Alternative Therapeutic Approach to Renal-Cell Carcinoma: Induction of Apoptosis with Combination of Vitamin K<sub>3</sub> and D-fraction

Degen, Michael; Alexander, Bobby; Choudhury, Muhammad; Eshghi, Majid; Konno, Sensuke

doi:10.1089/end.2013.0207

Cited by 12 publications

(12 citation statements)

References 22 publications

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“…It can impair mitochondrial DNA replication and repair by inhibiting DNA polymerase gamma and induce reactive oxygen species-mediated apoptosis in human cancer cells 66 . Moreover, menadione has been shown to induce G2/M arrest in gastric cancer cells 67 and G1 arrest in renal cell carcinoma 68 . This is consistent with the enrichment of DNA replication and repair and cell cycle-related pathways in proteins upregulated in EC.…”

Section: Discussionmentioning

confidence: 99%

Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting

Liu

Xie

et al. 2021

Nat Commun

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Esophageal cancer (EC) is a type of aggressive cancer without clinically relevant molecular subtypes, hindering the development of effective strategies for treatment. To define molecular subtypes of EC, we perform mass spectrometry-based proteomic and phosphoproteomics profiling of EC tumors and adjacent non-tumor tissues, revealing a catalog of proteins and phosphosites that are dysregulated in ECs. The EC cohort is stratified into two molecular subtypes—S1 and S2—based on proteomic analysis, with the S2 subtype characterized by the upregulation of spliceosomal and ribosomal proteins, and being more aggressive. Moreover, we identify a subtype signature composed of ELOA and SCAF4, and construct a subtype diagnostic and prognostic model. Potential drugs are predicted for treating patients of S2 subtype, and three candidate drugs are validated to inhibit EC. Taken together, our proteomic analysis define molecular subtypes of EC, thus providing a potential therapeutic outlook for improving disease outcomes in patients with EC.

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Section: Discussionmentioning

confidence: 99%

Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting

Liu

Xie

et al. 2021

Nat Commun

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“…Pro-vitamin K3 inhibits CDK1 and CDK2 by their hyperphosphorylation, modification of the active sites of both proteins and abolishing the dephosphorylating activity of the enzymes. The anticancer effect of vitamin K2 and pro-vitamin K3 is most likely through regulation of p21 gene [69] , [70] .…”

Section: Redox-modulating Effect Of Vitamin K and Anticancer Activitymentioning

confidence: 99%

Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect

et al. 2018

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This review is directed to the redox-modulating properties and anticancer effect of vitamin K. The concept is focused on two aspects: (i) redox-cycle of vitamin K and its effect on the calcium homeostasis, “oncogenic” and “onco-suppressive” reactive oxygen species and the specific induction of oxidative stress in cancer; (ii) vitamin K plus C as a powerful redox-system, which forms a bypass between mitochondrial complexes II and III and thus prevents mitochondrial dysfunction, restores oxidative phosphorylation and aerobic glycolysis, modulates the redox-state of endogenous redox-pairs, eliminates the hypoxic environment of cancer cells and induces cell death. The analyzed data suggest that vitamin C&K can sensitize cancer cells to conventional chemotherapy, which allows achievement of a lower effective dose of the drug and minimizing the harmful side-effects. The review is intended for a wide audience of readers - from students to specialists in the field.

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“…More recently, increasing evidence shows that D-Fraction also exhibits immune-independent antitumoral effects on some types of cancer. Thus, the proteoglucan has antiproliferative or cytotoxic effect on PC3 (prostate cancer) [ 22 ], T24 (bladder cancer), HepG2 (liver cancer), U89 (brain cancer), HL60 (leukemia) [ 23 ], MCF7 and LM3 (breast cancer) [ 23 – 25 ], ACHN cells (kidney cancer) [ 26 , 27 ] and three canine cancer cell lines, but it does not affect the viability of A549 (lung cancer) and AGS cells (gastric cancer) [ 28 ].…”

Section: Introductionmentioning

confidence: 99%

Antitumoral and antimetastatic activity of Maitake D-Fraction in triple-negative breast cancer cells

et al. 2018

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Triple-negative breast cancer (TNBC) is associated with poor prognosis, high local recurrence rate and high rate of metastasis compared with other breast cancer subtypes. In addition, TNBC lacks a targeted therapy. This scenario highlights the need for novel compounds with high potential for TNBC treatment. In this regard, natural products are important sources of anticancer drugs. D-Fraction, a proteoglucan extracted from the edible and medicinal mushroom Grifola frondosa (Maitake), is a dietary supplement that has been shown to exert both immunostimulatory and immune-independent antitumoral effects on some cancer types. However, its antitumoral potential in TNBC is unknown. Therefore, we employed TNBC cells to investigate if D-Fraction is able to attenuate their aggressive phenotype. We found that D-Fraction decreases MDA-MB-231 cell viability through apoptosis induction and reduces their metastatic potential. D-Fraction increases cell-cell adhesion by increasing E-cadherin protein levels and β-catenin membrane localization, and increases cell-substrate adhesion. D-Fraction also decreases cell motility by affecting actin cytoskeleton rearrangements, and proteolytic activity of MMP-2 and MMP-9. Furthermore, D-Fraction decreases the invasive capacity of MDA-MB-231 cells. In concordance, D-Fraction retards tumor growth and reduces lung metastases in a xenograft model. Altogether, these results suggest the potential therapeutic role of D-Fraction in aggressive TNBC.

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Alternative Therapeutic Approach to Renal-Cell Carcinoma: Induction of Apoptosis with Combination of Vitamin K₃ and D-fraction

Cited by 12 publications

References 22 publications

Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting

Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting

Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect

Antitumoral and antimetastatic activity of Maitake D-Fraction in triple-negative breast cancer cells

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Alternative Therapeutic Approach to Renal-Cell Carcinoma: Induction of Apoptosis with Combination of Vitamin K3 and D-fraction

Cited by 12 publications

References 22 publications

Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting

Large-scale and high-resolution mass spectrometry-based proteomics profiling defines molecular subtypes of esophageal cancer for therapeutic targeting

Vitamin K: Redox-modulation, prevention of mitochondrial dysfunction and anticancer effect

Antitumoral and antimetastatic activity of Maitake D-Fraction in triple-negative breast cancer cells

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Alternative Therapeutic Approach to Renal-Cell Carcinoma: Induction of Apoptosis with Combination of Vitamin K₃ and D-fraction