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

 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]