Table 1.
Preclinical studies of vitamins A, C, E, and D.
| Form of the vitamin | Type of cancer | Model of the study | Mechanism of action | References | ||
|---|---|---|---|---|---|---|
| Vitamin A | All-trans retinoic acid | Breast cancer | In vitro (MCF-7 cells) | ↓expression of PPARγ | (74) | |
| ↑stimulation of DOK1/PPARγ pathways | ||||||
| ↓ cell proliferation | ||||||
| Synthetic retinoid | Breast cancer | In vitro (MCF-7 and MDA-MB-231) | ↓ Wnt/−catenin signaling pathway | (75) | ||
| ↓ cell proliferation and differentiation | ||||||
| All-trans retinoic acid | Lung cancer | In vitro (Huh-7 cells) | ↑ survival rate | (76) | ||
| In vivo (SPHK1 knockout mice and SPHK1 transgenic mice) | ↓ tumor progression | |||||
| All-trans retinoic acid | Gastric cancer | In vitro (Human GC cell lines, AGS and MKN-45) | ↓ cell viability | (77) | ||
| ↑ caspases | ||||||
| ↑ apoptosis | ||||||
| All-trans-RA-Podophyllotoxin | Gastric cancer | In vitro (MKN-45 and BGC-823) | ↓ cell growth | (78) | ||
| ↓ ERK1/2 and AKT signaling pathways | ||||||
| ↑ apoptosis | ||||||
| Polyinosinic-polycytidylic acid/ 13-cis-retinoic acid | Neuroblastoma | In vitro [(SK-N-AS) (CRL-2137), SK-N-FI (CRL-2142), SK-N-DZ (CRL-2149), and BE(2)-M17 (CRL-2267)] | ↑ stimulation of retinoic acid receptors beta (RAR-β) | (82) | ||
| In vivo (nonobese diabetic/SCID) (NOD/SCID, NOD.CB17-Prkdcscid/NcrCrl) mice | ↓ vessel formation | |||||
| all-trans-RA | Cervical cancer | In vivo (BALB/c mice model) | ↓ MDSC | (79) | ||
| ↑ CD + 8 T cells | ||||||
| ↓ tumor growth | ||||||
| all-trans-RA | Hepatocellular carcinoma | In vitro (HepG2, Hepa1-6 and H22 hepatoma carcinoma cell line) | ↓ MDSC | (80) | ||
| In vivo (C57BL/6 N mice with Hepa1-6 tumor) | ↓ tumor-associated macrophages | |||||
| ↓ arginase 1, iNOS, IDO, S100A8 + A9 | ||||||
| all-trans-RA | Breast cancer | In vivo (4 T1 mouse model of breast cancer) | ↑ mouse long-term survival rates | (81) | ||
| ↑ cytotoxicity of CD8+ T cells and natural killer cells | ||||||
| Vitamin C | Breast cancer | In vitro (MCF10A, MDA-MB-231, MCF-7, and SK-BR-3) | ↓ cell viability | (90) | ||
| Brain cancer | In vitro [human glioblastoma DBTRG and human renal tubular epithelial (HK-2)] | ↓ cell viability | (93) | |||
| Oral cancer | In vitro (human OSCC-derived cell lines CAL27, SCC9, and SCC25) | ↑ ROS level | (94) | |||
| ↓ Bcl-2 | ||||||
| ↑ Bax expression, caspases | ||||||
| ↑ cell cycle arrest at the G0/G1 phase | ||||||
| Colorectal cancer, breast cancer, melanoma, pancreatic cancer | In vivo (C57BL/6 J, BALB/c, FVB, and NOD-SCID mice) | ↓ tumor growth | (96) | |||
| ↑ CD8 T cells activity | ||||||
| Ascorbate | Lymphoma | In vitro (DLBCL cell line OC-LY1) | ↑ TET activity | (104) | ||
| ↑ expression of tumor suppressor genes | ||||||
| ↑ chemosensitivity | ||||||
| Ascorbate | Leukemia | In vivo (Vav-tTA (VTA) transgenic mice) | ↑ DNA demethylation | (105) | ||
| ↑ TET2 restoration phenotypes | ||||||
| Ascorbate | Thyroid cancer | In vitro (FTC133 and 8305c) | ↓ expression of HIF1α and GLUT1 | (108) | ||
| Vitamin E | β-tocotrienol | Prostate cancer and lung cancer | In vitro (Mouse Lewis lung cancer (LLC) cells, DU145 human prostate cancer cells and Jurkat T cells) | ↓ PD-L1 expression | (118) | |
| In vivo | ↓ JAK2/STAT3 pathway | |||||
| δ-tocotrienol | Prostate cancer | In vitro (DU145 and PC3) | ↑ ROS | (120) | ||
| ↑ apoptosis | ||||||
| Tocotrienol/6-O-carboxypropyl-α-tocotrienol | Malignant mesothelioma |
In vitro (H2052 cell line) In vivo (ICR mice) |
↓ tumor size | (122) | ||
| Tocopherol/ tocopherol succinate | Breast cancer | In vitro (MDA-MB-231 and MDA-MB-468) | ↓ cell growth | (123) | ||
| Annatto tocotrienol/γ-tocotrinol/ δ-tocotrienol | Chondrosarcoma | In vitro (Human chondrosarcoma SW1353 cells) | ↑ G1 arrest | (125) | ||
| ↑ apoptosis | ||||||
| (RRR-α-tocopherol [αT], RRR-γ-tocopherol [γT]) | Breast cancer | In vitro (human MDA-MB-435, MCF-7, and murine 66 cL-4 mammary cancer cells) | ↑ caspases-8 and -9 | (117) | ||
| ↓ c-FLIP and surviving | ||||||
| ↑ apoptosis | ||||||
| ↓ colony formation | ||||||
| Synthetic forms (all-rac-α-tocopherol [all-rac-αT], all-rac-α-tocopheryl acetate [all-rac-αTAc]) | In vivo (BALB/c mouse mammary cancer model) | ↓ tumor growth | ||||
| ↓ metastasis | ||||||
| Vitamin D | 1,25(OH)2-D3 | Prostate cancer | In vitro (C4-2 cells and CWR22 cells) | ↑ tumor regression | (135) | |
| in vivo (athymic nude (Hsd:Athymic Nude-Foxn1nu) mice) | ↓ LSD1 | |||||
| 1,25-dihydroxycholecalciferol | Breast cancer | In vitro | ↑ tumor regression | (136) | ||
| In vivo (MMTV-polyoma middle T antigen (PyMT) transgenic mice) | ↓ lung metastasis | |||||
| ↓ Ki-67, cyclin D1, and ErbB2 levels | ||||||
| Calcitriol | Colon cancer | In vitro (HT29 and Caco-2 cells) | ↑ cell cycle arrest | (137) | ||
| ↑ expression of cell cycle regulators p21 and p27 | ||||||
| ↑ activation of JNK1 | ||||||
| 1,25-dihydroxyvitamin D (1,25(OH)2D) | Bone cancer | In vitro (Human MG-63 osteosarcoma cells) | ↓ mTORC1 | (138) | ||
| ↓ ROS | ||||||
| 1,25(OH)2D3 | Gastric cancer | In vitro (Human GC cells MKN45, MKN28, and KATO III) | ↓ CD44 | (139) | ||
| In vivo (orthotopic GC nude mice model) | ↓ Wnt/β-catenin signaling pathway |