Vitamin K2, a Menaquinone Present in Dairy Products Targets Castration-resistant Prostate Cancer Cell-line by Activating Apoptosis Signaling

Overview

Journal Food Chem Toxicol

Specialties Nutritional Sciences
Toxicology

Date 2018 Feb 13

PMID 29432837

Citations 21

Authors

Subramanyam Dasari

Angela Lincy Prem Antony Samy

Andre Kajdacsy-Balla

Maarten C Bosland

Gnanasekar Munirathinam

Affiliations

Soon will be listed here.

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 dose-dependent 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 cleavage, 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.

Citing Articles

Metal-Phenolic Networks: A Promising Frontier in Cancer Theranostics.

Li L, Pan J, Huang M, Sun J, Wang C, Xu H Int J Nanomedicine. 2024; 19:11379-11395.

PMID: 39524920 PMC: 11550784. DOI: 10.2147/IJN.S491421.

Role of Vitamins in Therapeutic and Targeting Approaches for Prostate Cancer: An Overview.

Panda P, Saraf S, Verma A, Jain A, Bidla P, Raikwar S Curr Drug Targets. 2024; 25(14):934-952.

PMID: 39257155 DOI: 10.2174/0113894501314558240822082557.

Vitamin K2 in Health and Disease: A Clinical Perspective.

Zhang T, OConnor C, Sheridan H, Barlow J Foods. 2024; 13(11).

PMID: 38890875 PMC: 11172246. DOI: 10.3390/foods13111646.

The impact of gut bacteria producing long chain homologs of vitamin K on colorectal carcinogenesis.

Smajdor J, Jedlinska K, Porada R, Gorska-Ratusznik A, Policht A, Srottek M Cancer Cell Int. 2023; 23(1):268.

PMID: 37950262 PMC: 10638769. DOI: 10.1186/s12935-023-03114-2.

Neferine Targets the Oncogenic Characteristics of Androgen-Dependent Prostate Cancer Cells via Inducing Reactive Oxygen Species.

Dasari S, Pathak N, Thomas A, Bitla S, Kumar R, Munirathinam G Int J Mol Sci. 2023; 24(18).

PMID: 37762540 PMC: 10532349. DOI: 10.3390/ijms241814242.

References

Otsuka M, Kato N, Shao R, Hoshida Y, Ijichi H, Koike Y . Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation. Hepatology. 2004; 40(1):243-51. DOI: 10.1002/hep.20260. View

Chen C, Welsbie D, Tran C, Baek S, Chen R, Vessella R . Molecular determinants of resistance to antiandrogen therapy. Nat Med. 2004; 10(1):33-9. DOI: 10.1038/nm972. View

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(5):1348-58. DOI: 10.3945/ajcn.2009.28691. View

Bindukumar B, Schwartz S, Nair M, Aalinkeel R, Kawinski E, Chadha K . Prostate-specific antigen modulates the expression of genes involved in prostate tumor growth. Neoplasia. 2005; 7(3):241-52. PMC: 1501136. DOI: 10.1593/neo.04529. View

Duan F, Yu Y, Guan R, Xu Z, Liang H, Hong L . Vitamin K2 Induces Mitochondria-Related Apoptosis in Human Bladder Cancer Cells via ROS and JNK/p38 MAPK Signal Pathways. PLoS One. 2016; 11(8):e0161886. PMC: 5003392. DOI: 10.1371/journal.pone.0161886. View

Shetty A, Dasari S, Banerjee S, Gheewala T, Zheng G, Chen A . Hepatoma-derived growth factor: A survival-related protein in prostate oncogenesis and a potential target for vitamin K2. Urol Oncol. 2016; 34(11):483.e1-483.e8. PMC: 5604255. DOI: 10.1016/j.urolonc.2016.05.027. View

Wang C, Youle R . The role of mitochondria in apoptosis*. Annu Rev Genet. 2009; 43:95-118. PMC: 4762029. DOI: 10.1146/annurev-genet-102108-134850. View

Shao C, Ahmad N, Hodges K, Kuang S, Ratliff T, Liu X . Inhibition of polo-like kinase 1 (Plk1) enhances the antineoplastic activity of metformin in prostate cancer. J Biol Chem. 2014; 290(4):2024-33. PMC: 4303657. DOI: 10.1074/jbc.M114.596817. View

Dasari S, Ali S, Zheng G, Chen A, Dontaraju V, Bosland M . Vitamin K and its analogs: Potential avenues for prostate cancer management. Oncotarget. 2017; 8(34):57782-57799. PMC: 5593683. DOI: 10.18632/oncotarget.17997. View

10.

Dreher T, Zentgraf H, Abel U, Kappeler A, Michel M, Bleyl U . Reduction of PTEN and p27kip1 expression correlates with tumor grade in prostate cancer. Analysis in radical prostatectomy specimens and needle biopsies. Virchows Arch. 2004; 444(6):509-17. DOI: 10.1007/s00428-004-1004-6. View

11.

Depowski P, Rosenthal S, Ross J . Loss of expression of the PTEN gene protein product is associated with poor outcome in breast cancer. Mod Pathol. 2001; 14(7):672-6. DOI: 10.1038/modpathol.3880371. View

12.

Hoimes C, Kelly W . Redefining hormone resistance in prostate cancer. Ther Adv Med Oncol. 2010; 2(2):107-123. PMC: 2883184. DOI: 10.1177/1758834009356433. View

13.

Nimptsch K, Rohrmann S, Linseisen J . Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr. 2008; 87(4):985-92. DOI: 10.1093/ajcn/87.4.985. View

14.

Monami G, Emiliozzi V, Bitto A, Lovat F, Xu S, Goldoni S . Proepithelin regulates prostate cancer cell biology by promoting cell growth, migration, and anchorage-independent growth. Am J Pathol. 2009; 174(3):1037-47. PMC: 2665763. DOI: 10.2353/ajpath.2009.080735. View

15.

Huang H, Cheville J, Pan Y, Roche P, Schmidt L, Tindall D . PTEN induces chemosensitivity in PTEN-mutated prostate cancer cells by suppression of Bcl-2 expression. J Biol Chem. 2001; 276(42):38830-6. DOI: 10.1074/jbc.M103632200. View

16.

Otera H, Ohsakaya S, Nagaura Z, Ishihara N, Mihara K . Export of mitochondrial AIF in response to proapoptotic stimuli depends on processing at the intermembrane space. EMBO J. 2005; 24(7):1375-86. PMC: 1142539. DOI: 10.1038/sj.emboj.7600614. View

17.

Tamori A, Habu D, Shiomi S, Kubo S, Nishiguchi S . Potential role of vitamin K(2) as a chemopreventive agent against hepatocellular carcinoma. Hepatol Res. 2007; 37 Suppl 2:S303-7. DOI: 10.1111/j.1872-034X.2007.00202.x. View

18.

Lamson D, Plaza S . The anticancer effects of vitamin K. Altern Med Rev. 2003; 8(3):303-18. View

19.

Tokita H, Tsuchida A, Miyazawa K, Ohyashiki K, Katayanagi S, Sudo H . Vitamin K2-induced antitumor effects via cell-cycle arrest and apoptosis in gastric cancer cell lines. Int J Mol Med. 2006; 17(2):235-43. View

20.

Samykutty A, Shetty A, Dakshinamoorthy G, Kalyanasundaram R, Zheng G, Chen A . Vitamin k2, a naturally occurring menaquinone, exerts therapeutic effects on both hormone-dependent and hormone-independent prostate cancer cells. Evid Based Complement Alternat Med. 2013; 2013:287358. PMC: 3767046. DOI: 10.1155/2013/287358. View