Ferroptosis Regulator Information

General Information of the Ferroptosis Regulator (ID: REG10478)
Regulator Name Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1)
Synonyms
ALDH3; ALDHIII; Aldehyde dehydrogenase 3; Aldehyde dehydrogenase family 3 member A1
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Gene Name ALDH3A1
Gene ID 218
Regulator Type Protein coding
Uniprot ID P30838
Sequence
MSKISEAVKRARAAFSSGRTRPLQFRIQQLEALQRLIQEQEQELVGALAADLHKNEWNAY
YEEVVYVLEEIEYMIQKLPEWAADEPVEKTPQTQQDELYIHSEPLGVVLVIGTWNYPFNL
TIQPMVGAIAAGNSVVLKPSELSENMASLLATIIPQYLDKDLYPVINGGVPETTELLKER
FDHILYTGSTGVGKIIMTAAAKHLTPVTLELGGKSPCYVDKNCDLDVACRRIAWGKFMNS
GQTCVAPDYILCDPSIQNQIVEKLKKSLKEFYGEDAKKSRDYGRIISARHFQRVMGLIEG
QKVAYGGTGDAATRYIAPTILTDVDPQSPVMQEEIFGPVLPIVCVRSLEEAIQFINQREK
PLALYMFSSNDKVIKKMIAETSSGGVAANDVIVHITLHSLPFGGVGNSGMGSYHGKKSFE
TFSHRRSCLVRPLMNDEGLKVRYPPSPAKMTQH

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Family Aldehyde dehydrogenase family
Function
ALDHs play a major role in the detoxification of alcohol- derived acetaldehyde (Probable). They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation (Probable). Oxidizes medium and long chain aldehydes into non-toxic fatty acids. Preferentially oxidizes aromatic aldehyde substrates. Comprises about 50 percent of corneal epithelial soluble proteins (By similarity). May play a role in preventing corneal damage caused by ultraviolet light (By similarity).

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HGNC ID
HGNC:405
KEGG ID hsa:218
Full List of the Ferroptosis Target of This Regulator and Corresponding Disease/Drug Response(s)
ALDH3A1 can regulate the following target(s), and cause disease/drug response(s). You can browse detail information of target(s) or disease/drug response(s).
Browse Target
Browse Disease
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Unspecific Target [Unspecific Target]
In total 2 item(s) under this target
Experiment 1 Reporting the Ferroptosis Target of This Regulator [1]
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Responsed Drug Oxyfedrine Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 DMS114 cells Lung small cell carcinoma Homo sapiens CVCL_1174
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SBC3 cells Small cell lung cancer Homo sapiens CVCL_1678
HSC-2 cells Oral cavity squamous cell carcinoma Homo sapiens CVCL_1287
HSC-3 cells Oral squamous cell carcinoma Homo sapiens CVCL_1288
HSC-4 cells Cervical lymph node Homo sapiens CVCL_1289
OSC-19 cells Tongue squamous cell carcinoma Homo sapiens CVCL_3086
SCC-25 cells Squamous carcinoma Homo sapiens CVCL_1682
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Response regulation Combined treatment with oxyfedrine (OXY) and sulfasalazine (SSZ) was found to induce accumulation of the cytotoxic aldehyde 4-hydroxynonenal and cell death in SSZ-resistant cancer cells both in vitro and in vivo. And the constitutive activation of Nrf2 results in high expression of xCT and ALDH3A1, and Nrf2 depletion sensitizes Nrf2 overexpressing cancer, such as lung small cell carcinoma, cells to combination therapy with OXY and SSZ.
Experiment 2 Reporting the Ferroptosis Target of This Regulator [2]
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Responsed Drug Dyclonine Approved
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 OSC-19 cells Tongue squamous cell carcinoma Homo sapiens CVCL_3086
HSC-2 cells Oral cavity squamous cell carcinoma Homo sapiens CVCL_1287
HSC-3 cells Oral squamous cell carcinoma Homo sapiens CVCL_1288
HSC-4 cells Cervical lymph node Homo sapiens CVCL_1289
SCC-25 cells Squamous carcinoma Homo sapiens CVCL_1682
DMS114 cells Lung small cell carcinoma Homo sapiens CVCL_1174
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
4T1 cells Mammary carcinoma Mus musculus CVCL_0125
In Vivo Model
HSC-2 or K19-Wnt1/C2mE-KP cells (2 x 106 cells per site) were implanted subcutaneously in the flank of athymic nude mice (CLEA Japan) or C57BL6 mice (CLEA Japan), respectively. The mice were then injected intraperitoneally with physiological saline or sulfasalazine (350 mg/kg per day), or with combinations of physiological saline, sulfasalazine (400 mg/kg per day), and dyclonine hydrochloride (5 mg/kg per day).

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Response regulation Sulfasalazine-resistant head and neck squamous cell carcinoma (HNSCC) cells were found to highly express ALDH3A1 and knockdown of ALDH3A1 rendered these cells sensitive to sulfasalazine. The combination of dyclonine and sulfasalazine cooperatively suppressed the growth of highly ALDH3A1-expressing HNSCC or gastric tumors that were resistant to sulfasalazine monotherapy.
Lung cancer [ICD-11: 2C25]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [1]
Target Regulator Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) Protein coding
 Regulator Info 
Responsed Drug Oxyfedrine Investigative
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 DMS114 cells Lung small cell carcinoma Homo sapiens CVCL_1174
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SBC3 cells Small cell lung cancer Homo sapiens CVCL_1678
HSC-2 cells Oral cavity squamous cell carcinoma Homo sapiens CVCL_1287
HSC-3 cells Oral squamous cell carcinoma Homo sapiens CVCL_1288
HSC-4 cells Cervical lymph node Homo sapiens CVCL_1289
OSC-19 cells Tongue squamous cell carcinoma Homo sapiens CVCL_3086
SCC-25 cells Squamous carcinoma Homo sapiens CVCL_1682
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Response regulation Combined treatment with oxyfedrine (OXY) and sulfasalazine (SSZ) was found to induce accumulation of the cytotoxic aldehyde 4-hydroxynonenal and cell death in SSZ-resistant cancer cells both in vitro and in vivo. And the constitutive activation of Nrf2 results in high expression of xCT and ALDH3A1, and Nrf2 depletion sensitizes Nrf2 overexpressing cancer, such as lung small cell carcinoma, cells to combination therapy with OXY and SSZ.
Head neck squamous cell carcinoma [ICD-11: 2D60]
 Disease Info 
In total 1 item(s) under this disease
Experiment 1 Reporting the Ferroptosis-centered Disease Response [2]
Target Regulator Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1) Protein coding
 Regulator Info 
Responsed Drug Dyclonine Approved
 Drug Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 OSC-19 cells Tongue squamous cell carcinoma Homo sapiens CVCL_3086
HSC-2 cells Oral cavity squamous cell carcinoma Homo sapiens CVCL_1287
HSC-3 cells Oral squamous cell carcinoma Homo sapiens CVCL_1288
HSC-4 cells Cervical lymph node Homo sapiens CVCL_1289
SCC-25 cells Squamous carcinoma Homo sapiens CVCL_1682
DMS114 cells Lung small cell carcinoma Homo sapiens CVCL_1174
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
4T1 cells Mammary carcinoma Mus musculus CVCL_0125
In Vivo Model
HSC-2 or K19-Wnt1/C2mE-KP cells (2 x 106 cells per site) were implanted subcutaneously in the flank of athymic nude mice (CLEA Japan) or C57BL6 mice (CLEA Japan), respectively. The mice were then injected intraperitoneally with physiological saline or sulfasalazine (350 mg/kg per day), or with combinations of physiological saline, sulfasalazine (400 mg/kg per day), and dyclonine hydrochloride (5 mg/kg per day).

    Click to Show/Hide
Response regulation Sulfasalazine-resistant head and neck squamous cell carcinoma (HNSCC) cells were found to highly express ALDH3A1 and knockdown of ALDH3A1 rendered these cells sensitive to sulfasalazine. The combination of dyclonine and sulfasalazine cooperatively suppressed the growth of highly ALDH3A1-expressing HNSCC or gastric tumors that were resistant to sulfasalazine monotherapy.
Dyclonine [Approved]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [2]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Head neck squamous cell carcinoma ICD-11: 2D60
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
In Vitro Model
 OSC-19 cells Tongue squamous cell carcinoma Homo sapiens CVCL_3086
HSC-2 cells Oral cavity squamous cell carcinoma Homo sapiens CVCL_1287
HSC-3 cells Oral squamous cell carcinoma Homo sapiens CVCL_1288
HSC-4 cells Cervical lymph node Homo sapiens CVCL_1289
SCC-25 cells Squamous carcinoma Homo sapiens CVCL_1682
DMS114 cells Lung small cell carcinoma Homo sapiens CVCL_1174
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
4T1 cells Mammary carcinoma Mus musculus CVCL_0125
In Vivo Model
HSC-2 or K19-Wnt1/C2mE-KP cells (2 x 106 cells per site) were implanted subcutaneously in the flank of athymic nude mice (CLEA Japan) or C57BL6 mice (CLEA Japan), respectively. The mice were then injected intraperitoneally with physiological saline or sulfasalazine (350 mg/kg per day), or with combinations of physiological saline, sulfasalazine (400 mg/kg per day), and dyclonine hydrochloride (5 mg/kg per day).

    Click to Show/Hide
Response regulation Sulfasalazine-resistant head and neck squamous cell carcinoma (HNSCC) cells were found to highly express ALDH3A1 and knockdown of ALDH3A1 rendered these cells sensitive to sulfasalazine. The combination of dyclonine and sulfasalazine cooperatively suppressed the growth of highly ALDH3A1-expressing HNSCC or gastric tumors that were resistant to sulfasalazine monotherapy.
Oxyfedrine [Investigative]
 Drug Info 
In total 1 item(s) under this drug
Experiment 1 Reporting the Ferroptosis-centered Drug Response [1]
Drug for Ferroptosis Inducer
Response Target Unspecific Target
Responsed Disease Lung cancer ICD-11: 2C25
 Disease Info 
Pathway Response Fatty acid metabolism hsa01212
Ferroptosis hsa04216
Cell Process Cell ferroptosis
Cell proliferation
In Vitro Model
 DMS114 cells Lung small cell carcinoma Homo sapiens CVCL_1174
HCT 116 cells Colon carcinoma Homo sapiens CVCL_0291
SBC3 cells Small cell lung cancer Homo sapiens CVCL_1678
HSC-2 cells Oral cavity squamous cell carcinoma Homo sapiens CVCL_1287
HSC-3 cells Oral squamous cell carcinoma Homo sapiens CVCL_1288
HSC-4 cells Cervical lymph node Homo sapiens CVCL_1289
OSC-19 cells Tongue squamous cell carcinoma Homo sapiens CVCL_3086
SCC-25 cells Squamous carcinoma Homo sapiens CVCL_1682
A-549 cells Lung adenocarcinoma Homo sapiens CVCL_0023
Response regulation Combined treatment with oxyfedrine (OXY) and sulfasalazine (SSZ) was found to induce accumulation of the cytotoxic aldehyde 4-hydroxynonenal and cell death in SSZ-resistant cancer cells both in vitro and in vivo. And the constitutive activation of Nrf2 results in high expression of xCT and ALDH3A1, and Nrf2 depletion sensitizes Nrf2 overexpressing cancer, such as lung small cell carcinoma, cells to combination therapy with OXY and SSZ.
References
Ref 1 Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy. Cancer Sci. 2020 Jan;111(1):127-136. doi: 10.1111/cas.14224. Epub 2019 Nov 22.
Ref 2 Synthetic lethality of the ALDH3A1 inhibitor dyclonine and xCT inhibitors in glutathione deficiency-resistant cancer cells. Oncotarget. 2018 Sep 18;9(73):33832-33843. doi: 10.18632/oncotarget.26112. eCollection 2018 Sep 18.