InterPAD - DETAILS

MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAY
DHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYI
VQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL
KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLS
NRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSD
SKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERL
KELIFQETARFQPGVLEAP

No.	Title	Href
1	Amentoflavone Enhances the Therapeutic Efficacy of Sorafenib by Inhibiting Anti-apoptotic Potential and Potentiating Apoptosis in Hepatocellular Carcinoma In Vivo. Anticancer Res. 2018 Apr;38(4):2119-2125. doi: 10.21873/anticanres.12452.	`Click`
2	Suppression of AKT Potentiates Synergistic Cytotoxicity of Apigenin with TRAIL in Anaplastic Thyroid Carcinoma Cells. Anticancer Res. 2015 Dec;35(12):6529-37.	`Click`
3	Apigenin potentiates TRAIL therapy of non-small cell lung cancer via upregulating DR4/DR5 expression in a p53-dependent manner. Sci Rep. 2016 Oct 18;6:35468. doi: 10.1038/srep35468.	`Click`
4	Artesunate exhibits synergistic anti-cancer effects with cisplatin on lung cancer A549 cells by inhibiting MAPK pathway. Gene. 2021 Jan 15;766:145134. doi: 10.1016/j.gene.2020.145134.	`Click`
5	β-elemene enhances both radiosensitivity and chemosensitivity of glioblastoma cells through the inhibition of the ATM signaling pathway. Oncol Rep. 2015 Aug;34(2):943-51. doi: 10.3892/or.2015.4050.	`Click`
6	Combination of Biochanin A and Temozolomide Impairs Tumor Growth by Modulating Cell Metabolism in Glioblastoma Multiforme. Anticancer Res. 2019 Jan;39(1):57-66. doi: 10.21873/anticanres.13079.	`Click`
7	Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 2012 Aug;138(8):1279-89. doi: 10.1007/s00432-012-1204-4.	`Click`
8	Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro. Cell Physiol Biochem. 2018;48(4):1433-1442. doi: 10.1159/000492253.	`Click`
9	Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells. Int J Mol Sci. 2021 Aug 10;22(16):8586. doi: 10.3390/ijms22168586.	`Click`
10	Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases. Anticancer Drugs. 2015 Jun;26(5):540-6. doi: 10.1097/CAD.0000000000000218.	`Click`
11	Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53. Chem Biol Interact. 2015 May 5;232:12-20. doi: 10.1016/j.cbi.2015.03.003.	`Click`
12	Doxorubicin has a synergistic cytotoxicity with cucurbitacin B in anaplastic thyroid carcinoma cells. Tumour Biol. 2017 Feb;39(2):1010428317692252. doi: 10.1177/1010428317692252.	`Click`
13	Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin. Exp Biol Med (Maywood). 2015 Nov;240(11):1416-25. doi: 10.1177/1535370215571881.	`Click`
14	The role of daurisoline treatment in hepatocellular carcinoma: Inhibiting vasculogenic mimicry formation and enhancing sensitivity to sorafenib. Phytomedicine. 2021 Nov;92:153740. doi: 10.1016/j.phymed.2021.153740.	`Click`
15	XIAP inhibition and generation of reactive oxygen species enhances TRAIL sensitivity in inflammatory breast cancer cells. Mol Cancer Ther. 2012;11(7):1518-1527. doi:10.1158/1535-7163.MCT-11-0787	`Click`
16	Emodin and Its Combination with Cytarabine Induce Apoptosis in Resistant Acute Myeloid Leukemia Cells in Vitro and in Vivo. Cell Physiol Biochem. 2018;48(5):2061-2073. doi: 10.1159/000492544.	`Click`
17	Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget. 2015 Sep 29;6(29):28296-311. doi: 10.18632/oncotarget.5064.	`Click`
18	Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling. Br J Cancer. 2014 Jan 21;110(2):341-52. doi: 10.1038/bjc.2013.752.	`Click`
19	Downregulation of BCL2 by AT-101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner. Br J Haematol. 2012 Apr;157(1):59-66. doi: 10.1111/j.1365-2141.2011.08984.x.	`Click`
20	Honokiol augments the anti-cancer effects of oxaliplatin in colon cancer cells. Acta Biochim Biophys Sin (Shanghai). 2013 Sep;45(9):773-9. doi: 10.1093/abbs/gmt071.	`Click`
21	Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells. Chem Biol Interact. 2022 Sep 25;365:110076. doi: 10.1016/j.cbi.2022.110076.	`Click`
22	Sulforaphene-Carboplatin Combination Synergistically Enhances Apoptosis by Disruption of Mitochondrial Membrane Potential and Cell Cycle Arrest in Human Non-Small Cell Lung Carcinoma. J Med Food. 2016 Sep;19(9):860-9. doi: 10.1089/jmf.2016.3675.	`Click`
23	Sulforaphene Enhances The Efficacy of Photodynamic Therapy In Anaplastic Thyroid Cancer Through Ras/RAF/MEK/ERK Pathway Suppression. J Photochem Photobiol B. 2018 Feb;179:46-53. doi: 10.1016/j.jphotobiol.2017.12.013.	`Click`
24	Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid. J Pharm Pharmacol. 2019 Jul;71(7):1119-1132. doi: 10.1111/jphp.13097.	`Click`
25	β-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1. Sci Rep. 2016 Feb 12;6:21010. doi: 10.1038/srep21010.	`Click`
26	Combined therapy with EGFR TKI and gambogic acid for overcoming resistance in EGFR-T790M mutant lung cancer. Oncol Lett. 2015 Oct;10(4):2063-2066. doi: 10.3892/ol.2015.3599.	`Click`
27	Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK/p53 and c-met/AKT Signaling Pathways. Front Pharmacol. 2018 Feb 13;9:92. doi: 10.3389/fphar.2018.00092.	`Click`

No.

Title

Href

Amentoflavone Enhances the Therapeutic Efficacy of Sorafenib by Inhibiting Anti-apoptotic Potential and Potentiating Apoptosis in Hepatocellular Carcinoma In Vivo. Anticancer Res. 2018 Apr;38(4):2119-2125. doi: 10.21873/anticanres.12452.

Click

Suppression of AKT Potentiates Synergistic Cytotoxicity of Apigenin with TRAIL in Anaplastic Thyroid Carcinoma Cells. Anticancer Res. 2015 Dec;35(12):6529-37.

Click

Apigenin potentiates TRAIL therapy of non-small cell lung cancer via upregulating DR4/DR5 expression in a p53-dependent manner. Sci Rep. 2016 Oct 18;6:35468. doi: 10.1038/srep35468.

Click

Artesunate exhibits synergistic anti-cancer effects with cisplatin on lung cancer A549 cells by inhibiting MAPK pathway. Gene. 2021 Jan 15;766:145134. doi: 10.1016/j.gene.2020.145134.

Click

β-elemene enhances both radiosensitivity and chemosensitivity of glioblastoma cells through the inhibition of the ATM signaling pathway. Oncol Rep. 2015 Aug;34(2):943-51. doi: 10.3892/or.2015.4050.

Click

Combination of Biochanin A and Temozolomide Impairs Tumor Growth by Modulating Cell Metabolism in Glioblastoma Multiforme. Anticancer Res. 2019 Jan;39(1):57-66. doi: 10.21873/anticanres.13079.

Click

Down-regulation of Cbl-b by bufalin results in up-regulation of DR4/DR5 and sensitization of TRAIL-induced apoptosis in breast cancer cells. J Cancer Res Clin Oncol. 2012 Aug;138(8):1279-89. doi: 10.1007/s00432-012-1204-4.

Click

Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro. Cell Physiol Biochem. 2018;48(4):1433-1442. doi: 10.1159/000492253.

Click

Chlorogenic Acid Enhances Doxorubicin-Mediated Cytotoxic Effect in Osteosarcoma Cells. Int J Mol Sci. 2021 Aug 10;22(16):8586. doi: 10.3390/ijms22168586.

Click

Chlorogenic acid enhances the effects of 5-fluorouracil in human hepatocellular carcinoma cells through the inhibition of extracellular signal-regulated kinases. Anticancer Drugs. 2015 Jun;26(5):540-6. doi: 10.1097/CAD.0000000000000218.

Click

Combination of chrysin and cisplatin promotes the apoptosis of Hep G2 cells by up-regulating p53. Chem Biol Interact. 2015 May 5;232:12-20. doi: 10.1016/j.cbi.2015.03.003.

Click

Doxorubicin has a synergistic cytotoxicity with cucurbitacin B in anaplastic thyroid carcinoma cells. Tumour Biol. 2017 Feb;39(2):1010428317692252. doi: 10.1177/1010428317692252.

Click

Curcumin sensitizes human lung cancer cells to apoptosis and metastasis synergistically combined with carboplatin. Exp Biol Med (Maywood). 2015 Nov;240(11):1416-25. doi: 10.1177/1535370215571881.

Click

The role of daurisoline treatment in hepatocellular carcinoma: Inhibiting vasculogenic mimicry formation and enhancing sensitivity to sorafenib. Phytomedicine. 2021 Nov;92:153740. doi: 10.1016/j.phymed.2021.153740.

Click

XIAP inhibition and generation of reactive oxygen species enhances TRAIL sensitivity in inflammatory breast cancer cells. Mol Cancer Ther. 2012;11(7):1518-1527. doi:10.1158/1535-7163.MCT-11-0787

Click

Emodin and Its Combination with Cytarabine Induce Apoptosis in Resistant Acute Myeloid Leukemia Cells in Vitro and in Vivo. Cell Physiol Biochem. 2018;48(5):2061-2073. doi: 10.1159/000492544.

Click

Fisetin, a phytochemical, potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells. Oncotarget. 2015 Sep 29;6(29):28296-311. doi: 10.18632/oncotarget.5064.

Click

Gambogic acid synergistically potentiates cisplatin-induced apoptosis in non-small-cell lung cancer through suppressing NF-κB and MAPK/HO-1 signalling. Br J Cancer. 2014 Jan 21;110(2):341-52. doi: 10.1038/bjc.2013.752.

Click

Downregulation of BCL2 by AT-101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner. Br J Haematol. 2012 Apr;157(1):59-66. doi: 10.1111/j.1365-2141.2011.08984.x.

Click

Honokiol augments the anti-cancer effects of oxaliplatin in colon cancer cells. Acta Biochim Biophys Sin (Shanghai). 2013 Sep;45(9):773-9. doi: 10.1093/abbs/gmt071.

Click

Licochalcone B induces DNA damage, cell cycle arrest, apoptosis, and enhances TRAIL sensitivity in hepatocellular carcinoma cells. Chem Biol Interact. 2022 Sep 25;365:110076. doi: 10.1016/j.cbi.2022.110076.

Click

Sulforaphene-Carboplatin Combination Synergistically Enhances Apoptosis by Disruption of Mitochondrial Membrane Potential and Cell Cycle Arrest in Human Non-Small Cell Lung Carcinoma. J Med Food. 2016 Sep;19(9):860-9. doi: 10.1089/jmf.2016.3675.

Click

Sulforaphene Enhances The Efficacy of Photodynamic Therapy In Anaplastic Thyroid Cancer Through Ras/RAF/MEK/ERK Pathway Suppression. J Photochem Photobiol B. 2018 Feb;179:46-53. doi: 10.1016/j.jphotobiol.2017.12.013.

Click

Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid. J Pharm Pharmacol. 2019 Jul;71(7):1119-1132. doi: 10.1111/jphp.13097.

Click

β-elemene sensitizes hepatocellular carcinoma cells to oxaliplatin by preventing oxaliplatin-induced degradation of copper transporter 1. Sci Rep. 2016 Feb 12;6:21010. doi: 10.1038/srep21010.

Click

Combined therapy with EGFR TKI and gambogic acid for overcoming resistance in EGFR-T790M mutant lung cancer. Oncol Lett. 2015 Oct;10(4):2063-2066. doi: 10.3892/ol.2015.3599.

Click

Scutellarin Increases Cisplatin-Induced Apoptosis and Autophagy to Overcome Cisplatin Resistance in Non-small Cell Lung Cancer via ERK/p53 and c-met/AKT Signaling Pathways. Front Pharmacol. 2018 Feb 13;9:92. doi: 10.3389/fphar.2018.00092.

Click

Name	Mitogen-activated protein kinase 3
UniProt ID	MK03_HUMAN
Gene Name	MAPK3
Gene ID	5595
Synonyms	MAPK3, ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1, P44MAPK, PRKM3, p44-ERK1, p44-MAPK
Sequence	MAAAAAQGGGGGEPRRTEGVGPGVPGEVEMVKGQPFDVGPRYTQLQYIGEGAYGMVSSAY DHVRKTRVAIKKISPFEHQTYCQRTLREIQILLRFRHENVIGIRDILRASTLEAMRDVYI VQDLMETDLYKLLKSQQLSNDHICYFLYQILRGLKYIHSANVLHRDLKPSNLLINTTCDL KICDFGLARIADPEHDHTGFLTEYVATRWYRAPEIMLNSKGYTKSIDIWSVGCILAEMLS NRPIFPGKHYLDQLNHILGILGSPSQEDLNCIINMKARNYLQSLPSKTKVAWAKLFPKSD SKALDLLDRMLTFNPNKRITVEEALAHPYLEQYYDPTDEPVAEEPFTFAMELDDLPKERL KELIFQETARFQPGVLEAP
Pathway Map	`MAP LINK`
T.C. Number	9.A.14.8.3
KEGG ID	hsa5595
TTD ID	T23276
Pfam	PF00069; PF01633; PF01636; PF03109; PF06293; PF07714; PF12330; PF13095

Pair Name	Amentoflavone, Sorafenib
Phytochemical	Amentoflavone
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Our results demonstrated that amentoflavone significantly enhanced sorafenib-inhibited tumor growth and expression of ERK/AKT phosphorylation and anti-apoptotic proteins compared to single-agent treatment. Additionally, amentoflavone also triggered sorafenib-induced apoptosis through extrinsic and intrinsic apoptotic pathways.

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Phytochemical	Apigenin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Apigenin synergizes with TRAIL through regulation of Bcl2 family proteins in inducing cytotoxicity, and suppression of AKT potentiates synergistic cytotoxicity of apigenin with TRAIL in ATC cells

Pair Name	Apigenin, TNF-related apoptosis inducing ligand
Phytochemical	Apigenin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Expression
Result	Apigenin enhances TRAIL-induced antitumor activity in NSCLC cells by APG via inhibition of the NF-kappaB, AKT and ERK prosurvival regulators

Pair Name	Artesunate, Cisplatin
Phytochemical	Artesunate
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	ART exhibited significant anti-tumor effect on A549 cells and this efficiency could be enhanced by combination with CIS

Pair Name	Beta-Elemene, Temozolomide
Phytochemical	Beta-Elemene
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Expression
Result	These results revealed that β-elemene could significantly increase the radiosensitivity and chemosensitivity of GBM. β-elemene may be used as a potential drug in combination with the radiotherapy and chemotherapy of GBM

Pair Name	Biochanin A, Temozolomide
Phytochemical	Biochanin A
Drug	Temozolomide
Disease Info	[ICD-11: 2A00]	Glioblastoma multiforme	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Chanin A significantly enhanced the anticancer efficacy of temozolomide in GBM cells.

Pair Name	Bufalin, TNF-related apoptosis inducing ligand
Phytochemical	Bufalin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Expression
Result	Bufalin enhanced TRAIL-induced apoptosis by up-regulating the expression of DR4 and DR5. Bufalin-induced down-regulation of Cbl-b contributed to the up-regulation of DR4 and DR5, which might be partially mediated by the activation of ERK, JNK and p38 MAPK.

Pair Name	Caffeic acid, Paclitaxel
Phytochemical	Caffeic acid
Drug	Paclitaxel
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Our results indicated that CA inhibited NSCLC H1299 cell growth by inducing apoptosis and CA and PTX combined produced a synergistic anti-cancer effect in H1299 cells.

Pair Name	Chlorogenic acid, Doxorubicin
Phytochemical	Chlorogenic acid
Drug	Doxorubicin
Disease Info	[ICD-11: 2B51]	Osteosarcoma	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	These findings firstly propose CGA as a promising chemosensitizer and cardioprotective agent in OS therapy, suggesting the p44/42 MAPK pathway as relevantly involved in CGA-mediated Doxo susceptibility.

Pair Name	Chlorogenic acid, Fluorouracil
Phytochemical	Chlorogenic acid
Drug	Fluorouracil
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Expression
Result	CGA sensitizes hepatocellular carcinoma cells to 5-FU treatment by the suppression of ERK activation through the overproduction of ROS. CGA has shown potential as a chemosensitizer of 5-FU chemotherapy in hepatocellular carcinoma.

Pair Name	Chrysin, Cisplatin
Phytochemical	Chrysin
Drug	Cisplatin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Expression
Result	Our results suggest that combination of chrysin and cisplatin is a promising strategy for chemotherapy of human cancers that are resistant to cisplatin.

Pair Name	Cucurbitacin B, Doxorubicin
Phytochemical	Cucurbitacin B
Drug	Doxorubicin
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Synergistic cytotoxicity of doxorubicin with cucurbitacin B is mediated by B-cell chronic lymphocytic leukemia/lymphoma 2 family proteins, survivin, and reactive oxygen species and modulated by Janus kinase 2/signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 in anaplastic thyroid carcinoma cells.

Pair Name	Curcumin, TNF-related apoptosis inducing ligand
Phytochemical	Curcumin
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Combined treatment with curcumin and carboplatin inhibited tumor cell growth, migration, and invasion compared with either drug alone. The synergistic antitumor activity of curcumin combined with carboplatin is mediated by multiple mechanisms involving suppression of NF-kappaB via inhibition of the Akt/IKKalpha pathway and enhanced ERK1/2 activity

Pair Name	Daurinoline, Sorafenib
Phytochemical	Daurinoline
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Our study provides insights into the molecular mechanisms underlying DS-induced inhibition of VM, which may facilitate the development of a novel clinical anti-HCC drug. Moreover, our findings suggest that the combination of DS and sorafenib constitutes a potential therapeutic strategy for HCC.

Pair Name	Embelin, TRAIL
Phytochemical	Embelin
Drug	TRAIL
Disease Info	[ICD-11: 2C60]	Breast cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Expression
Result	Embelin primes IBC cells for TRAIL-mediated apoptosis by its direct action on the anti-caspase activity of XIAP and by shifting the cellular redox balance toward oxidative stress–mediated apoptosis

Pair Name	Emodin, Cytarabine
Phytochemical	Emodin
Drug	Cytarabine
Disease Info	[ICD-11: 2A60.Z]	Acute myeloid leukemia	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Emodin and its combination with Ara-C may be considered a promising therapeutic approach in AML and worthy of further investigation.

Pair Name	Fisetin, Sorafenib
Phytochemical	Fisetin
Drug	Sorafenib
Disease Info	[ICD-11: 2C30]	Melanoma	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Expression
Result	Fisetin potentiates sorafenib-induced apoptosis and abrogates tumor growth in athymic nude mice implanted with BRAF-mutated melanoma cells.

Pair Name	Gambogic Acid, Cisplatin
Phytochemical	Gambogic Acid
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Gambogic acid sensitises lung cancer cells to CDDP in vitro and in vivo in NSCLC through inactivation of NF-κB and MAPK/HO-1 signalling pathways, providing a rationale for the combined use of CDDP and GA in lung cancer chemotherapy.

Pair Name	Gossypol, lenalidomide
Phytochemical	Gossypol
Drug	lenalidomide
Disease Info	[ICD-11: 2A82]	Chronic lymphocytic leukemia	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Downregulation of BCL2 by AT-101 enhances the antileukaemic effect of lenalidomide both by an immune dependant and independent manner.

Pair Name	Honokiol, Oxaliplatin
Phytochemical	Honokiol
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B90]	Colon cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Expression
Result	This combination allows a reduction in oxaliplatin dose, and thereby reduces its adverse effects. It may also enhance the chemotherapeutic effect of oxaliplatin for this disease.

Pair Name	Licochalcone B, TNF-related apoptosis inducing ligand
Phytochemical	Licochalcone B
Drug	TNF-related apoptosis inducing ligand
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	LCB exhibits cytotoxic activity through modulation of the Akt/mTOR, ER stress and MAPK pathways in HCC cells and effectively enhances TRAIL sensitivity through the upregulation of DR5 expression in ERK- and JNK-dependent manner. Combination therapy with LCB and TRAIL may be an alternative treatment strategy for HCC.

Pair Name	Sulforaphene, Carboplatin
Phytochemical	Sulforaphene
Drug	Carboplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	This study demonstrates that the duel character of this combination therapy may be an effective replacement for conventional therapy alone against NSCLC.

Pair Name	Sulforaphene, Photodynamic therapy
Phytochemical	Sulforaphene
Drug	Photodynamic therapy
Disease Info	[ICD-11: 2D10.Z]	Thyroid cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Our work designates sulforaphene as a unique natural enhancer of efficacy with PDT against anaplastic thyroid cancer.

Pair Name	Usnic acid, Sorafenib
Phytochemical	Usnic acid
Drug	Sorafenib
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Expression
Result	Investigation of new treatment option for hepatocellular carcinoma: a combination of sorafenib with usnic acid

Pair Name	Beta-Elemene, Oxaliplatin
Phytochemical	Beta-Elemene
Drug	Oxaliplatin
Disease Info	[ICD-11: 2B91]	Colorectal cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Our findings show that β-elemene can block the reduction of CTR1 resulting from oxaliplatin treatment, and therefore has a synergistic anti-HCC effect with oxaliplatin by enhancing cellular uptake of oxaliplatin. The synergistic effects of β-elemene and oxaliplatin deserve further evaluation in clinical settings.

Pair Name	Gambogic Acid, Gefitinib
Phytochemical	Gambogic Acid
Drug	Gefitinib
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Down-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	Gefitinib in combination with GA resulted in antitumor growth in the EGFR-T790M secondary mutation NCI-H1975 tumor model due to an enhanced apoptotic effect. This novel therapeutic strategy may be a practical approach for the treatment of patients who show gefitinib resistance.

Pair Name	Scutellarin, Cisplatin
Phytochemical	Scutellarin
Drug	Cisplatin
Disease Info	[ICD-11: 2C25]	Lung cancer	Investigative
Regulate Info	Up-regulation	Mitogen-activated protein kinase 3	Phosphorylation
Result	This study identifies the unique role of scutellarin in reversing cisplatin resistance through apoptosis and autophagy, and suggests that combined cisplatin and scutellarin might be a novel therapeutic strategy for patients with NSCLC.