Table 4.
aVitamins change PI3K/Akt and/or GSK3 activities
| 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). | [79–81] |
| 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. | [132–134] |
| 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. | [140–142] |
| 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. | [146–148] |
| 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] |
aVitamins: not all the vitamins are widely accepted as vitamins, b APP/PS1 amyloid precursor protein/presenilin-1, c Hca2 niacin receptor 1