InterPAD - DETAILS

MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQE
QLQKEQEKAFFAQLQLDEETGEFLPIQPAQHIQSETSGSANYSQVAHIPKSDALYFDDCM
QLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGM
QQDIEQVWEELLSIPELQCLNIENDKLVETTMVPSPEAKLTEVDNYHFYSSIPSMEKEVG
NCSPHFLNAFEDSFSSILSTEDPNQLTVNSLNSDATVNTDFGDEFYSAFIAEPSISNSMP
SPATLSHSLSELLNGPIDVSDLSLCKAFNQNHPESTAEFNDSDSGISLNTSPSVASPEHS
VESSSYGDTLLGLSDSEVEELDSAPGSVKQNGPKTPVHSSGDMVQPLSPSQGQSTHVHDA
QCENTPEKELPVSPGHRKTPFTKDKHSSRLEAHLTRDELRAKALHIPFPVEKIINLPVVD
FNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRKRKLENIVELEQDLDHLKDEKEKLL
KEKGENDKSLHLLKKQLSTLYLEVFSMLRDEDGKPYSPSEYSLQQTRDGNVFLVPKSKKP
DVKKN

No.	Title	Href
1	Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage. Sci Rep. 2022 Apr 20;12(1):6494. doi: 10.1038/s41598-022-10517-0.	`Click`
2	Probable Mechanisms of Doxorubicin Antitumor Activity Enhancement by Ginsenoside Rh2. Molecules. 2022 Jan 19;27(3):628. doi: 10.3390/molecules27030628.	`Click`
3	Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity With Cisplatin. Front Pharmacol. 2018 Jun 18;9:638. doi: 10.3389/fphar.2018.00638.	`Click`
4	Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells. Nutr Res. 2015 Jul;35(7):610-7. doi: 10.1016/j.nutres.2015.05.011.	`Click`
5	All-trans retinoic acid enhances the cytotoxic effect of decitabine on myelodysplastic syndromes and acute myeloid leukaemia by activating the RARα-Nrf2 complex. Br J Cancer. 2023 Feb;128(4):691-701. doi: 10.1038/s41416-022-02074-0.	`Click`
6	Baicalein enhanced cisplatin sensitivity of gastric cancer cells by inducing cell apoptosis and autophagy via Akt/mTOR and Nrf2/Keap 1 pathway. Biochem Biophys Res Commun. 2020 Oct 20;531(3):320-327. doi: 10.1016/j.bbrc.2020.07.045.	`Click`
7	Brucein D augments the chemosensitivity of gemcitabine in pancreatic cancer via inhibiting the Nrf2 pathway. J Exp Clin Cancer Res. 2022 Mar 10;41(1):90. doi: 10.1186/s13046-022-02270-z.	`Click`
8	Inhibition of Nrf2-mediated glucose metabolism by brusatol synergistically sensitizes acute myeloid leukemia to Ara-C. Biomed Pharmacother. 2021 Oct;142:111652. doi: 10.1016/j.biopha.2021.111652.	`Click`
9	Camptothecin Sensitizes Hepatocellular Carcinoma Cells to Sorafenib- Induced Ferroptosis Via Suppression of Nrf2. Inflammation. 2023 Aug;46(4):1493-1511. doi: 10.1007/s10753-023-01823-4.	`Click`
10	Dehydrobruceine B enhances the cisplatin-induced cytotoxicity through regulation of the mitochondrial apoptotic pathway in lung cancer A549 cells. Biomed Pharmacother. 2017 May;89:623-631. doi: 10.1016/j.biopha.2017.02.055.	`Click`
11	Indole-3-Carbinol (I3C) enhances the sensitivity of murine breast adenocarcinoma cells to doxorubicin (DOX) through inhibition of NF-κβ, blocking angiogenesis and regulation of mitochondrial apoptotic pathway. Chem Biol Interact. 2018 Jun 25;290:19-36. doi: 10.1016/j.cbi.2018.05.005.	`Click`
12	Hederagenin Induces Apoptosis in Cisplatin-Resistant Head and Neck Cancer Cells by Inhibiting the Nrf2-ARE Antioxidant Pathway. Oxid Med Cell Longev. 2017;2017:5498908. doi:10.1155/2017/5498908	`Click`
13	A novel combination therapy with Cabozantinib and Honokiol effectively inhibits c-Met-Nrf2-induced renal tumor growth through increased oxidative stress. Redox Biol. 2023 Dec;68:102945. doi: 10.1016/j.redox.2023.102945.	`Click`
14	Luteolin Shifts Oxaliplatin-Induced Cell Cycle Arrest at G₀/G₁ to Apoptosis in HCT116 Human Colorectal Carcinoma Cells. Nutrients. 2019 Apr 2;11(4):770. doi: 10.3390/nu11040770.	`Click`
15	Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway. Molecules. 2021 Oct 26;26(21):6452. doi: 10.3390/molecules26216452.	`Click`
16	Lycopene sensitizes the cervical cancer cells to cisplatin via targeting nuclear factor- kappa B (NF-κB) pathway. Turk J Med Sci. 2021 Feb 26;51(1):368-374. doi: 10.3906/sag-2005-413.	`Click`
17	Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells. Biomed Pharmacother. 2023 Jan;157:114039. doi: 10.1016/j.biopha.2022.114039.	`Click`
18	Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway. Int J Mol Sci. 2023 May 5;24(9):8265. doi: 10.3390/ijms24098265.	`Click`
19	Tiliroside targets TBK1 to induce ferroptosis and sensitize hepatocellular carcinoma to sorafenib. Phytomedicine. 2023 Mar;111:154668. doi: 10.1016/j.phymed.2023.154668.	`Click`
20	Trigonelline inhibits Nrf2 via EGFR signalling pathway and augments efficacy of Cisplatin and Etoposide in NSCLC cells. Toxicol In Vitro. 2021 Feb;70:105038. doi: 10.1016/j.tiv.2020.105038.	`Click`
21	Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin. Mol Med Rep. 2023 Jan;27(1):17. doi: 10.3892/mmr.2022.12904.	`Click`
22	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`
23	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`
24	Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer. Apoptosis. 2016;21(11):1265-1278. doi:10.1007/s10495-016-1284-8	`Click`
25	Ligustrazine-Derived Chalcones-Modified Platinum(IV) Complexes Intervene in Cisplatin Resistance in Pancreatic Cancer through Ferroptosis and Apoptosis. J Med Chem. 2023 Oct 12;66(19):13587-13606. doi: 10.1021/acs.jmedchem.3c00922.	`Click`
26	Berberine reverses Lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS. Cancer Biol Ther. 2016;17(9):925-934. doi:10.1080/15384047.2016.1210728	`Click`
27	Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling PathwayBrusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway. Oxid Med Cell Longev. 2018 Apr 18;2018:2360427. doi: 10.1155/2018/2360427.	`Click`
28	Parthenolide prevents resistance of MDA-MB231 cells to doxorubicin and mitoxantrone: the role of Nrf2. Cell Death Discov. 2017;3:17078. Published 2017 Dec 4. doi:10.1038/cddiscovery.2017.78	`Click`
29	Quercetin reverses 5-fluorouracil resistance in colon cancer cells by modulating the NRF2/HO-1 pathway. Eur J Histochem. 2023 Aug 7;67(3):3719. doi: 10.4081/ejh.2023.3719.	`Click`
30	Ursolic acid sensitizes cisplatin-resistant HepG2/DDP cells to cisplatin via inhibiting Nrf2/ARE pathway. Drug Des Devel Ther. 2016 Oct 25;10:3471-3481. doi: 10.2147/DDDT.S110505.	`Click`
31	Drug resistance associates with activation of Nrf2 in MCF-7/DOX cells, and wogonin reverses it by down-regulating Nrf2-mediated cellular defense response. Mol Carcinog. 2013;52(10):824-834. doi:10.1002/mc.21921	`Click`

No.

Title

Href

Amygdalin potentiates the anti-cancer effect of Sorafenib on Ehrlich ascites carcinoma and ameliorates the associated liver damage. Sci Rep. 2022 Apr 20;12(1):6494. doi: 10.1038/s41598-022-10517-0.

Click

Probable Mechanisms of Doxorubicin Antitumor Activity Enhancement by Ginsenoside Rh2. Molecules. 2022 Jan 19;27(3):628. doi: 10.3390/molecules27030628.

Click

Mangiferin Ameliorates Cisplatin Induced Acute Kidney Injury by Upregulating Nrf-2 via the Activation of PI3K and Exhibits Synergistic Anticancer Activity With Cisplatin. Front Pharmacol. 2018 Jun 18;9:638. doi: 10.3389/fphar.2018.00638.

Click

Synergy between sulforaphane and selenium in protection against oxidative damage in colonic CCD841 cells. Nutr Res. 2015 Jul;35(7):610-7. doi: 10.1016/j.nutres.2015.05.011.

Click

All-trans retinoic acid enhances the cytotoxic effect of decitabine on myelodysplastic syndromes and acute myeloid leukaemia by activating the RARα-Nrf2 complex. Br J Cancer. 2023 Feb;128(4):691-701. doi: 10.1038/s41416-022-02074-0.

Click

Baicalein enhanced cisplatin sensitivity of gastric cancer cells by inducing cell apoptosis and autophagy via Akt/mTOR and Nrf2/Keap 1 pathway. Biochem Biophys Res Commun. 2020 Oct 20;531(3):320-327. doi: 10.1016/j.bbrc.2020.07.045.

Click

Brucein D augments the chemosensitivity of gemcitabine in pancreatic cancer via inhibiting the Nrf2 pathway. J Exp Clin Cancer Res. 2022 Mar 10;41(1):90. doi: 10.1186/s13046-022-02270-z.

Click

Inhibition of Nrf2-mediated glucose metabolism by brusatol synergistically sensitizes acute myeloid leukemia to Ara-C. Biomed Pharmacother. 2021 Oct;142:111652. doi: 10.1016/j.biopha.2021.111652.

Click

Camptothecin Sensitizes Hepatocellular Carcinoma Cells to Sorafenib- Induced Ferroptosis Via Suppression of Nrf2. Inflammation. 2023 Aug;46(4):1493-1511. doi: 10.1007/s10753-023-01823-4.

Click

Dehydrobruceine B enhances the cisplatin-induced cytotoxicity through regulation of the mitochondrial apoptotic pathway in lung cancer A549 cells. Biomed Pharmacother. 2017 May;89:623-631. doi: 10.1016/j.biopha.2017.02.055.

Click

Indole-3-Carbinol (I3C) enhances the sensitivity of murine breast adenocarcinoma cells to doxorubicin (DOX) through inhibition of NF-κβ, blocking angiogenesis and regulation of mitochondrial apoptotic pathway. Chem Biol Interact. 2018 Jun 25;290:19-36. doi: 10.1016/j.cbi.2018.05.005.

Click

Hederagenin Induces Apoptosis in Cisplatin-Resistant Head and Neck Cancer Cells by Inhibiting the Nrf2-ARE Antioxidant Pathway. Oxid Med Cell Longev. 2017;2017:5498908. doi:10.1155/2017/5498908

Click

A novel combination therapy with Cabozantinib and Honokiol effectively inhibits c-Met-Nrf2-induced renal tumor growth through increased oxidative stress. Redox Biol. 2023 Dec;68:102945. doi: 10.1016/j.redox.2023.102945.

Click

Luteolin Shifts Oxaliplatin-Induced Cell Cycle Arrest at G₀/G₁ to Apoptosis in HCT116 Human Colorectal Carcinoma Cells. Nutrients. 2019 Apr 2;11(4):770. doi: 10.3390/nu11040770.

Click

Luteolin Inhibits Breast Cancer Stemness and Enhances Chemosensitivity through the Nrf2-Mediated Pathway. Molecules. 2021 Oct 26;26(21):6452. doi: 10.3390/molecules26216452.

Click

Lycopene sensitizes the cervical cancer cells to cisplatin via targeting nuclear factor- kappa B (NF-κB) pathway. Turk J Med Sci. 2021 Feb 26;51(1):368-374. doi: 10.3906/sag-2005-413.

Click

Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells. Biomed Pharmacother. 2023 Jan;157:114039. doi: 10.1016/j.biopha.2022.114039.

Click

Natural Compounds, Optimal Combination of Brusatol and Polydatin Promote Anti-Tumor Effect in Breast Cancer by Targeting Nrf2 Signaling Pathway. Int J Mol Sci. 2023 May 5;24(9):8265. doi: 10.3390/ijms24098265.

Click

Tiliroside targets TBK1 to induce ferroptosis and sensitize hepatocellular carcinoma to sorafenib. Phytomedicine. 2023 Mar;111:154668. doi: 10.1016/j.phymed.2023.154668.

Click

Trigonelline inhibits Nrf2 via EGFR signalling pathway and augments efficacy of Cisplatin and Etoposide in NSCLC cells. Toxicol In Vitro. 2021 Feb;70:105038. doi: 10.1016/j.tiv.2020.105038.

Click

Triptolide promotes ferroptosis by suppressing Nrf2 to overcome leukemia cell resistance to doxorubicin. Mol Med Rep. 2023 Jan;27(1):17. doi: 10.3892/mmr.2022.12904.

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

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

Targeting Nrf2 with wogonin overcomes cisplatin resistance in head and neck cancer. Apoptosis. 2016;21(11):1265-1278. doi:10.1007/s10495-016-1284-8

Click

Ligustrazine-Derived Chalcones-Modified Platinum(IV) Complexes Intervene in Cisplatin Resistance in Pancreatic Cancer through Ferroptosis and Apoptosis. J Med Chem. 2023 Oct 12;66(19):13587-13606. doi: 10.1021/acs.jmedchem.3c00922.

Click

Berberine reverses Lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS. Cancer Biol Ther. 2016;17(9):925-934. doi:10.1080/15384047.2016.1210728

Click

Brusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling PathwayBrusatol Enhances the Chemotherapy Efficacy of Gemcitabine in Pancreatic Cancer via the Nrf2 Signalling Pathway. Oxid Med Cell Longev. 2018 Apr 18;2018:2360427. doi: 10.1155/2018/2360427.

Click

Parthenolide prevents resistance of MDA-MB231 cells to doxorubicin and mitoxantrone: the role of Nrf2. Cell Death Discov. 2017;3:17078. Published 2017 Dec 4. doi:10.1038/cddiscovery.2017.78

Click

Quercetin reverses 5-fluorouracil resistance in colon cancer cells by modulating the NRF2/HO-1 pathway. Eur J Histochem. 2023 Aug 7;67(3):3719. doi: 10.4081/ejh.2023.3719.

Click

Ursolic acid sensitizes cisplatin-resistant HepG2/DDP cells to cisplatin via inhibiting Nrf2/ARE pathway. Drug Des Devel Ther. 2016 Oct 25;10:3471-3481. doi: 10.2147/DDDT.S110505.

Click

Drug resistance associates with activation of Nrf2 in MCF-7/DOX cells, and wogonin reverses it by down-regulating Nrf2-mediated cellular defense response. Mol Carcinog. 2013;52(10):824-834. doi:10.1002/mc.21921

Click

Name	Nuclear factor erythroid 2-related factor 2
UniProt ID	NF2L2_HUMAN
Gene Name	NFE2L2
Gene ID	4780
Synonyms	NFE2L2, HEBP1, IMDDHH, NRF2, Nrf-2
Sequence	MMDLELPPPGLPSQQDMDLIDILWRQDIDLGVSREVFDFSQRRKEYELEKQKKLEKERQE QLQKEQEKAFFAQLQLDEETGEFLPIQPAQHIQSETSGSANYSQVAHIPKSDALYFDDCM QLLAQTFPFVDDNEVSSATFQSLVPDIPGHIESPVFIATNQAQSPETSVAQVAPVDLDGM QQDIEQVWEELLSIPELQCLNIENDKLVETTMVPSPEAKLTEVDNYHFYSSIPSMEKEVG NCSPHFLNAFEDSFSSILSTEDPNQLTVNSLNSDATVNTDFGDEFYSAFIAEPSISNSMP SPATLSHSLSELLNGPIDVSDLSLCKAFNQNHPESTAEFNDSDSGISLNTSPSVASPEHS VESSSYGDTLLGLSDSEVEELDSAPGSVKQNGPKTPVHSSGDMVQPLSPSQGQSTHVHDA QCENTPEKELPVSPGHRKTPFTKDKHSSRLEAHLTRDELRAKALHIPFPVEKIINLPVVD FNEMMSKEQFNEAQLALIRDIRRRGKNKVAAQNCRKRKLENIVELEQDLDHLKDEKEKLL KEKGENDKSLHLLKKQLSTLYLEVFSMLRDEDGKPYSPSEYSLQQTRDGNVFLVPKSKKP DVKKN
Pathway Map	`MAP LINK`
KEGG ID	hsa4780
TTD ID	T88505
Pfam	PF00170; PF03131; PF07716; PF15996; PF17001

Pair Name	Amygdalin, Sorafenib
Phytochemical Name	Amygdalin
Anticancer drug Name	Sorafenib
Disease Info	[ICD-11: 2D91]	Ehrlich ascites carcinoma	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice.

Pair Name	Ginsenoside Rh2, Doxorubicin
Phytochemical Name	Ginsenoside Rh2
Anticancer drug Name	Doxorubicin
Disease Info	[ICD-11:2D40]	Ehrlich's adenocarcinoma	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Rh2-induced direct activation of Nrf2 might provide additional benefits by minimizing DOX toxicity towards non-cancerous cells.

Pair Name	Mangiferin, Cisplatin
Phytochemical Name	Mangiferin
Anticancer drug Name	Cisplatin
Disease Info	Nephrotoxicity		Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	The study reveals a mechanistic basis of mangiferin action against cisplatin induced nephrotoxicity. Since Mangiferin shows synergistic anticancer activity with cisplatin, it can be considered as a promising drug candidate, to be used in combination with cisplatin.

Pair Name	Sulforaphane, Selenium
Phytochemical Name	Sulforaphane
Anticancer drug Name	Selenium
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Combined SFN and Se treatment synergistically upregulated TrxR-1, which plays a significant role in maintaining intracellular redox homeostasis and contributed to the SFN-induced protection against free radical-mediated oxidative damage in normal colonic cells.

Pair Name	All-trans retinoic acid, Decitabine
Phytochemical	All-trans-retinoic acid
Drug	Decitabine
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	These results demonstrate that combining DAC and ATRA has potential for the clinical treatment of HR-MDS/AML and merits further exploration.

Pair Name	Baicalein, Cisplatin
Phytochemical	Baicalein
Drug	Cisplatin
Disease Info	[ICD-11: 2B72]	Gastric cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Activity
Result	Baicalein enhanced cisplatin sensitivity of gastric cancer cells by inducing cell apoptosis and autophagy via Akt/mTOR and Nrf2/Keap 1 pathway

Pair Name	Bruceine D, Gemcitabine
Phytochemical	Bruceine D
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10.0]	Pancreatic ductal adenocarcinoma	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Our experimental findings indicate that BD, a potent Nrf2 inhibitor, holds promise for further development into a novel adjuvant therapy for PDAC.

Pair Name	Brusatol, Cytarabine
Phytochemical	Brusatol
Drug	Cytarabine
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Inhibition of Nrf2-mediated glucose metabolism by brusatol synergistically sensitizes acute myeloid leukemia to Ara-C

Pair Name	Camptothecin, Sorafenib
Phytochemical	Camptothecin
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	The synergetic combination significantly increases lipid peroxidation and iron concentration, decreases TAC, GPX4 and GR activity, and reduces the expression of both Nrf2 and SLC7A11. The downregulation of Nrf2 expression has a vital role in the reduction of resistance mediators to sorafenib against HCC cells like (p62, MT1G, and ABCG2) and improves the cellular uptake of sorafenib. The current study provided evidence that Nrf2 inhibition by CPT improves sorafenib's sensitivity and reduces sorafenib's resistance via the augmentation of sorafenib's ferroptosis action.

Pair Name	Dehydrobruceine B, Cisplatin
Phytochemical	Dehydrobruceine B
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	These results generated a rationale for further investigation of DHB combined with CDDP as a potential therapeutic strategy in lung cancer.

Pair Name	Glucosinalbate, Doxorubicin
Phytochemical	Glucosinalbate
Drug	Doxorubicin
Disease Info	[ICD-11: 2C90]	Ehrlich ascites carcinoma	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	The present study clearly suggested therapeutic benefit of I3C in combination with DOX by augmenting anticancer efficacy and diminishing toxicity to the host.

Pair Name	Hederagenin, Cisplatin
Phytochemical	Hederagenin
Drug	Cisplatin
Disease Info	Head and neck cancer
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Hederagenin effectively targets cisplatin-resistant HNC cells in vitro and in vivo. Consistent with its effects in other types of cancer, hederagenin markedly induces apoptosis in HNC cells by activating the mitochondria-driven intrinsic apoptotic pathway. We demonstrated that the apoptosis-inducing effects of hederagenin are mediated by the inhibition of the Nrf2-ARE antioxidant pathway.

Pair Name	Honokiol, Cabozantinib
Phytochemical	Honokiol
Drug	Cabozantinib
Disease Info	[ICD-11: 2C90.0]	Renal cell carcinoma	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Cabozantinib + Honokiol combination can significantly inhibit c-Met-induced and Nrf2-mediated anti-oxidant pathway in renal cancer cells to promote increased oxidative stress and tumor cell death.

Pair Name	Luteolin, Oxaliplatin
Phytochemical	Luteolin
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Activity
Result	Luteolin can induce p53-mediated apoptosis regardless of oxaliplatin treatment and may eliminate oxaliplatin-resistant p53-null colorectal cells

Pair Name	Luteolin, Paclitaxel
Phytochemical	Luteolin
Drug	Paclitaxel
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	These findings suggest that luteolin treatment significantly attenuated the hallmarks of breast cancer stemness by downregulating Nrf2-mediated expressions. Luteolin constitutes a potential agent for use in cancer stemness-targeted breast cancer treatments.

Pair Name	Lycopene, Cisplatin
Phytochemical	Lycopene
Drug	Cisplatin
Disease Info	[ICD-11: 2C77]	Cervical cancer	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Lycopene increases the sensitization of cervical cancer cells to cisplatin via inhibition of cell viability, up-regulation of Bax expression, and down-regulation of Bcl-2 expression. Furthermore, the anticancer effect of lycopene might be also associated with suppression of NF-κB-mediated inflammatory responses, and modulation of Nrf2-mediated oxidative stress. The results of the present study suggest that lycopene and concurrent cisplatin chemotherapy might have a role in improving the treatment of cervical cancer.

Pair Name	Periplocin, Gemcitabine
Phytochemical	Periplocin
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Periplocin exerts antitumor activity by regulating Nrf2-mediated signaling pathway in gemcitabine-resistant pancreatic cancer cells

Pair Name	Polydatin, Brusatol
Phytochemical	Polydatin
Drug	Brusatol
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	We could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment.

Pair Name	Tiliroside, Sorafenib
Phytochemical	Tiliroside
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Our findings imply that tiliroside is a potent TBK1 inhibitor and a candidate natural anti-cancer product that could function as a sensitizer of sorafenib in HCC treatment by targeting TBK1 to induce ferroptosis.

Pair Name	Trigonelline, Cisplatin
Phytochemical	Trigonelline
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Phosphorylation
Result	Our study demonstrated that Trigonelline blocks Nrf2 activation and its nuclear translocation via inhibition of EGFR signalling pathway. It has improved responsiveness of NSCLC cells for Cisplatin and Etoposide and could be a promising choice for lung cancer therapy. Toxicol In Vitro. 2021 Feb;70:105038. doi: 10.1016/j.tiv.2020.105038.

Pair Name	Triptolide, Doxorubicin
Phytochemical	Triptolide
Drug	Doxorubicin
Disease Info	[ICD-11: 2B33.4]	Leukemia	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	The present study indicated that Nrf2 served a critical role in leukemia cell resistance to DOX and triptolide‑induced ferroptosis and suggested a potential strategy of combination therapy using triptolide and DOX in leukemia treatment.

Pair Name	Vitamin C, Erastin
Phytochemical	Vitamin C
Drug	Erastin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Up-regulation	Nuclear factor erythroid 2-related factor 2	Expression
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	Wogonin, Cisplatin
Phytochemical	Wogonin
Drug	Cisplatin
Disease Info	Head and neck cancer
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Wogonin induced selective cell death by targeting the antioxidant defense mechanisms enhanced in the resistant HNC cells and activating cell death pathways involving PUMA and PARP. Hence, wogonin significantly sensitized resistant HNC cells to cisplatin both in vitro and in vivo. Wogonin is a promising anticancer candidate that induces ROS accumulation and selective cytotoxicity in HNC cells and can help to overcome cisplatin-resistance in this cancer.

Pair Name	2,3,5,6-Tetramethylpyrazine, Cisplatin
Phytochemical	2,3,5,6-Tetramethylpyrazine
Drug	Cisplatin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	A series of ligustrazine-derived chalcones-modified platinum(IV) complexes were synthesized and evaluated for their anti-proliferative potency and generated an optimal platinum(IV) complex 16a. The above-described results indicated that 16a obtained different anti-cancer mechanisms of CDDP, which could initiate mitochondria-dependent apoptosis and xCT-GPX4 axial-mediated ferroptosis in PANC-1/CDDP cells.

Pair Name	Berberine, Lapatinib
Phytochemical	Berberine
Drug	Lapatinib
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Berberine reverses Lapatinib resistance of HER2-positive breast cancer cells by increasing the level of ROS

Pair Name	Brusatol, Gemcitabine
Phytochemical	Brusatol
Drug	Gemcitabine
Disease Info	[ICD-11: 2C10]	Pancreatic cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Our results suggest that brusatol is capable of enhancing the antitumour effects of gemcitabine in both pancreatic cancer cells and PANC-1 xenografts via suppressing the Nrf2 pathway.

Pair Name	Parthenolide, Doxorubicin
Phytochemical	Parthenolide
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	PN prevented the acquisition of resistance induced by Mitox and DOX treatment in MDA-MB231 cells. This effect was mediated by inhibition of overexpression of both Nrf2 and its target activities. Therefore, within MDA-MB231 cell lines, PN not only exerts toxic effects on stem-like cells, which are responsible for tumour recurrence, but also prevents drug resistance

Pair Name	Quercetin, Fluorouracil
Phytochemical	Quercetin
Drug	Fluorouracil
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Our results suggest that Que reverses 5-FU resistance in CC cells via modulating the Nrf2/HO-1 pathway.

Pair Name	Ursolic acid, Cisplatin
Phytochemical	Ursolic acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	The results confirmed the sensibilization of UA on HepG2/DDP cells to cisplatin, which was possibly mediated via the Nrf2/antioxidant response element pathway.

Pair Name	Wogonin, Doxorubicin
Phytochemical	Wogonin
Drug	Doxorubicin
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Nuclear factor erythroid 2-related factor 2	Expression
Result	Wogonin reversed drug resistance and its reversal mechanism might be due to the suppression of Nrf2 signaling pathway, indicating the feasibility of using Nrf2 inhibitors to increase efficacy of chemotherapeutic drugs.