Docosahexaenoic Acid Induces Apoptosis in MCF-7 Cells In Vitro and In Vivo via Reactive Oxygen Species Formation and Caspase 8 Activation

Kang, Ki Sung; Wang, Pan; Yamabe, Noriko; Fukui, Masayuki; Jay, Taylor R.; Zhu, Bao Ting

doi:10.1371/journal.pone.0010296

Cited by 185 publications

(159 citation statements)

References 39 publications

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“…A previous study in Japan documented that the mean concentration of serum DHA in healthy controls was 18.52 mg/dl (563.0 µM) (17) and previous studies investigating the anti-tumor effects of DHA on colon (18), breast (19) and prostate cancer cells in vivo (20) have used DHA concentrations between 10 and 200 µM. Therefore, the present study used DHA concentrations ≤100 µM to obtain clinically relevant results.…”

Section: Discussionmentioning

confidence: 96%

“…Therefore, studies aiming to identify a novel therapeutic agent to treat patients with metastatic RCC are required. The present study used in vitro techniques including MTS and proliferation assays and flow cytometry analysis to investigate the anti-tumor activities of DHA on the proliferative and invasive capacities of RCC cells at clinically relevant concentrations of 10-200 µM, as previously determined (17)(18)(19)(20) Cell proliferation was assessed by counting cell numbers after cells seeded into 6-well plates (1x10 4 cells/well) had been incubated at 37˚C with DHA (0, 50, 100 µM) for 0, 24, 48 and 72 h. The medium used for Caki-1 cells was 1X MEM with 10% FBS and the medium for 786-O cells was RPMI medium 1640 with 10% FBS, as previously stated. Total cell numbers were then counted in four fields using a hemocytometer and mean values were calculated from three replicates.…”

Section: Introductionmentioning

confidence: 99%

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Docosahexaenoic acid inhibits the phosphorylation of STAT3 and the growth and invasion of renal cancer cells

Tasaki

Horiguchi

Ito

et al. 2017

Experimental and Therapeutic Medicine

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Abstract. Docosahexaenoic acid (DHA) has a variety of anti-tumor activities. The present study examined the anti-tumor activity of DHA in renal cancer cells and its underlying mechanisms of action. The effects of DHA on the viability and proliferation of the human renal cancer cell lines Caki-1 and 786-O were examined by an MTS assay and cell counting. In addition, cell cycle distribution and cell apoptosis were analyzed by flow cytometry and Annexin V staining, and modulation of cell mobility and invasiveness was assessed by wound healing and Matrigel invasion assays. Effects of DHA on intracellular signaling pathways were also analyzed by western blotting. It was observed that DHA significantly reduced the viability and proliferation of Caki-1 and 786-O cells (P<0.01). Specifically, there were increases in the sub-G1 and G2/M cell populations, as well as the percentages of cells exhibiting Annexin-positive and propidium-iodide-negative staining. In addition, the covered area in a wound and the number of cells invading through a Matrigel chamber decreased when Caki-1 or 786-O cells were treated with DHA. Phosphorylation of epidermal growth factor receptor was also upregulated following DHA treatment, while phosphorylation of signal transducer and activator of transcription 3 and Akt was downregulated. Collectively, these data suggest that DHA may be useful in the treatment of renal cell carcinoma.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Docosahexaenoic acid inhibits the phosphorylation of STAT3 and the growth and invasion of renal cancer cells

Tasaki

Horiguchi

Ito

et al. 2017

Experimental and Therapeutic Medicine

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“…The mixture was incubated for 1 h, following which the liquid in the wells was removed. Subsequently, 50 µl dimethyl sulfoxide was added to each well and incubated for 10 min, and the absorbance was recorded using a UV Max microplate reader (Molecular Devices, Palo Alto, CA, USA) at 595 nm (19).…”

Section: Methodsmentioning

confidence: 99%

Induction of apoptosis in MCF-7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium)

Kim

et al. 2015

Molecular Medicine Reports

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Abstract. Khz (fusion of Ganoderma lucidum and Polyporus umbellatus), isolated from the mycelia of G. lucidum and P. umbellatus, exerts anti-proliferative effects against malignant cells; however, its activity against human breast cancer cells remains to be elucidated. In the present study, cell proliferation was assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and poptosis was examined using annexin V-propidium iodide staining and flow cytometry. The activation of caspases 7, 8 and 9 were detected in the Khz-treated cells using western blotting. The results demonstrated that Khz increased the intracellular calcium concentration and induced the production of reactive oxygen species in MCF-7 breast cancer cells, as determined using flow cytometry. The results also demonstrated that Khz inhibited cell proliferation and induced apoptosis in the MCF-7 cells. In addition, the mechanism by which Khz induces apoptosis in cancer cells was investigated. Khz induced apoptosis preferentially in transformed cells, with a minimal effect on non-transformed cells, suggesting its potential as an anticancer therapeutic agent. Oxidative stress is associated with apoptotic and non-apoptotic cell death, although pro-oxidative conditions are not a pre-requisite for apoptosis. Assessment of the activation status of caspases 7, 8 and 9 revealed that the levels of cleaved caspases were significantly increased in the cells treated with Khz. It is widely accepted that calcium signaling is important in apoptosis, and the present study observed an increase in [Ca 2+ ] i in response to Khz treatment. The anti-proliferative and pro-apoptotic effects of Khz suggest that this extract may be developed as a potential anticancer agent.

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“…44 For breast cancer cells MCF-7, MDA-MB-231, and MDA-MB-435, the IC 50 were 20.2, 57.4, and 70 µM, respectively, when treated with DHA. 45 However, a smaller IC 50 was shown for ovarian cancer cell PA-1, lung cancer cell H1299, glial tumor cell D54MG, and cervical cancer cell …”

Section: Cell Viability Of B16-f10 and Ccd986sk Cellsmentioning

confidence: 99%

Preparation of coffee oil-algae oil-based nanoemulsions and the study of their inhibition effect on UVA-induced skin damage in mice and melanoma cell growth

Yang¹,

Hung²,

Chen³

2017

IJN

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Coffee grounds, a waste by-product generated after making coffee, contains approximately 15% coffee oil which can be used as a raw material in cosmetics. Algae oil rich in docosahexaenoic acid (DHA) has been demonstrated to possess anticancer and anti-inflammation functions. The objectives of this study were to develop a gas chromatography-mass spectrometry (GC-MS) method for the determination of fatty acids in coffee oil and algae oil and prepare a nanoemulsion for studying its inhibition effect on ultraviolet A-induced skin damage in mice and growth of melanoma cells B16-F10. A total of 8 and 5 fatty acids were separated and quantified in coffee oil and algae oil by GC-MS, respectively, with linoleic acid (39.8%) dominating in the former and DHA (33.9%) in the latter. A nanoemulsion with a particle size of 30 nm, zeta potential −72.72 mV, and DHA encapsulation efficiency 100% was prepared by using coffee oil, algae oil, surfactant (20% Span 80 and 80% Tween 80), and deionized water. Differential scanning calorimetry (DSC) analysis revealed a high stability of nanoemulsion when heated up to 110°C at a pH 6, whereas no significant changes in particle size distribution and pH occurred over a 90-day storage period at 4°C. Animal experiments showed that a dose of 0.1% coffee oil-algae oil nanoemulsion was effective in mitigating trans-epidermal water loss, skin erythema, melanin formation, and subcutaneous blood flow. Cytotoxicity test implied effective inhibition of melanoma cell growth by nanoemulsion with an IC 50 value of 26.5 µg/mL and the cell cycle arrested at G2/M phase. A dose-dependent upregulation of p53, p21, cyclin B, and cyclin A expressions and downregulation of CDK1 and CDK2 occurred. Also, both Bax and cytochrome c expressions were upregulated and bcl-2 expression downregulated, accompanied by a rise in caspase-3, caspase-8, and caspase-9 activities for apoptosis execution. Collectively, the apoptosis pathway of melanoma cells B16-F10 may involve both mitochondria and death receptor.

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Docosahexaenoic Acid Induces Apoptosis in MCF-7 Cells In Vitro and In Vivo via Reactive Oxygen Species Formation and Caspase 8 Activation

Cited by 185 publications

References 39 publications

Docosahexaenoic acid inhibits the phosphorylation of STAT3 and the growth and invasion of renal cancer cells

Docosahexaenoic acid inhibits the phosphorylation of STAT3 and the growth and invasion of renal cancer cells

Induction of apoptosis in MCF-7 human breast cancer cells by Khz (fusion of Ganoderma lucidum and Polyporus umbellatus mycelium)

Preparation of coffee oil-algae oil-based nanoemulsions and the study of their inhibition effect on UVA-induced skin damage in mice and melanoma cell growth

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