Department of Biomedical Sciences, University of Illinois-College of Medicine, Rockford, IL, USA.
2
Department of Pathology, University of Illinois at Chicago, Chicago, IL, USA.
3
Department of Biomedical Sciences, University of Illinois-College of Medicine, Rockford, IL, USA. Electronic address: mgnanas@uic.edu.
Abstract
The aim of this study was to evaluate the therapeutic effects of vitamin K2 (VK2) on castration-resistant prostate cancer (CRPC) and its anti-cancer mechanisms in a pre-clinical study using a VCaP cell line (ATCC® CRL-2876™) which was established from a vertebral bone metastasis from a patient with hormone refractory prostate cancer. Our data showed that VK2 significantly inhibited CRPC VCaP cell proliferation in a dosedependent manner at 48 h treatment in vitro. In addition, VK2 reduced the migration potential of VCaP cells and inhibited anchorage-independent growth of these cells. Our results also showed that VK2 induces apoptosis in VCaP cells. Furthermore, VK2 enforced growth arrest in VCaP cells by activating cellular senescence. Notably, VK2 treatment elevated the levels of reactive oxygen species in VCaP cells. Western blot analysis revealed that VK2 downregulated the expression of androgen receptor, BiP, survivin, while activating caspase-3 and -7, PARP-1, p21 and DNA damage response marker, phospho-H2AX, in VCaP cells. In conclusion, our study suggests that VK2 might be a potential anti-cancer agent for CRPC by specifically targeting key anti-apoptotic, cell cycle progression and metastasis-promoting signaling molecules.
KEYWORDS:
Apoptosis; Prostate cancer; Reactive oxygen species and DNA damage; Vitamin K2
PMID: 29432837 DOI: 10.1016/j.fct.2018.02.018
Written by
pjoshea13
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One advantage of K2 for bone health is that it has a longer half-life than K1, which is quickly cleared.
Vitamin K2 is not a single menaquinone, & it is the MK-7 that is of greatest interest. Not only does some MK-7 remain in the body 24 hours later, but it is the one with anti-PCa properties.
From the EPIC study:
"During a mean follow-up time of 8.6 y, 268 incident cases of prostate cancer, including 113 advanced cases, were identified. We observed a nonsignificant inverse association between total prostate cancer and total menaquinone intake [multivariate relative risk (highest compared with lowest quartile): 0.65 ...]. The association was stronger for advanced prostate cancer (0.37 ...). Menaquinones from dairy products had a stronger inverse association with advanced prostate cancer than did menaquinones from meat. Phylloquinone intake was unrelated to prostate cancer incidence"
Note: meat provides MK-4; Phylloquinone (from greens) is K1.
Cheese is quite variable as to K2 content.
"Gouda has the highest content of vitamin K2 than any other cheese with approximately 20 mcg per ounce. Brie, Jarlsberg's and Edam are also good sources as are traditional curd cheeses. Other aged, hard cheeses have some vitamin K2 as well."
Yesterday's post about milk intake ended up saying it is pretty much ok to drink non-fat milk, and definitely stay away from regular (fatty) milk. At least that is what I remember from it.
I can understand why some might think that, but an earlier study had implicated calcium [1].
In the massive NIH-AARP study:
"Skim milk, but not other dairy foods, was associated with increased risk of advanced prostate cancer (> or = 2 vs. zero servings/day: RR = 1.23 ...)" [2]
I am grateful for all of your posts which i benefit a lot. Although because i am not native english speaker i dont understand researches you post but as far as i understand vit k is good for PCa along with vitd3.
For that reason (i think) one of the most famous Onclogist (in my country) suggests taking daily 1 glass of fresh carrotjuice and vit d3.
Is carrot juice enough for the intake of k2?
I bought a slow juicer of (omega) and give him 1 glass each day with 2-3 drops of olive oil adding in.
I am also concerned about the natural sugar carrot has but hoping he will benefit k2..
Am i doing something good?
I was thinking about carrot alot lately thank you for bringing this up and giving me chance to ask my questions.
My concern about Vitamin k1 and k2 supplements is that it can increase blood clots. That combined with lupron concerns me because I have some coronary artery disease plaque about 30% in two periphery arteries. I still do pretty good on stress test results currently.
Any thoughts on safety of the bit k1 and 2 related to coronary heart disease concerns?
There are many factors involved in coagulation. Vitamin K is essential for the production of some of these factors.
The treatment of bloodclots is a bit strange to me. Instead of dissolving the clot, the treatment involves the inhibition of a coagulation factor. This slows coagulation. The clot itself will be gradually dissolved by plasmin. The idea is to slow coagulation to the point that the clot is losing fibrin faster than it is accruing.
Warfarin blocks an enzyme (vitamin K epoxide reductase) that reactivates vitamin K1. Restricted vitamin K means less factors II, VII, IX, and X.
Warfarin therapy is somewhat like ADT in the sense that testosterone does not cause PCa, but castration is a convenient treatment. As with ADT there are big downsides to Warfarin. Calcium transport to bone is inhibited, resulting in osteopenia or osteoporosis. Calcification of the arteries increases & there is greater chance of a cardiovascular event. The risk of bleedout following an accident is increased. It is one of the leading med-related causes of ER visits.
The aim of Warfarin treatment is to increase clotting time, as measured by the INR (therapeutic range is 2-3). Normally, the INR is ~1.0 (0.8-1.2), and this is so even with a DVT (as I once discovered.) You can eat a plate of greens at every meal & you will not reduce clotting time unless on Warfarin. The only reason to avoid vitamin K is when it is the target of anticoagulation meds.
It should be noted that drugs that target other coagulation factors without inhibiting vitamin K, do not come with warnings to restrict K intake.
As for plaque, if this involves calcium, vitamin K can actually remove it from arterial walls.
When she was 65, my wife had a calcium scan. Not covered by insurance, but it is dirt cheap. It measures calcium buildup in the arteries that enter/exit the heart. She had zero calcium in all four of her results. Her doctor told her that it was unheard of in a woman of her age. She had been on K2 for maybe 4 years.
Dr. Warburg identified K2 as as seriously beneficial in part because he confirmed that cancer cells get energy from anaerobic yeast fermentation rather than aerobic processes in normal cells.
This could provide some insight why cancer need fat to thrive and the basis of the benefits of meformin/statins to deprive cancer cells of that energy source. It may also provide an insight on why cancer cells appear to die in cryogenic and high oxygen therpies
I would be on K2 however I am currently using estrogen/Estradiol to successfully deprive the cancer of testosterone. K2 degrades estrogen so is counterproductive for me.
However I have read multiple sources suggesting that K2 works in synergy with coQ10 or in its best form is called Ubiquinol.
darn, I just typed a long reply and then my comp locked up and lost it.
Thanks for the info pjoshea. Pertercraig, is estrogen/Estradiol the same as Lupron? I take Lupron for prostate cancer. I don't want to interfere with my cancer treatment. Was also going to add zytiga/prednisone soon possibly.
I saw you take metformin. What do you take that for? I thought berberine might be good for me but I decided its blood thinning effect might be took much since I'm on aspirin and coffee daily. I did add pomegranate extract, L-prolyne, L-Lysine and L-argenine to my supplements for artery health and I try to eat garlic.
Do you think adding K2 to my calcium/vit D3, ubiqinuol, magnesium every evening is a good idea?
To answer for Peter: high-dose estradiol [E2] is as good as Lupron for curtailing gonadal T production.
Berberine can be used in place of Metformin. Rich has asked for a review of Berberine, which I will do. But Metformin now has many PCa papers, whereas no-one is going to do a berberine PCa clinical trial IMO.
Aspirin doesn't thin blood - it inhibits platelet aggregation, which is the first step of clotting at a wound site. PCa disrupts coagulation so much, that I would not trust aspirin for protection. D-dimer of zero means no clots. The best way of making sure that there isn't an ER visit in your future because of a DVT.
K2 is always a good idea. The MK-7 protects against PCa, & K2 is needed for calcium transport to bone (& away from arterial walls.) Excess calcium in circulation will inhibit hormonal vitamin D creation.
I use nattokinase to dissolve fibrin. The body does this nore slowly with plasmin. When the fibrin in a clot is being dissolved, there are breakdown products. This is what D-dimer measures.
So the D-dimer test is a verification that there is no clot. Or a warning that there is coagulation activity.
But having had a DVT, I take nattokinase every day, to stay ahead of any activity. I don't think I would trust aspirin to protect me.
I admire your courage in using natto itself. We must have a dozen restaurants that serve Japanese food, but only one that offers natto. I haven't tried it.
The stuff may well last for ever, but how would one tell that it has gone bad? LOL.
I never thought of the nattokinase supplement caps. I suppose they have the same effect as the natural form. I just figure that since my healthy smoothies already taste awful, that a little natto in there couldn't make it much worse. It's like going from a 3/10 to a 2/10 in taste. I'll let you know how it turn out after I but some fresh natto from the marker.
I'm taking K2, magnesium, calcium and D3. nattokinase shouldn't interfere with those if I only take 100mg of nattokinase per day, right? I'm not on any other blood thinners and I keep the K2 to RDA amounts 45mcg 1ea morning and night.
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