InterPAD - DETAILS

Acid, Ascorbic, Acid, L-Ascorbic, Ascorbate, Ferrous, Ascorbate, Magnesium, Ascorbate, Sodium, Ascorbic Acid, Ascorbic Acid, Monosodium Salt, di-L-Ascorbate, Magnesium, Ferrous Ascorbate, Hybrin, L Ascorbic Acid, L-Ascorbic Acid, Magnesium Ascorbate, Magnesium Ascorbicum, Magnesium di L Ascorbate, Magnesium di-L-Ascorbate, Magnorbin, Sodium Ascorbate, Vitamin C

No.	Title	Href
1	Vitamin C Sensitizes Melanoma to BET Inhibitors. Cancer Res. 2018 Jan 15;78(2):572-583. doi: 10.1158/0008-5472.CAN-17-2040.	`Click`
2	Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway. Oxid Med Cell Longev. 2022 Jul 19;2022:5361241. doi: 10.1155/2022/5361241.	`Click`
3	High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model. Proc Natl Acad Sci U S A. 2020 Jan 21;117(3):1666-1677. doi: 10.1073/pnas.1908158117.	`Click`
4	Anti-neoplastic action of Cimetidine/Vitamin C on histamine and the PI3K/AKT/mTOR pathway in Ehrlich breast cancer. Sci Rep. 2022;12(1):11514. Published 2022 Jul 7. doi:10.1038/s41598-022-15551-6	`Click`
5	Synergistic enhancement of topotecan-induced cell death by ascorbic acid in human breast MCF-7 tumor cells. Free Radic Biol Med. 2017 Dec;113:406-412. doi: 10.1016/j.freeradbiomed.2017.10.377	`Click`
6	Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways. Oncol Rep. 2017 Apr;37(4):2177-2184. doi: 10.3892/or.2017.5439.	`Click`
7	Pharmacological Ascorbate Suppresses Growth of Gastric Cancer Cells with GLUT1 Overexpression and Enhances the Efficacy of Oxaliplatin Through Redox Modulation. Theranostics. 2018 Feb 2;8(5):1312-1326. doi: 10.7150/thno.21745.	`Click`
8	Combination of Vitamin C and Lenvatinib potentiates antitumor effects in hepatocellular carcinoma cells in vitro. PeerJ. 2023 Jan 25;11:e14610. doi: 10.7717/peerj.14610.	`Click`
9	Vitamin C Improves the Inhibitory Effects of Oxaliplatin on HCT-116 Colorectal Cancer Growth and Progression Through Cellular Oxidant Function-associated Cadherin Molecules. Anticancer Res. 2023 Oct;43(10):4461-4472. doi: 10.21873/anticanres.16641.	`Click`
10	Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin. Pharmacol Res Perspect. 2020 Aug;8(4):e00632. doi: 10.1002/prp2.632.	`Click`

No.

Title

Href

Vitamin C Sensitizes Melanoma to BET Inhibitors. Cancer Res. 2018 Jan 15;78(2):572-583. doi: 10.1158/0008-5472.CAN-17-2040.

Click

Vitamin C Sensitizes Pancreatic Cancer Cells to Erastin-Induced Ferroptosis by Activating the AMPK/Nrf2/HMOX1 Pathway. Oxid Med Cell Longev. 2022 Jul 19;2022:5361241. doi: 10.1155/2022/5361241.

Click

High-dose ascorbic acid synergizes with anti-PD1 in a lymphoma mouse model. Proc Natl Acad Sci U S A. 2020 Jan 21;117(3):1666-1677. doi: 10.1073/pnas.1908158117.

Click

Anti-neoplastic action of Cimetidine/Vitamin C on histamine and the PI3K/AKT/mTOR pathway in Ehrlich breast cancer. Sci Rep. 2022;12(1):11514. Published 2022 Jul 7. doi:10.1038/s41598-022-15551-6

Click

Synergistic enhancement of topotecan-induced cell death by ascorbic acid in human breast MCF-7 tumor cells. Free Radic Biol Med. 2017 Dec;113:406-412. doi: 10.1016/j.freeradbiomed.2017.10.377

Click

Combined treatment with vitamin C and methotrexate inhibits triple-negative breast cancer cell growth by increasing H2O2 accumulation and activating caspase-3 and p38 pathways. Oncol Rep. 2017 Apr;37(4):2177-2184. doi: 10.3892/or.2017.5439.

Click

Pharmacological Ascorbate Suppresses Growth of Gastric Cancer Cells with GLUT1 Overexpression and Enhances the Efficacy of Oxaliplatin Through Redox Modulation. Theranostics. 2018 Feb 2;8(5):1312-1326. doi: 10.7150/thno.21745.

Click

Combination of Vitamin C and Lenvatinib potentiates antitumor effects in hepatocellular carcinoma cells in vitro. PeerJ. 2023 Jan 25;11:e14610. doi: 10.7717/peerj.14610. 

Click

Vitamin C Improves the Inhibitory Effects of Oxaliplatin on HCT-116 Colorectal Cancer Growth and Progression Through Cellular Oxidant Function-associated Cadherin Molecules. Anticancer Res. 2023 Oct;43(10):4461-4472. doi: 10.21873/anticanres.16641.

Click

Ascorbate sensitizes human osteosarcoma cells to the cytostatic effects of cisplatin. Pharmacol Res Perspect. 2020 Aug;8(4):e00632. doi: 10.1002/prp2.632.

Click

Name	Vitamin C
PubChem CID	54670067
Molecular Weight	176.12g/mol
Synonyms	Acid, Ascorbic, Acid, L-Ascorbic, Ascorbate, Ferrous, Ascorbate, Magnesium, Ascorbate, Sodium, Ascorbic Acid, Ascorbic Acid, Monosodium Salt, di-L-Ascorbate, Magnesium, Ferrous Ascorbate, Hybrin, L Ascorbic Acid, L-Ascorbic Acid, Magnesium Ascorbate, Magnesium Ascorbicum, Magnesium di L Ascorbate, Magnesium di-L-Ascorbate, Magnorbin, Sodium Ascorbate, Vitamin C
Formula	C₆H₈O₆
SMILES	C(C(C1C(=C(C(=O)O1)O)O)O)O
InChI	1S/C6H8O6/c7-1-2(8)5-3(9)4(10)6(11)12-5/h2,5,7-10H,1H2/t2-,5+/m0/s1
InChIKey	CIWBSHSKHKDKBQ-JLAZNSOCSA-N
CAS Number	50-81-7
ChEMBL ID	CHEMBL40274
ChEBI ID	CHEBI:29073
Drug Bank ID	DB00126
KEGG ID	C00072
Toxicity	Organism	Test Type	Route(Dose)
	rat	LD50	intraperitoneal(165 mg/kg)
	mouse	LD50	intraperitoneal(254 mg/kg)
	rat	LD50	oral(322 mg/kg)
Structure			Download 2D MOL 3D MOL

Chineses Pinyin	FuPenZi
Use Part	Aggregate Fruit
Habitat	AnHui, JiangSu, ZheJiang
Flavor	Sweet, Sour
Meridian Tropism	Liver, Kidney, Bladder
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Rosales 　　　　-->Family: Rosaceae 　　　　　-->Genus: Rubus 　　　　　　-->Species: Rubus chingii

Chineses Pinyin	LaMu
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Brassicales 　　　　-->Family: Moringaceae 　　　　　-->Genus: Moringa 　　　　　　-->Species: Moringa oleifera

Pair Name	Vitamin C, Erastin
Partner Name	Erastin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Ferroptosis
Gene Regulation	Down-regulation	Expression	CP	hsa1356
	Up-regulation	Expression	HMOX1	hsa3162
	Up-regulation	Expression	NCOA4	hsa8031
	Up-regulation	Expression	NFE2L2	hsa4780
	Up-regulation	Expression	NFE2L2	hsa4780
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
	Up-regulation	Expression	SLC2A1	hsa6513
	Down-regulation	Expression	SLC7A11	hsa23657
In Vitro Model	PaTu 8988s	Pancreatic adenocarcinoma	Homo sapiens (Human)	CVCL_1846
In Vitro Model	BxPC-3	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0186
In Vivo Model	Panc02 cells (1×10⁵ cells/site) were transfected and subcutaneously injected into 4-week-old C57BL/6 mice to generate xenografts.
Result	The combination of erastin and vitamin C exerts a synergistic effect of classical and nonclassical modes to induce ferroptosis in PC cells, which may provide a promising therapeutic strategy for PC.

Pair Name	Vitamin C, Anti-PD-1 antibody
Partner Name	Anti-PD-1 antibody
Disease Info	[ICD-11: 2B33.5]	Lymphoma		Investigative
Biological Phenomena	Inhibition-->Anti-PD1 checkpoint
Gene Regulation	Up-regulation	Expression	GZMB	hsa3002
Gene Regulation	Up-regulation	Expression	IL12B	hsa3593
In Vitro Model	A20	Reticulum cell sarcoma	Mus musculus (Mouse)	CVCL_1940
	SU-DHL-6	Diffuse large B-cell lymphoma germinal center B-cell type	Homo sapiens (Human)	CVCL_2206
	OCI-Ly1	Diffuse large B-cell lymphoma	Homo sapiens (Human)	CVCL_1879
	OCI-Ly7	Diffuse large B-cell lymphoma germinal center B-cell type	Homo sapiens (Human)	CVCL_1881
	OCI-Ly3	Diffuse large B-cell lymphoma activated B-cell type	Homo sapiens (Human)	CVCL_8800
In Vivo Model	40 BALB/c mice received a subcutaneous (s.c.) right flank injection of 5×10⁶ A20 tumor cells in phosphate-buffered saline (PBS) and were randomly assigned to 4 groups of 10 mice: vehicle, anti-PD1 (α-PD1), AA, and AA+α-PD1.
Result	This study shows that AA treatment 1) increases immunogenicity of lymphoma cells; 2) enhances intratumoral infiltration of CD8+ T cells and macrophages; and 3) synergizes with anti-PD1 checkpoint inhibition in a syngeneic lymphoma mouse model via marked activation of cytotoxic cells (cytotoxic T cells and NK cells) and antigen presenting cells. The data provide a compelling rationale for testing combinations of high-dose AA and anti-PD1 agents in patients with aggressive B cell lymphoma and in preclinical models of other malignancies.

Pair Name	Vitamin C, Cimetidine
Partner Name	Cimetidine
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Inhibition-->Angiogenesis
Gene Regulation	Down-regulation	Phosphorylation	AKT1	hsa207
	Up-regulation	Expression	CASP3	hsa836
	Down-regulation	Phosphorylation	MTOR	hsa2475
	Down-regulation	Phosphorylation	PIK3CA	hsa5290
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
In Vivo Model	Each mouse in the experimental group received 0.2 mL EAC saline solution (2.5×10⁶ cells) subcutaneously in the mammary fat pad on day 0. Mice were left for 9 days with free access to water and food to develop solid breast cancer.
Result	We concluded that the synergistic combination provided a promising anti-neoplastic effect via reducing the angiogenesis, oxidative stress, increasing apoptosis,as well as inhibiting the activation of PI3K/AKT/mTOR cue, and suggesting its use as a treatment option for breast cancer.

Pair Name	Vitamin C, Topotecan
Partner Name	Topotecan
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->DNA damage
Gene Regulation	Up-regulation	Expression	CDKN1A	hsa1026
	Up-regulation	Expression	H2AX	hsa3014
	Up-regulation	Expression	TP53	hsa7157
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Synergistic enhancement of topotecan-induced cell death by ascorbic acid in human breast MCF-7 tumor cells.

Pair Name	Vitamin C, Methotrexate
Partner Name	Methotrexate
Disease Info	[ICD-11: 2C60]	Breast cancer		Investigative
Biological Phenomena	Induction-->Blockade of cell cycle in G2/M phase
Gene Regulation	Up-regulation	Cleavage	CASP3	hsa836
Gene Regulation	Up-regulation	Phosphorylation	MAPK14	hsa1432
In Vitro Model	MDA-MB-231	Breast adenocarcinoma	Homo sapiens (Human)	CVCL_0062
In Vitro Model	MCF-7	Invasive breast carcinoma of no special type	Homo sapiens (Human)	CVCL_0031
Result	Combined low-dose vitamin C and MTX had synergistic anti-proliferative/cytotoxic effects on TNBC cells. In addition, co-treatment increased H2O2 levels and activated both caspase-3 and p38 cell death pathways.

Pair Name	Vitamin C, Oxaliplatin
Partner Name	Oxaliplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer		Investigative
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
	Up-regulation	Activity	CASP7	hsa840
	Up-regulation	Expression	H2AX	hsa3014
	Down-regulation	Expression	SLC2A1	hsa6513
In Vitro Model	AGS	Gastric adenocarcinoma	Homo sapiens (Human)	CVCL_0139
	SGC-7901	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0520
	HGC-27	Gastric carcinoma	Homo sapiens (Human)	CVCL_1279
	MGC-803	Gastric mucinous adenocarcinoma	Homo sapiens (Human)	CVCL_5334
In Vivo Model	AGS cells (1×10⁷/mice) were subcutaneously inoculated into the right armpit of the nude mice.
Result	The current study showed that GLUT1 expression was inversely correlated with sensitivity of gastric cancer cells to pharmacological ascorbate and suggested that GLUT1 expression in gastric cancer may serve as a marker for sensitivity to pharmacological ascorbate.

Pair Name	Vitamin C, Lenvatinib
Partner Name	Lenvatinib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Biological Phenomena	Inhibition-->Cell proliferative, migratory and invasive capacities
Gene Regulation	Down-regulation	Expression	MET	hsa4233
In Vitro Model	Hep 3B2.1-7	Childhood hepatocellular carcinoma	Homo sapiens (Human)	CVCL_0326
	Huh-7	Adult hepatocellular carcinoma	Homo sapiens (Human)	CVCL_0336
	SK-HEP-1	Liver and intrahepatic bile duct epithelial neoplasm	Homo sapiens (Human)	CVCL_0525
Result	Combination of Vitamin C and Lenvatinib potentiates antitumor effects in hepatocellular carcinoma cells in vitro

Pair Name	Vitamin C, Cisplatin
Partner Name	Cisplatin
Disease Info	[ICD-11: 2B51]	Osteosarcoma		Investigative
Biological Phenomena	Induction-->Glycolysis
Gene Regulation	Up-regulation	Expression	G6PD	hsa2539
	Up-regulation	Expression	H2AX	hsa3014
	Up-regulation	Expression	HK2	hsa3099
	Up-regulation	Expression	MYC	hsa4609
	Up-regulation	Expression	ROS1	hsa6098
	Up-regulation	Expression	SLC16A4	hsa9122
In Vitro Model	143B	Osteosarcoma	Homo sapiens (Human)	CVCL_2270
In Vitro Model	U2OS	Osteosarcoma	Homo sapiens (Human)	CVCL_0042
Result	Our findings provide a rationale for combining cisplatin with ascorbate in therapeutic strategies against OS.

Pair Name	Vitamin C, GW841819X
Partner Name	GW841819X
Disease Info	[ICD-11: 2C30]	Melanoma		Investigative
Gene Regulation	Down-regulation	Expression	BRD4	hsa23476
	Down-regulation	Expression	H4C12	hsa8362
	Down-regulation	Expression	HAT1	hsa8520
	Down-regulation	Expression	HRH4	hsa59340
In Vitro Model	A2058	Amelanotic melanoma	Homo sapiens (Human)	CVCL_1059
	SK-MEL-28	Cutaneous melanoma	Homo sapiens (Human)	CVCL_0526
	SK-MEL-2	Melanoma	Homo sapiens (Human)	CVCL_0069
	C8161	Cutaneous melanoma	Homo sapiens (Human)	CVCL_6813
	1205Lu	Cutaneous melanoma	Homo sapiens (Human)	CVCL_5239
In Vivo Model	Mice were then engrafted on the neck by injecting 2×10⁵ mouse melanoma cells, B16-F10, to produce experimental tumor.
Result	This study shows that ascorbate can enhance the efficacy of BET inhibitors, providing a possible clinical solution to challenges arising in phase I trials from the dose-dependent side effects of this class of epigenetic therapy.