFD rich in PA | Stimulated proliferation | [98] | Prostate cancer, SFAs intake | Positive association | [125] | |
Prostate cancer, PA intake | Positive association | [154] | |||||||
Prostate cancer, PA intake | No association | [155] | |||||||
Prostate cancer, MA intake | Positive association | [176] | |||||||
AsPC-1 pancreatic cancer cells, PA | Increased invasiveness | [148] | Nude mice, HPAF pancreatic cancer xenografts, HFD rich in SFAs | Increased tumour viability | [308] | Pancreatic cancer, SFAs intake, PA and SA intake | Negative association | [127] | |
MIA PaCa-2, PANC-1 and CFPAC pancreatic cancer cells, PA, SA, LaA | Growth inhibition | [309] | |||||||
Gastric cancer cell lines, PA | Promotion of metastasis | [150] | |||||||
Oral carcinoma cell lines PA | Increased metastasis | [149] | |||||||
Ovarian cancer, SFAs intake | Positive association | [158] | |||||||
No association | [126] | ||||||||
Ischikawa endometrial cancer cells, LaA | Inhibition of proliferation, apoptosis stimulation | [167] | |||||||
A-431 skin cancer cells, capric, caprylic and caproic acids | Cell growth inhibition, apoptosis stimulation | [178] | |||||||
UNSATURATED FAT | |||||||||
MUFAs | |||||||||
Isocaloric replacement of SFAs with plant MUFAs | Decreased cancer mortality | [123] | |||||||
Isocaloric replacement of animal MUFAs with plant MUFAs | [192] | ||||||||
MCF-7 breast cancer cells, OA | Stimulation of proliferation | [180] | Breast cancer, olive oil consumption, highest vs lowest intake | Decreased risk | [191] | ||||
Suppressed growth and survival | [182] | ||||||||
Increased invasiveness | [184] | ||||||||
MDA-MB-231, OA | Stimulation of growth and migration | [182] | |||||||
Increased invasiveness | [184] | ||||||||
BT-474 and SK-Br3 breast cancer cells, OA | Inhibition of Her-2/neu expression | [181] | |||||||
Caco-2 colon cancer cell line, OA | Growth promotion | [186] | Colon cancer, MUFAs intake | No association | [112] | ||||
SGC 7901gastric carcinoma cells, OA | Suppressed growth and survival | [182] | GIT cancer, MUFAs intake | Decreased risk | [124] | ||||
HGC-27 gastric carcinoma line, OA | Stimulation of growth and migration | [182] | GIT cancer, olive oil consumption, highest vs lowest intake | [191] | |||||
MKN-45 and AGS gastric cancer cell lines, OA | Increased invasiveness | [185] | |||||||
Prostate cancer, MUFAs intake | Positive association | [125] | |||||||
Ovarian cancer, MUFAs intake | No association | [126] | |||||||
HeLa cervical cancer xenografts, BALB/c mice, diet high in OA | Increased growth and metastasis | [188] | |||||||
Basal cell carcinoma, MUFAs intake | Inverse association between intake and risk | [113] | |||||||
786-O renal cancer cells, OA | Increased invasiveness | [187] | |||||||
CAL27 and UM1 tongue squamous cell carcinomas, OA | Induction of apoptosis and autophagy | [189] | |||||||
PUFAs | |||||||||
ω-6 PUFAs | |||||||||
Isocaloric replacement of SFAs with LA | Decrease in cancer mortality | [123] | |||||||
Colon cancer, PUFAs intake | No association | [112] | |||||||
MDA-MB-231 breast cancer cells, LA | Promotion of migration and invasion | [212] | DMBA-induced mammary tumours, Sprague-Dawley rats, diet high in LA | Stimulation of DMBA-DNA adducts formation in mammary gland | [221] | Breast cancer, ω-6 PUFAs intake | No association | [110] | |
Breast cancer, higher dietary ω-3 PUFAs / ω-6 PUFAs ratio | Lower risk in Asian countries | [222] | |||||||
RKO and LOVO colon cancer cell lines, LA | Growth stimulation by low concentrations, grow inhibition by high concentrations | [209] | C57BL/6J mice, diet high in LA | Epigenetic alterations associated with colonic inflammation and cancer | [220] | ||||
SW480 and SW620 colon cancer cells, LA | Decreased cell proliferation and viability | [210] | |||||||
AGS gastric adenocarcinoma cells, LA | Growth inhibition | [211] | CUM-2MD3 gastric carcinoma transplants, NCr-nu/nu mice, HFD rich in LA | Stimulation of invasion and metastasis | [218] | ||||
OCUM-2MD3 gastric carcinoma transplants, athymic nude mice, HFD rich in LA | Enhanced tumour growth and angiogenesis | [219] | |||||||
Oral carcinomas induced by DMBA and betel quid extract, hamsters, high dietary ω-6 PUFAs / ω-3 PUFAs ratio | Tumour growth promotion | [216] | |||||||
MIA PaCa-2, PANC-1 and CFPAC pancreatic cancer cells, LA | Growth inhibition | [309] | HPAF pancreatic cancer xenografts, nude mice, HFD rich in ω-6 PUFAs | Increased tumour viability, stimulation of liver metastasis | [308] | ||||
Pancreatic neoplasia, KRAS transgenic mice, diet high in ω-6 PUFAs | Shortened tumour latency | [217] | |||||||
PC-3 and C4-2 prostatic cancer cells, AA and LA | Reduced cell proliferation and viability | [207] | |||||||
T98G glioblastoma cells, AA | Growth inhibition | [180] | |||||||
ω-3 PUFAs | |||||||||
MCF-7 mammary cancer cells, ALA or ALA combined with EPA and DHA | Decreased viability | [223] | 4T1 mammary tumour transplants, BALB/c mice, ω-3 PUFAs enriched diet | Decrease in proliferation and angiogenesis, stimulation of apoptosis | [243] | Breast cancer, highest ω-3 PUFAs intake vs lowest ω-3 PUFAs intake / high ω-6 PUFAs intake | Decreased risk | [254] | |
MCF-7 cells, DHA | Reduced proliferation | [226] | |||||||
LM3 mammary transplants, BALB/c mice, ALA enriched diet | Inhibition of tumour growth and metastasis | [244] | Breast cancer, fish ω-3 PUFAs intake | Decreased risk in Asian patients | [255] | ||||
MDA-MB-231 cells DHA | Pyroptosis induction | [225] | |||||||
DMBA-induced mammary tumours in offspring of rats fed with diet enriched with ALA or DHA and EPA, respectively, C57BL/6J mice | Tumour growth inhibition, reduced proliferation and stimulation of apoptosis | [245] | |||||||
HT-29 and CaCo-2 colorectal cancer cells, DHA | Decreased viability | [227] | Azoxymethane-induced colorectal cancer, F344 rats, HFD rich in ω-3 PUFAs | Decreased incidence and multiplicity of colon tumours in comparison with HFD rich in SFAs | [307] | Colorectal cancer, long-chained ω-3 PUFAs | Inverse association between intake and risk | [256] | |
HCT-116 and Caco-2 cells, DHA | Anti-angiogenic activity | [228] | |||||||
HCT-116, HT-29, SW620, DLD-1 colorectal cancer cells, DHA | Decreased proliferation, enhancement of autophagy induced by oxaliplatin | [231] | HCT116 xenografts, BALB/c mice, DHA (i.p.) | Enhancement of autophagy induced by oxaliplatin | [231] | ||||
N-methyl phosphite nitrourea-induced colorectal cancer, rats, ω-3 PUFAs enriched diet | Tumour growth inhibition | [246] | |||||||
Colorectal neoplasia, transgenic Apc Min/+mice, dietary fish-oil ω-3 PUFAs | Decreased colorectal carcinoma growth | [247] | |||||||
MC38 colorectal carcinoma, C57BL/6 mice, ω-3 PUFAs enriched diet | Tumour growth suppression | [248] | |||||||
MIA PaCa-2, PANC-1 and CFPAC pancreatic cancer cells, ALA, DHA, EPA | Growth inhibition | [308] | HPAF pancreatic cancer xenografts, nude mice, HFD rich in ω-3 PUFAs | Decreased tumour viability | [309] | ||||
Pancreatic carcinoma, KRAS mice, fish oil ω-3 PUFAs enriched diet | Tumour growth inhibition, reduced proliferation | [249] | |||||||
PANC-1 pancreatic cancer cells, DHA | Apoptosis induction | [232] | |||||||
SW1990, PANC-1 pancreatic cancer cells, EPA, DHA | Growth inhibition | [235] | PANC02 transplants, fat-1 transgenic mice | Tumour growth inhibition, apoptosis induction | [235] | ||||
MHCC 97-L metastatic hepatocarcinoma line | Decreased proliferation, DHA | [236] | |||||||
Prostate carcinoma, Pten-knockout mice, diet enriched with ALA | Tumour growth inhibition | [250] | Prostate cancer risk, ω-3 PUFAs intake | No effect | [258] | ||||
Endometrial cancer xenografts, BALB/c mice, dietary ω-3 PUFAs | Tumour growth inhibition | [251,252] | Breast cancer, long-chain ω-3 PUFAs intake | Decreased risk in women with normal BMI | [257] | ||||
SKOV-3 ovarian cancer line, EPA | Apoptosis induction | [237] | Ovarian cancer, PUFAs intake | No association | [126] | ||||
SKOV3, A2780, HO8910 ovarian cancer cells, ALA, DHA | Decreased viability by ALA and DHA, inhibition of invasion and metastasis by DHA | [238] | |||||||
A549 non-small lung cancer cells, DHA | Inhibition of proliferation | [233,234] | |||||||
LLC murine lung cancer cells, DHA | [234] | ||||||||
LA-N-1 neuroblastoma cells, DHA, EPA | Cell cycle arrest and induction of apoptosis | [239] | GL261 glioma transplants, fat-1 transgenic mice | Induction of apoptosis and autophagy | [240] | ||||
D54MG, U87MG and U251MG glioblastoma cells, DHA | Induction of apoptosis and autophagy | [240] | |||||||
G1a, ML-2, HL-60, THP-1, U937 and MOLM-13 acute myeloid leukaemia cell lines, DHA and EPA | Decrease in cell viability | [241] | |||||||
Molt-4 acute lymphoblastic leukaemia cells, DHA | Apoptosis induction | [242] | |||||||
TFAs | |||||||||
iTFAs | |||||||||
Ehrlich tumour, CBA mice, dietary EA | Tumour growth promotion, decreased survival | [273] | Oestrogen-receptor negative breast cancer risk, serum level of iTFAs | Positive association | [302] | ||||
CT-26 and HT-29 colorectal cancer cells, EA | Enhanced growth and metastasis | [270,271] | Colon cancer risk, TFAs intake | Positive association | [298,299] | ||||
Attenuation of 5-fluorouracil cytotoxicity | [271] | CT26 and HT29 transplants, BALB/c mice, dietary EA | Increased tumour growth and metastasis | [270,272] | Rectal cancer risk, fish TFAs intake | Positive association | [269] | ||
Caco-2 colorectal cancer cells, EA | No effect on growth | [186] | |||||||
CMT93 murine rectal carcinoma cell line, EA | Increased stemness, attenuation of 5-fluorouracil cytotoxicity | [271] | |||||||
Stomach cancer risk, fish TFAs intake | Positive association | [269] | |||||||
Prostate cancer risk, total TFAs intake | Positive association | [125] | |||||||
Prostate cancer risk, fish TFAs intake | Negative association | [269] | |||||||
Pancreatic cancer risk, vegetable TFAs intake | Negative association in men | [269] | |||||||
Pancreatic risk, serum level of iTFAs | Positive association in men | [303] | |||||||
Ovarian cancer risk, TFAs intake | Positive association | [301] | |||||||
SH-SY5Y neuroblastoma cells, EA | Growth inhibition, apoptosis induction | [274] | CNS cancer risk | Negative association in women | [269] | ||||
LL2 murine lung cancer cell line, EA | Increased stemness, attenuation of 5-fluorouracil cytotoxicity | [271] | Lung cancer risk | Negative association in women | [269] | ||||
Non-Hodgkin lymphoma risk, vegetable TFAs intake | Negative association | [269] | |||||||
Multiple myeloma, fish TFAs intake | Positive association | ||||||||
Bladder cancer risk, fish TFAs intake | Negative association | [269] | |||||||
rTFAs | |||||||||
MCF-7 mammary carcinoma, VA | Inhibition of proliferation | [275] | Mammary tumour growth | Growth inhibition | Reviewed in [287] | Breast cancer risk, CLA intake | No association | [297] | |
MCF-10A mammary cancer cells, VA | No effect | [276] | DMBA-induced mammary tumours in Sprague-Dawley rat offspring, maternal diet enriched with CLA | Decreased susceptibility to tumour induction | [291] | Post-menopausal breast cancer, rTFAs intake | Positive association | [269] | |
MCF-7 and MDA-MB-231 cells, CLA | Growth inhibition | [278,281] | |||||||
Potentiation of docetaxel effect | [279] | ||||||||
MCF-7 cells, CLA-gemcitabine conjugate | Growth inhibition | [292] | MCF-7 xenografts, BALB/c mice, CLA-gemcitabine conjugate | Suppression of tumour growth | [292] | ||||
SW480 colon carcinoma, VA | Inhibition of proliferation | [275] | CT29 xenografts, BALB/c mice, dietary CLA | Metastasis inhibition | [283] | ||||
HCT-116 and HT-29 colorectal carcinoma, CLA | Isomer-dependent inhibition of proliferation, induction of apoptosis, | [282] | |||||||
1,2-dimethylhydrazine-induced colon cancer, Sprague-Dawley rats, dietary CLA | Apoptosis induction | [310] | |||||||
SW480 colon cancer cells, CLA | Isomer-dependent effect on cell invasiveness | [283] | |||||||
Azoxymethane-induced colon cancer, Sprague-Dawley rats, dietary CLA | Decrease in aberrant crypt foci formation, apoptosis induction | [311] | |||||||
Azoxymethane and dextransodium sulfate-induced colorectal cancer, 57BL/6 mice, dietary CLA | Tumour growth promotion | [312] | |||||||
Mouth/pharynx cancer risk, rTFAs | Positive association | [269] | |||||||
DU145 prostate carcinoma cells, CLA | Cell cycle inhibition | [285] | DU-145 transplants, SCID mice, dietary CLA | Inhibition of tumour growth and metastasis | [313] | ||||
R-3327-AT-1 transplants, Copenhagen rats, dietary CLA | No effect on tumour growth | [314] | |||||||
SKOV-3 and A2780 ovarian cancer cells, CLA | Isomer-dependent suppression of proliferation and migration | [284] | |||||||
RL 95-2 endometrial cancer cells, CLA | Apoptosis induction | [286] | |||||||
5-8F and CNE-2 human nasopharyngeal carcinoma | Inhibition of proliferation, induction of apoptosis | [277] | |||||||
B16-F10 melanoma, liposomes containing CLA and paclitaxel | Growth inhibition | [293] | B16-F10 melanoma transplants, C57BL6/N mice, liposomes containing CLA and paclitaxel (i.v.) | Tumour growth inhibition | [293] | Malignant melanoma risk, rTFAs intake | Negative association in women | [269] | |
Non-melanoma cancer risk, rTFAs intake | Positive association | ||||||||
Multiple myeloma risk, rTFAs intake | Negative association | [269] | |||||||
Non-Hodgkin’s lymphoma risk, rTFAs intake | Positive association |
7. Targeting Lipid Metabolism in Cancer Treatment
8. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AA | Arachidonic acid |
ALA | Alpha-linolenic acid |
AMPK | Adenosine monophosphate-activated protein kinase |
AR | Adrenergic receptor |
ATF | Activating transcription factor |
aP2 | Adipocyte fatty acid-binding protein |
CD36 | Cluster of differentiation 36 |
CDK2 | Cyclin-dependent kinase 2 |
CHOP | C/EBP homologous protein, DNA damage-inducible transcript 3 |
CI | Confidence interval |
CLA | Conjugated linoleic acid |
DHA | Docosahexaenoic acid |
DMBA | 9,10-dimethyl-1,2-benz[a]-anthracene |
EA | Elaidic acid |
EGFR | Epidermal growth factor receptor |
EMT | Epithelial-mesenchymal transition |
EPA | Eicosapentaenoic acid |
EPIC | European Prospective Investigation into Cancer and Nutrition |
ER | Endoplasmic reticulum |
ERK1/2 | Extracellular signal-regulated kinase 1/2 |
FAK | Focal adhesion kinase |
FAs | Fatty acids |
GIT | Gastrointestinal tract |
GPR | G-protein-coupled receptor |
GSK-3β | Glycogen synthase kinase-3 beta |
HDAC | Histone deacetylase |
HDACi | Histone deacetylase inhibitor |
HFD | High-fat diet |
HMGB1 | High mobility group box 1 protein |
HR | Hazard ratio |
IARC | International Agency for Research on Cancer |
IL | Interleukin |
iTFAs | Industrially produced trans fatty acids |
LaA | Lauric acid |
LA | Linoleic acid |
LPS | Lipopolysaccharides |
MA | Myristic acid |
MAPKs | Mitogen-activated protein kinases |
MCP-1 | Monocyte chemoattractant protein-1 |
MMP | Matrix metalloproteinase |
mTOR | Mammalian target of rapamycin |
MUFAs | Monounsaturated fatty acids |
NF-κB | Nuclear factor kappa B |
NMU | N-methyl-N-nitrosourea |
NOX | Nicotinamide adenine dinucleotide phosphate oxidase |
Nrf2 | Nuclear factor erythroid 2-related factor 2 |
OA | Oleic acid |
OR | Odds ratio |
p21(CIP1/WAF1) | Cyclin-dependent kinase inhibitor 1 |
p27 (KIP) | Cyclin-dependent kinase inhibitor 1B |
PA | Palmitic acid |
PCNA | Proliferating cell nuclear antigen |
PI3K | Phosphatidylinositol 3-kinase |
PPAR | Peroxisome proliferator-activated receptor |
PUFAs | Polyunsaturated fatty acids |
Q | Quintile |
RCT | Randomised controlled trial |
RNS | Reactive nitrogen species |
ROS | Reactive oxygen species |
RVLM | Rostral ventral lateral medulla |
RR | Relative risk |
rTFAs | Ruminant trans fatty acids |
SA | Stearic acid |
SREBP | Sterol regulatory element-binding protein |
SCD | Stearoyl-CoA desaturase |
SFAs | Saturated fatty acids |
STAT | Signal transducer and activator of transcription |
T | Tertile |
TFAs | Trans fatty acids |
TGF-β | Transforming growth factor beta |
TLR-4 | Toll-like receptor 4 |
TMA | Trimethylamine |
TMAO | Trimethylamine-N-oxide |
TNFα | Tumour necrosis factor alpha |
UPR | Unfolded protein response |
VA | Vaccenic acid |
XBP1 | X-box binding protein 1 |
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Bojková, B.; Winklewski, P.J.; Wszedybyl-Winklewska, M. Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence. Int. J. Mol. Sci. 2020, 21, 4114. https://doi.org/10.3390/ijms21114114
Bojková B, Winklewski PJ, Wszedybyl-Winklewska M. Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence. International Journal of Molecular Sciences. 2020; 21(11):4114. https://doi.org/10.3390/ijms21114114
Chicago/Turabian StyleBojková, Bianka, Pawel J. Winklewski, and Magdalena Wszedybyl-Winklewska. 2020. "Dietary Fat and Cancer—Which Is Good, Which Is Bad, and the Body of Evidence" International Journal of Molecular Sciences 21, no. 11: 4114. https://doi.org/10.3390/ijms21114114