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Table 4 aVitamins change PI3K/Akt and/or GSK3 activities

From: Chronic over-nutrition and dysregulation of GSK3 in diseases

Vitamins Model system Observed effects Ref.
 Vitamin A Mouse embryonic stem cells, human neuroblastoma cells, human bronchial epithelium. PI3K via IGF-1 receptor/IRS1; suppress cyclin D1 protein expression via GSK3, stage ≥ 1 of the kinase insensitivity (Table 1). [7981]
 Vitamin B1 analog Mice with diabetes, mouse cadiomyocytes, human embryonic kidney cells, bAPP/PS1 mice. Activate Akt, preventing diabetes-induced diastolic dysfunction and heart failure; avert high glucose-induced β-amyloid related to GSK3 activity; inhibit GSK3 activity to subdue cognitive damages and beta-amyloid accumulation. [132134]
 Vitamin B3 (Niacin) and  vitamin B6 (pyridoxine) Human epidermoid carcinoma cells, Chinese hamster ovary cells, cHca2 +/− mice, human platelets. Augment PI3K/Akt activities. [135, 136]
 Vitamin B8 (inositol) Smokers. Suppress Akt and ERK. [137]
 Vitamin B9 (folic acid) Mouse neural stem cells. Stimulate cell growth by modification of epigenetics of PI3K/Akt/cAMP response element-binding protein pathway. [138]
 Vitamin B10  (para- aminobenzoic acid) Zebrafish embryos. Raise pSGSK3β reduced by valproic acid, an anti-epilepic drug). [139]
 Vitamin B11 (salicylic acid) Human umbilical vein endothelial cells and human foreskin fibroblasts, murine myoblasts, Humans with inflammation. Inhibit COX-2 gene transcription, resulting in anti-inflammatory effects. [140142]
 Vitamin B13 (orotic acid) Human umbilical vein endothelial cells, SD rats. Patients with orotic acid metabolic disorders may reduce insulin response and PI3K/Akt signaling, generating insulin resistance. [143]
 Vitamin B14 Human bone marrows. Increase cell growth and haemopoiesis. [144]
 Vitamin B17 (amygdalin) Human bladder cancer cells. Inhibit cell growth via activated Akt-related pathways. [145]
 Pyrroloquinoline quinine Rat cardiomyocytes, hippocampal neurons and brain cortex from SD rats. Possibly naturally existing in vitamin B complexes can activate PI3K/Akt and reduce cell apoptosis or inhibits GSK3β activity in nervous tissues of glutamate-injected animals. [146148]
 Vitamin C or vitamin E Human colon cancer cells. Inhibit casein kinase 2 (CKII) downregulation-mediated aging in cells, whereas suppression of CKII raises PI3K/Akt activities. [149]
 Vitamin C Human breast cancer cells. Enhance a synthetic anti-cancer drug, mitoxantrone-induced cytotoxicity. [150]
 Vitamin D   Vitamin D receptor mediates PI3K/Akt activation; vitamin D reduces caspase activities for cell apoptosis via vitamin D receptor/PI3K/Akt pathway. [151, 152]
Human myeloid leukaemic cells, rat osteoblasts. Vitamin D deficiency induces hyperinsulinemia and insulin resistance in obese mice. [153]
C57BL/6J mice. Enhance effects of PI3K inhibitors on cell growth. [154]
Human prostate cancer cells. Induce the tolerance or immunosuppression through the PI3K/Akt pathway. [155, 156]
Human monocyte-derived tolerogenic dendritic cells, human CD3+ T cells. Activate MAP kinase and/or PI3K/Akt for protecting cell death.  
 Vitamin E Cultured mouse cortical neurons, human neuroblastoma.   [157, 158]
Human breast cancer cells, human prostate cancer cells. Tocotrienols (natural forms of vitamin E) or tocopherol (the saturated form of vitamin E)-associated protein can suppress cancer growth via inhibition of PI3K. [75, 76]
Mouse neoplastic mammary epithelial cells. Gamma-tocotrienol can block human epidermal growth factor receptor 3-dependent PI3K/Akt mitogenic signaling. [77]
 Vitamin J (catechol) Mouse microglial cells. Iridoid and catechol (vitamin J) derivatives of natural products, have anti-inflammatory activities via inhibition of the PI3K/Akt and p38 pathways. [159]
 Vitamin K Apoptotic cells. Protein Gas6 and S are vitamin K dependent proteins and ligands of RTK that can regulate PI3K/Akt pathway. [160]
 Vitamin P Mouse primary neurons. Increase PI3K/Akt activities and the survival of motoneurons via tropomyosin-receptor kinase B. [161]
 Vitamin U Mice, rats. Vitamin U (methylmethioninesulfonium chloride) reduces capillaries’ permeability of animal skin; protecting gastric mucosa from lesion caused by aspirin, an acetylated form of salicylic acid (vitamin B11) with anti-inflammatory effects. [162]
  1. aVitamins: not all the vitamins are widely accepted as vitamins, b APP/PS1 amyloid precursor protein/presenilin-1, c Hca2 niacin receptor 1