Anticancer activities of vitamin K3 analogues

Wellington, Kevin W.; Hlatshwayo, Vincent; Kolesnikova, Natasha I.; Saha, Sourav; Kaur, Mandeep; Motadi, Lesetja Raymond

doi:10.1007/s10637-019-00855-8

Cited by 22 publications

(17 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, VK3 and its analogs are potent inhibitors of cell proliferation on many cancer cell lines. They act as cellular redox mediators generating ROS and inducing apoptosis by mitochondrial pathway [197]. Combining VK3 with other molecules sharing structural similarity, such as plumbagin and juglone, naturally occurring naphthoquinones found in polyphenol-rich Juglans regia [198], or with vitamins or drugs that also function through modulation of intracellular redox states could potentiate the antitumor effects [199,200].…”

Section: The Effect Of Vitamin K On Cancermentioning

confidence: 99%

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

2021

View full text Add to dashboard Cite

As human life expectancy is rising, the incidence of age-associated diseases will also increase. Scientific evidence has revealed that healthy diets, including good fats, vitamins, minerals, or polyphenolics, could have antioxidant and anti-inflammatory activities, with antiaging effects. Recent studies demonstrated that vitamin K is a vital cofactor in activating several proteins, which act against age-related syndromes. Thus, vitamin K can carboxylate osteocalcin (a protein capable of transporting and fixing calcium in bone), activate matrix Gla protein (an inhibitor of vascular calcification and cardiovascular events) and carboxylate Gas6 protein (involved in brain physiology and a cognitive decline and neurodegenerative disease inhibitor). By improving insulin sensitivity, vitamin K lowers diabetes risk. It also exerts antiproliferative, proapoptotic, autophagic effects and has been associated with a reduced risk of cancer. Recent research shows that protein S, another vitamin K-dependent protein, can prevent the cytokine storm observed in COVID-19 cases. The reduced activation of protein S due to the pneumonia-induced vitamin K depletion was correlated with higher thrombogenicity and possibly fatal outcomes in COVID-19 patients. Our review aimed to present the latest scientific evidence about vitamin K and its role in preventing age-associated diseases and/or improving the effectiveness of medical treatments in mature adults ˃50 years old.

show abstract

Section: The Effect Of Vitamin K On Cancermentioning

confidence: 99%

The Role of Vitamin K in Humans: Implication in Aging and Age-Associated Diseases

2021

View full text Add to dashboard Cite

show abstract

“…Vit K3 is a quinone used with cancer chemotherapeutics. Vit K3 and its analogs have been showed anticancer activities in several types of cancer including prostate cancer, breast cancer, melanoma and liver cancer in vitro and in vivo (16,21,22). Although the main biological effects on cancers are attributed to its role in the redox cycle and arylating nucleophilic substrates, Vit K3 has been identified as a specific inhibitor of Siah2 that inhibits both arms of the Siah2 downstream signaling network, the Ras/ MAPK pathway and the hypoxic response pathway independent of reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

Targeting ADT-Induced Activation of the E3 Ubiquitin Ligase Siah2 to Delay the Occurrence of Castration-Resistant Prostate Cancer

et al. 2021

View full text Add to dashboard Cite

Siah2 is an E3 ubiquitin ligase that targets androgen receptor (AR) and plays an important role in the development of castration-resistant prostate cancer (CRPC). However, the regulation of Siah2 in prostate cancer (PCa) is largely unknown. In this study, we used AR-dependent and -independent cells lines to investigate the cellular roles of AR and androgen deprivation therapy (ADT) on Siah2 protein levels and E3 ligase activity using Western blotting and co-immunoprecipitation. We also validated our findings using patient samples taken before and after ADT. Finally, we used xenograft tumor models to test the effects of ADT combined with vitamin K3 (Vit K3) on tumor growth in vivo. Our results showed that AR stabilizes Siah2 protein by attenuating its self-ubiquitination and auto-degradation, likely by blocking its E3 ubiquitin ligase activity. Conversely, ADT decreased Siah2 protein expression but enhanced its E3 ligase activity in PCa cells. Notably, the findings that ADT decreasing Siah2 protein expression were verified in a series of paired PCa samples from the same patient. Additionally, we found that ADT-induced Siah2 activation could be abolished by Vit K3. Strikingly, ADT combined with Vit K3 treatment delayed the occurrence of CRPC and dramatically inhibited the growth of tumor xenografts compared with ADT treatment alone. AR is an inhibitor of Siah2 in PCa, and ADT leads to the continuous activation of Siah2, which may contribute to CRPC. Finally, ADT+Vit K3 may be a potential approach to delay the occurrence of CRPC.

show abstract

“…15 Reportedly, vitamin K3 exerts anti-cancer properties via cytostatic effects. 16,17 Vitamin K recycling Vitamin K serves as a cofactor for the enzyme g-glutamyl carboxylase (GGCX), which catalyzes conversion of the Glu residue of vitamin K-dependent proteins into g-carboxyglutamic acid (Gla; Figure 2). This process is driven by the oxidation of vitamin K-hydroquinone to vitamin K-epoxide in the vitamin K cycle, generating the possibility to introduce an extra carboxyl group at the g position of the glutamate residue, thereby adding an extra negative charge to the protein.…”

Section: Vitamin K Sources and Subformsmentioning

confidence: 99%