La Vitamina k2 uccide le cellule tumorali del cancro al seno

Questa è veramente la vitamina, anzi la sostanza, del decennio.

​Infatti, dopo aver dimostrato di agire sulla prevenzione delle malattie cardio-vascolari, le calcificazioni in genere e nella malattie autoimmuni, sempre più ricerche pongono la Vitamina K2 in prima linea anche contro il cancro.

In questo caso parliamo del tumore più diffuso nelle donne al mondo. 

In Italia vivono più di 37.000 donne con diagnosi di tumore della mammella metastatico e ci sono  10mila nuove pazienti italiane che ogni anno lottano contro un carcinoma mammario avanzato.

E' il tumore più frequente tra quelli che colpiscono il sesso femminile e rappresenta il 29% delle diagnosi oncologiche totali.

E' vero che grazie alla ricerca, fino all’88% delle pazienti colpite è ancora in vita dopo 5 anni dalla diagnosi.

Il doppio rispetto a solo venti anni fa.

Ma solo il 16% delle donne guarisce completamente, cioè gode di un rischio di mortalità analogo a quello delle coetanee mai colpite da tumore.

Quest’ultimo dato è certamente meno diffuso: si parla spesso dei risultati ottenuti nella diagnosi precoce e nella cura in fase iniziale, ma non delle migliaia di donne che convivono con la malattia metastatica, ovvero diffusasi in organi diversi da quello da cui ha avuto origine, in particolare ossa, cervello, fegato e polmoni.

Se una donna viene colpita dal cancro al seno non si controlla quasi mai il livello di vitamina D e, tantomeno, l' apporto di Vitamina K2. 

Eppure un altro studio (*) ha  portato riportato dei dati veramente interessanti proprio riguardo il cancro al seno. 

Per esempio, ci sono state diverse segnalazioni che la vitamina K 2 (VK2) induce l'apoptosi in molti tipi di cellule tumorali, compresa la leucemia (1-56).

L' apoptosi è un processo di morte cellulare controllato geneticamente. 

Tuttavia, non ci sono rapporti precisi riguardanti le cellule tumorali al seno.

Dal punto di vista delle implicazioni cliniche della VK2, inclusa la chemioprevenzione, in questa ricerca sono stati studiati gli effetti della VK2 sulle linee cellulari di carcinoma mammario.

Le linee cellulari di cancro al seno sono state coltivate con VK2 e sono stati esaminati la citotossicità e il fenotipo di morte cellulare (accumulo di mutazioni maligne).

La citotossicità è l' insieme di attività biologiche di cellule del sistema immunitario che porta alla morte per apoptosi di cellule infettate da virus o di batteri intracellulari o non appartenenti all’ospite.

Le cellule della leucemia HL-60 sono state usate come controllo per l'apoptosi indotta da VK2.

RISULTATI:

La Vitamina K2 ha mostrato l'effetto citotossico, in particolare nelle linee cellulari triplo negative di carcinoma mammario.

Il Vitamina K2 ha indotto la morte cellulare (insieme all'autofagia), in linee cellulari di cancro al seno.

L’autofagia è un processo che la cellula mette in pratica, in genere, in caso di carenza di nutrienti; prevede la fagocitosi dei suoi stessi organelli.

Il fenotipo di morte cellulare indotto da Vitamina K2 sembra differire tra i tipi di tumori.

Ciò suggerisce la possibilità di utilizzare Vitamina K2 per la terapia del cancro al seno.

Sia per la prevenzione e per il trattamento di questo grave tipo di cancro bisogna consumare cibi ricchi di Vitamina K2 come verdure, carne grass fed (cioè allevate ad erba) e burro ghee grass fed come Brado. 

A questo sarebbe ottimo affiancare un integratore specifico di Vitamina K2 (specialmente se il tumore è già in atto) come "Primal K2 1000" QUI


​
Fonte: *Breast Cancer. 2019 Oct 17. doi: 10.1007/s12282-019-01012-y. Vitamin K2 induces non-apoptotic cell death along with autophagosome formation in breast cancer cell lines. Miyazawa S1, Moriya S2, Kokuba H3, Hino H2, Takano N2, Miyazawa K4.


1. Ogawa M, Nakai S, Deguchi A, Nonomura T, Masaki T, Uchida N, Yoshiji H,
Kuriyama S.   K2, K3 and K5 exert antitumor effects on established
colorectal cancer in mice by inducing apoptotic death of tumor cells. Int J Oncol.
2007;31:323–331. [PubMed]
2. Yoshida H, Shiratori Y, Kudo M, Shiina S, Mizuta T, Kojiro M, Yamamoto K, Koike Y,
Saito K, Koyanagi N, et al. Effect of vitamin K2 on the recurrence of hepatocellular
carcinoma. Hepatology. 2011;54:532–540. doi: 10.1002/hep.24430. [PubMed] [Cross Ref]
3. Li ZQ, He FY, Stehle CJ, Wang Z, Kar S, Finn FM, Carr BI. Vitamin K uptake in
hepatocytes and hepatoma cells. Life Sci. 2002;70:2085–2100. doi: 10.1016/S0024-
3205(01)01525-9. [PubMed] [Cross Ref]
4. Iwamoto J, Takeda T, Sato Y. Effects of vitamin K2 on osteoporosis. Curr Pharm
Des. 2004;10:2557–2576. doi: 10.2174/1381612043383782. [PubMed] [Cross Ref]
5. Ushiroyama T, Ikeda A, Ueki M. Effect of continuous combined therapy with
vitamin K(2) and vitamin D(3) on bone mineral density and coagulofibrinolysis
function in postmenopausal women. Maturitas. 2002;41:211–221. doi: 10.1016/S0378-
5122(01)00275-4. [PubMed] [Cross Ref]
6. Bouzahzah B, Nishikawa Y, Simon D, Carr BI. Growth control and gene expression
in a new hepatocellular carcinoma cell line, Hep40: Inhibitory actions of vitamin K.
J Cell Physiol. 1995;165:459–467. doi: 10.1002/jcp.1041650303. [PubMed] [Cross Ref]
7. Hitomi M, Yokoyama F, Kita Y, Nonomura T, Masaki T, Yoshiji H, Inoue H, Kinekawa
F, Kurokohchi K, Uchida N, et al. Antitumor effects of vitamins K1, K2 and K3 on
hepatocellular carcinoma in vitro and in vivo. Int J Oncol. 2005;26:713–720. [PubMed]
8. Takami A, Nakao S, Ontachi Y, Yamauchi H, Matsuda T. Successful therapy of
myelodysplastic syndrome with menatetrenone, a vitamin K2 analog. Int J Hematol.
1999;69:24–26. [PubMed]
9. Fujita H, Tomiyama J, Tanaka T. Vitamin K2 combined with all-trans retinoic acid
induced complete remission of relapsing acute promyelocytic leukaemia. Br J
Haematol. 1998;103:584–585. doi: 10.1046/j.1365-2141.1998.01088.x. [PubMed] [Cross Ref]
10. Yoshiji H, Noguchi R, Yamazaki M, Ikenaka Y, Sawai M, Ishikawa M, Kawaratani
H, Mashitani T, Kitade M, Kaji K, et al. Combined treatment of vitamin K2 and
angiotensin-converting enzyme inhibitor ameliorates hepatic dysplastic nodule in a
patient with liver cirrhosis. World J Gastroenterol. 2007;13:3259–3261. doi: 10.3748/
wjg.v13.i23.3259. [PMC free article] [PubMed] [Cross Ref]
11. Otsuka T, Hagiwara S, Tojima H, Yoshida H, Takahashi T, Nagasaka K, Tomioka
S, Ando T, Takeuchi K, Kori T, et al. Hepatocellular carcinoma with peritoneal
dissemination which was regressed during vitamin K2 and vitamin E administration.
Intern Med. 2007;46:711–715. doi: 10.2169/internalmedicine.46.6131. [PubMed]
[Cross Ref]
12. Miyazawa K, Nishimaki J, Ohyashiki K, Enomoto S, Kuriya S, Fukuda R,
Hotta T, Teramura M, Mizoguchi H, Uchiyama T, Omine M. Vitamin K2 therapy
for myelodysplastic syndromes (MDS) and post-MDS acute myeloid leukemia:
Information through a questionnaire survey of multi-center pilot studies in Japan.
Leukemia. 2000;14:1156–1157. doi: 10.1038/sj.leu.2401790. [PubMed] [Cross Ref]
13. Sada E, Abe Y, Ohba R, Tachikawa Y, Nagasawa E, Shiratsuchi M, Takayanagi R. Vitamin K2 modulates differentiation and apoptosis of both myeloid and erythroid lineages. Eur J Haematol. 2010;85:538–548. doi: 10.1111/j.1600-0609.2010.01530.x. [PubMed] [Cross Ref]
14. Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, Nishiguchi S. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004;292:358–361. doi: 10.1001/jama.292.3.358. [PubMed] [Cross Ref]
15. Kojima K, Tamano M, Akima T, Hashimoto T, Kuniyoshi T, Maeda C, Majima Y, Kusano K, Murohisa T, Iijima M, Hiraishi H. Effect of vitamin K2 on the development of hepatocellular carcinoma in type C cirrhosis. Hepatogastroenterology. 2010;57:1264–1267. [PubMed]
16. Mizuta T, Ozaki I, Eguchi Y, Yasutake T, Kawazoe S, Fujimoto K, Yamamoto K. The effect of menatetrenone, a vitamin K2 analog, on disease recurrence and survival in patients with hepatocellular carcinoma after curative treatment: A pilot study. Cancer. 2006;106:867–872. doi: 10.1002/cncr.21667. [PubMed] [Cross Ref]
17. Kakizaki S, Sohara N, Sato K, Suzuki H, Yanagisawa M, Nakajima H, Takagi H, Naganuma A, Otsuka T, Takahashi H, et al. Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection. J Gastroenterol Hepatol. 2007;22:518–522. doi: 10.1111/j.1440-1746.2007.04844.x. [PubMed] [Cross Ref]
18. Ishizuka M, Kubota K, Shimoda M, Kita J, Kato M, Park KH, Shiraki T. Effect of menatetrenone, a vitamin k2 analog, on recurrence of hepatocellular carcinoma after surgical resection: A prospective randomized controlled trial. Anticancer Res. 2012;32:5415–5420. [PubMed]
19. Zhong JH, Mo XS, Xiang BD, Yuan WP, Jiang JF, Xie GS, Li LQ. Postoperative use of the chemopreventive vitamin K2 analog in patients with hepatocellular carcinoma. PLoS One. 2013;8:58082. doi: 10.1371/journal.pone.0058082. [PMC free article] [PubMed] [Cross Ref]
20. Yoshiji H, Kuriyama S, Noguchi R, Yoshii J, Ikenaka Y, Yanase K, Namisaki T, Kitade M, Yamazaki M, Masaki T, Fukui H. Combination of vitamin K2 and the angiotensin-converting enzyme inhibitor, perindopril, attenuates the liver enzyme-altered preneoplastic lesions in rats via angiogenesis suppression. J Hepatol. 2005;42:687–693. doi: 10.1016/j.jhep.2004.12.025. [PubMed] [Cross Ref]
21. Zhang Y, Zhang B, Zhang A, Zhao Y, Zhao J, Liu J, Gao J, Fang D, Rao Z. Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells. Clinics. 2012;67:1093–1099. doi: 10.6061/clinics/2012(09)18. [PMC free article] [PubMed] [Cross Ref]
22. Sakakima Y, Hayakawa A, Nagasaka T, Nakao A. Prevention of hepatocarcinogenesis with phosphatidylcholine and menaquinone-4: In vitro and in vivo experiments. J Hepatol. 2007;47:83–92. doi: 10.1016/j.jhep.2007.01.030. [PubMed] [Cross Ref]
23. Ozaki I, Zhang H, Mizuta T, Ide Y, Eguchi Y, Yasutake T, Sakamaki T, Pestell RG, Yamamoto K. Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor kappaB activation. Clin Cancer Res. 2007;13:2236–2245. doi: 10.1158/1078-0432.CCR-06-2308. [PubMed] [Cross Ref]
24. Xia J, Matsuhashi S, Hamajima H, Iwane S, Takahashi H, Eguchi Y, Mizuta T, Fujimoto K, Kuroda S, Ozaki I. The role of PKC isoforms in the inhibition of NF-kappaB activation by vitamin K2 in human hepatocellular carcinoma cells. J Nutr Biochem. 2012;23:1668–1675. doi: 10.1016/j.jnutbio.2011.11.010. [PubMed] [Cross Ref]
25. Sibayama-Imazu T, Fujisawa Y, Masuda Y, Aiuchi T, Nakajo S, Itabe H, Nakaya K. Induction of apoptosis in PA-1 ovarian cancer cells by vitamin K2 is associated with an increase in the level of TR3/Nur77 and its accumulation in mitochondria and nuclei. J Cancer Res Clin Oncol. 2008;134:803–812. doi: 10.1007/s00432-007-0349-z. [PubMed] [Cross Ref]
26. Showalter SL, Wang Z, Costantino CL, Witkiewicz AK, Yeo CJ, Brody JR, Carr BI. Naturally occurring K vitamins inhibit pancreatic cancer cell survival through a caspase-dependent pathway. J Gastroenterol Hepatol. 2010;25:738–744. doi: 10.1111/j.1440-1746.2009.06085.x. [PubMed] [Cross Ref]
27. Enomoto M, Tsuchida A, Miyazawa K, Yokoyama T, Kawakita H, Tokita H, Naito M, Itoh M, Ohyashiki K, Aoki T. Vitamin K2-induced cell growth inhibition via autophagy formation in cholangiocellular carcinoma cell lines. Int J Mol Med. 2007;20:801–808. [PubMed]
28. Miyazawa K, Yaguchi M, Funato K, Gotoh A, Kawanishi Y, Nishizawa Y, You A, Ohyashiki K. Apoptosis/differentiation-inducing effects of vitamin K2 on HL-60 cells: Dichotomous nature of vitamin K2 in leukemia cells. Leukemia. 2001;15:1111–1117. doi: 10.1038/sj.leu.2402155. [PubMed] [Cross Ref]
29. Karin M, Ben-Neriah Y. Phosphorylation meets ubiquitination: The control of NF-[kappa]B activity. Annu Rev Immunol. 2000;18:621–663. doi: 10.1146/annurev.immunol.18.1.621. [PubMed] [Cross Ref]
30. Masaki T, Shiratori Y, Rengifo W, Igarashi K, Yamagata M, Kurokohchi K, Uchida N, Miyauchi Y, Yoshiji H, Watanabe S, et al. Cyclins and cyclin-dependent kinases: Comparative study of hepatocellular carcinoma versus cirrhosis. Hepatology. 2003;37:534–543. doi: 10.1053/jhep.2003.50112. [PubMed] [Cross Ref]
31. Karin M, Delhase M. The I kappa B kinase (IKK) and NF-kappa B: Key elements of proinflammatory signalling. Semin Immunol. 2000;12:85–98. doi: 10.1006/smim.2000.0210. [PubMed] [Cross Ref]
32. Holden NS, Squires PE, Kaur M, Bland R, Jones CE, Newton R. Phorbol ester-stimulated NF-kappaB-dependent transcription: Roles for isoforms of novel protein kinase C. Cell Signal. 2008;20:1338–1348. doi: 10.1016/j.cellsig.2008.03.001. [PubMed] [Cross Ref]
33. Otsuka M, Kato N, Shao RX, Hoshida Y, Ijichi H, Koike Y, Taniguchi H, Moriyama M, Shiratori Y, Kawabe T, Omata M. Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation. Hepatology. 2004;40:243–251. doi: 10.1002/hep.20260. [PubMed] [Cross Ref]
34. Liu W, Nakamura H, Yamamoto T, Ikeda N, Saito M, Ohno M, Hara N, Imanishi H,
Shimomura S, Yamamoto T, et al. Vitamin K2 inhibits the proliferation of HepG2 cells by up-regulating the transcription of p21 gene. Hepatol Res. 2007;37:360–365. doi: 10.1111/j.1872-034X.2007.00058.x. [PubMed] [Cross Ref]
35. Maniwa Y, Kasukabe T, Kumakura S. Vitamin K2 and cotylenin A synergistically induce monocytic differentiation and growth arrest along with the suppression of c-MYC expression and induction of cyclin G2 expression in human leukemia HL-60 cells. Int J Oncol. 2015;47:473–480. doi: 10.3892/ijo.2015.3028. [PMC free article] [PubMed] [Cross Ref]
36. Yamamoto T, Nakamura H, Liu W, Cao K, Yoshikawa S, Enomoto H, Iwata Y, Koh N, Saito M, Imanishi H, et al. Involvement of hepatoma-derived growth factor in the growth inhibition of hepatocellular carcinoma cells by vitamin K(2) J Gastroenterol. 2009;44:228–235. doi: 10.1007/s00535-008-2304-4. [PubMed] [Cross Ref]
37. Kaneda M, Zhang D, Bhattacharjee R, Nakahama K, Arii S, Morita I. Vitamin K2 suppresses malignancy of HuH7 hepatoma cells via inhibition of connexin 43. Cancer Lett. 2008;263:53–60. doi: 10.1016/j.canlet.2007.12.019. [PubMed] [Cross Ref]
38. Trosko JE. The role of stem cells and gap junctions as targets for cancer chemoprevention and chemotherapy. Biomed Pharmacother. 2005;59(Suppl 2):S326–S331. doi: 10.1016/S0753-3322(05)80065-4. [PubMed] [Cross Ref]
39. Karasawa S, Azuma M, Kasama T, Sakamoto S, Kabe Y, Imai T, Yamaguchi Y, Miyazawa K, Handa H. Vitamin K2 covalently binds to Bak and induces Bak-mediated apoptosis. Mol Pharmacol. 2013;83:613–620. doi: 10.1124/mol.112.082602. [PubMed] [Cross Ref]
40. Shibayama-Imazu T, Sonoda I, Sakairi S, Aiuchi T, Ann WW, Nakajo S, Itabe H, Nakaya K. Production of superoxide and dissipation of mitochondrial transmembrane potential by vitamin K2 trigger apoptosis in human ovarian cancer TYK-nu cells. Apoptosis. 2006;11:1535–1543. doi: 10.1007/s10495-006-7979-5. [PubMed] [Cross Ref]
41. Tsujioka T, Miura Y, Otsuki T, Nishimura Y, Hyodoh F, Wada H, Sugihara T. The mechanisms of vitamin K2-induced apoptosis of myeloma cells. Haematologica. 2006;91:613–619. [PubMed]
42. Nishimaki J, Miyazawa K, Yaguchi M, Katagiri T, Kawanishi Y, Toyama K, Ohyashiki K, Hashimoto S, Nakaya K, Takiguchi T. Vitamin K2 induces apoptosis of a novel cell line established from a patient with myelodysplastic syndrome in blastic transformation. Leukemia. 1999;13:1399–1405. doi: 10.1038/sj.leu.2401491. [PubMed] [Cross Ref]
43. Kanamori T, Shimizu M, Okuno M, Matsushima-Nishiwaki R, Tsurumi H, Kojima S, Moriwaki H. Synergistic growth inhibition by acyclic retinoid and vitamin K2 in human hepatocellular carcinoma cells. Cancer Sci. 2007;98:431–437. doi: 10.1111/j.1349-7006.2006.00384.x. [PubMed] [Cross Ref]
44. Olson JM, Hallahan AR. p38 MAP kinase: A convergence point in cancer therapy. Trends Mol Med. 2004;10:125–129. doi: 10.1016/j.molmed.2004.01.007. [PubMed] [Cross Ref]
45. Li L, Qi Z, Qian J, Bi F, Lv J, Xu L, Zhang L, Chen H, Jia R. Induction of apoptosis in hepatocellular carcinoma Smmc-7721 cells by vitamin K(2) is associated with p53 and independent of the intrinsic apoptotic pathway. Mol Cell Biochem. 2010;342:125–131. doi: 10.1007/s11010-010-0476-8. [PubMed] [Cross Ref]
46. Meek DW. Tumour suppression by p53: A role for the DNA damage response? Nat Rev Cancer. 2009;9:714–723. doi: 10.1038/nrc2716. [PubMed] [Cross Ref]
47. Muzio M, Stockwell BR, Stennicke HR, Salvesen GS, Dixit VM. An induced proximity model for caspase-8 activation. J Biol Chem. 1998;273:2926–2930. doi: 10.1074/jbc.273.5.2926. [PubMed] [Cross Ref]
48. Yokoyama T, Miyazawa K, Naito M, Toyotake J, Tauchi T, Itoh M, You A, Hayashi Y, Georgescu MM, Kondo Y, et al. Vitamin K2 induces autophagy and apoptosis simultaneously in leukemia cells. Autophagy. 2008;4:629–640. doi: 10.4161/auto.5941. [PubMed] [Cross Ref]
49. Ide Y, Zhang H, Hamajima H, Kawaguchi Y, Eguchi Y, Mizuta T, Yamamoto K, Fujimoto K, Ozaki I. Inhibition of matrix metalloproteinase expression by menatetrenone, a vitamin K2 analogue. Oncol Rep. 2009;22:599–604. [PubMed]
50. Karin M. The regulation of AP-1 activity by mitogen-activated protein kinases. Philos Trans R Soc Lond B Biol Sci. 1996;351:127–134. doi: 10.1098/rstb.1996.0008. [PubMed] [Cross Ref]
51. Zhang H, Ozaki I, Hamajima H, Iwane S, Takahashi H, Kawaguchi Y, Eguchi Y, Yamamoto K, Mizuta T. Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-κB activation. Oncol Rep. 2011;25:159–166. [PubMed]
52. Funato K, Miyazawa K, Yaguchi M, Gotoh A, Ohyashiki K. Combination of 22-oxa-1,25-dihydroxyvitamin D(3), a vitamin D(3) derivative, with vitamin K(2) (VK2) synergistically enhances cell differentiation but suppresses VK2-inducing apoptosis in HL-60 cells. Leukemia. 2002;16:1519–1527. doi: 10.1038/sj.leu.2402614. [PubMed] [Cross Ref]
53. Iguchi T, Miyazawa K, Asada M, Gotoh A, Mizutani S, Ohyashiki K. Combined treatment of leukemia cells with vitamin K2 and 1alpha,25-dihydroxy vitamin D3 enhances monocytic differentiation along with becoming resistant to apoptosis by induction of cytoplasmic p21CIP1. Int J Oncol. 2005;27:893–900. [PubMed]
54. Nimptsch K, Rohrmann S, Kaaks R, Linseisen J. Dietary vitamin K intake in relation to cancer incidence and mortality: Results from the Heidelberg cohort of the European Prospective Investigation into cancer and nutrition (EPIC-Heidelberg) Am J Clin Nutr. 2010;91:1348–1358. doi: 10.3945/ajcn.2009.28691. [PubMed] [Cross Ref]
55. Yoshiji H, Kuriyama S, Noguchi R, Yoshii J, Ikenaka Y, Yanase K, Namisaki T, Kitade M, Yamazaki M, Akahane T, et al. Miglioramento della carcinogenesi e della crescita del tumore nel fegato del ratto mediante combinazione di vitamina K2 e inibitore dell’enzima di conversione dell’angiotensina tramite attività anti-angiogeniche. Oncol Rep. 2006; 15 : 155-159. [ PubMed ]
56. Oncol Lett. 2018 Jun;15(6):8926-8934. doi: 10.3892/ol.2018.8502. Epub 2018 Apr 16.
Research progress on the anticancer effects of vitamin K2. Xv F1, Chen J2, Duan
L2, Li S1.




PAROLE CHIAVE:
L'apoptosi; L'autofagia; Cancro al seno; Specie reattive dell'ossigeno; Vitamina K2