Long-Chain Polyunsaturated Fatty Acids Promote Paclitaxel Cytotoxicity via Inhibition of the MDR1 Gene in the Human Colon Cancer Caco-2 Cell Line

Kuan, Cheng-Yi; Walker, Terry; Luo, Pengju G.; Chen, Chin‐Fu

doi:10.1080/07315724.2011.10719969

Cited by 55 publications

(38 citation statements)

References 54 publications

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“…A similar effect was produced by DHA and EPA in the Pgp-overexpressing Caco-2 cells treated with paclitaxel [59]. DHA and EPA fully restored both the direct cytotoxicity and the “indirect” pro-immunogenic toxicity of doxorubicin, i.e.…”

Section: Discussionmentioning

confidence: 72%

Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

et al. 2013

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BackgroundThe activity of P-glycoprotein (Pgp) and multidrug resistance related protein 1 (MRP1), two membrane transporters involved in multidrug resistance of colon cancer, is increased by high amounts of cholesterol in plasma membrane and detergent resistant membranes (DRMs). It has never been investigated whether omega 3 polyunsatured fatty acids (PUFAs), which modulate cholesterol homeostasis in dyslipidemic syndromes and have chemopreventive effects in colon cancer, may affect the response to chemotherapy in multidrug resistant (MDR) tumors.MethodsWe studied the effect of omega 3 PUFAs docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) in human chemosensitive colon cancer HT29 cells and in their MDR counterpart, HT29-dx cells.ResultsMDR cells, which overexpressed Pgp and MRP1, had a dysregulated cholesterol metabolism, due to the lower expression of ubiquitin E3 ligase Trc8: this produced lower ubiquitination rate of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCoAR), higher cholesterol synthesis, higher cholesterol content in MDR cells. We found that DHA and EPA re-activated Trc8 E3 ligase in MDR cells, restored the ubiquitination rate of HMGCoAR to levels comparable with chemosensitive cells, reduced the cholesterol synthesis and incorporation in DRMs. Omega 3 PUFAs were incorporated in whole lipids as well as in DRMs of MDR cells, and altered the lipid composition of these compartments. They reduced the amount of Pgp and MRP1 contained in DRMs, decreased the transporters activity, restored the antitumor effects of different chemotherapeutic drugs, restored a proper tumor-immune system recognition in response to chemotherapy in MDR cells.ConclusionsOur work describes a new biochemical effect of omega 3 PUFAs, which can be useful to overcome chemoresistance in MDR colon cancer cells.

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Section: Discussionmentioning

confidence: 72%

Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

et al. 2013

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“…Indeed, it has been found that ω-3 PUFAs dietary deficiency might increase vulnerability to LPS-induced spatial memory impairment (Delpech et al, 2015). Furthermore, PUFAs may affect basal and stimulated production of serotonin (Kodas et al, 2004), regulate transport of antidepressants through BBB (Kuan et al, 2011) and increase the production of BDNF (Rao et al, 2007;Vetrivel et al, 2012). In turn, the effects of PUFAs on oxidative stress remain the matter of dispute regarding safety issues since pro-oxidative effects have been also reported (Di Nunzio et al, 2016).…”

Section: Polyunsaturated Fatty Acids (Pufas)mentioning

confidence: 99%

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Misiak

Beszłej

Kotowicz

et al. 2018

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…Epidemiological studies showed that increased consumption of fish oil or LC n-3 PUFA is inversely correlated with CRC incidence [11, 12]. Studies have shown that LC n-3 PUFA have growth-inhibitory and pro-apoptotic effects on colon cancer cells such as HT-29, HCT-116, SW-480 and Caco-2 [13–15]. Animal studies showed that fish oil supplementation reduced the number and size of polyps and suppressed the growth of cancer xenografts in nude mice [16–20].…”

Section: Introductionmentioning

confidence: 99%

Krill oil extract suppresses cell growth and induces apoptosis of human colorectal cancer cells

Jayathilake

Senior

2016

BMC Complement Altern Med

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BackgroundColorectal cancer (CRC) is the third most common cancer in the world. The current available treatments for CRC include surgery, chemotherapy and radiotherapy. However, surgery is only useful when the disease is diagnosed at the earlier stage. Chemotherapy and radiotherapy are associated with numerous side effects that decrease the patients’ quality of life. Safer, effective alternatives, such as natural compounds, to chemotherapy are desirable. This study assessed the efficacy of free fatty acid (FFA) extract of krill oil on three human CRC cells lines.MethodsHCT-15, SW-480 and Caco-2 cells were treated with the FFA extracts of krill oil and fish oil for 48 h while treatments with the bioactive omega-3 polyunsaturated fatty acids (LC n-3 PUFA) of these marine oils, eicosapentaenoic acid (EPA, C20:5n-3) and docosahexaenoic acid (DHA, C22:6n-3) in comparison with a n-6 PUFA, arachnoid acid (AA, C20:4n-6) were up to 72 h at the concentrations of 50, 100, 150 and 200 μM. Effects of all the treatments on cell proliferation were assessed using a water-soluble tetrazolium-1 (WST-1) assay kit at 24, 48 and 72 h. Effects of FFA extract of krill oil and EPA on apoptosis and mitochondrial membrane potential were determined using commercial kits after 48 h of treatment.ResultsKrill oil extract inhibited cell proliferation of all three cell lines in the similar manner as fish oil extract. A significant cell apoptosis and increase in mitochondrial membrane potential were observed after the treatment with krill oil extract. EPA at the concentration of 200 μM reduced significantly the proliferation of HCT-15 and SW-480 at 24, 48 and 72 h. In addition, EPA treatment (100 and 200 μM) resulted in significant cell apoptosis in all three cell lines. No significant changes were observed after treatment with DHA and AA.ConclusionsOur results indicate that the FFA extract of krill oil maybe an effective chemotherapeutic agent to suppress proliferation and induce apoptosis in CRC cells through its bioactive constitute EPA. Although the exact mechanism of the pro-apoptotic properties of krill oil extract is unclear, mitochondrial pathway seems to be implicated.

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Long-Chain Polyunsaturated Fatty Acids Promote Paclitaxel Cytotoxicity via Inhibition of the MDR1 Gene in the Human Colon Cancer Caco-2 Cell Line

Abstract: Our results suggest that inhibition of the multidrug resistance MDR1/P-gp is one mechanism through which dietary polyunsaturated fatty acids exert a synergetic effect on the response of tumor cells to anticancer drugs.

Cited by 55 publications

References 54 publications

Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

Omega 3 fatty acids chemosensitize multidrug resistant colon cancer cells by down-regulating cholesterol synthesis and altering detergent resistant membranes composition

Cytokine alterations and cognitive impairment in major depressive disorder: From putative mechanisms to novel treatment targets

Krill oil extract suppresses cell growth and induces apoptosis of human colorectal cancer cells

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