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1,8-dihydroxy-3-carboxyl-9,10-anthraquinone, 4,5-dihydroxyanthraquinone-2-carboxylic acid, dipropionyl rhein, rhein

No.	Title	Href
1	Inhibition of PI3K/AKT signaling via ROS regulation is involved in Rhein-induced apoptosis and enhancement of oxaliplatin sensitivity in pancreatic cancer cells. Int J Biol Sci. 2021 Jan 15;17(2):589-602. doi: 10.7150/ijbs.49514.	`Click`
2	Synergistic antitumor effects of rhein and doxorubicin in hepatocellular carcinoma cells. J Cell Biochem. 2020 Oct;121(10):4009-4021. doi: 10.1002/jcb.27514.	`Click`
3	Organic anion transporters and PI3K-AKT-mTOR pathway mediate the synergistic anticancer effect of pemetrexed and rhein. J Cell Physiol. 2020 Apr;235(4):3309-3319. doi: 10.1002/jcp.29218.	`Click`
4	Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C. Cancer Res. 2003 Aug 15;63(16):5118-25.	`Click`

No.

Title

Href

Inhibition of PI3K/AKT signaling via ROS regulation is involved in Rhein-induced apoptosis and enhancement of oxaliplatin sensitivity in pancreatic cancer cells. Int J Biol Sci. 2021 Jan 15;17(2):589-602. doi: 10.7150/ijbs.49514.

Click

Synergistic antitumor effects of rhein and doxorubicin in hepatocellular carcinoma cells. J Cell Biochem. 2020 Oct;121(10):4009-4021. doi: 10.1002/jcb.27514.

Click

Organic anion transporters and PI3K-AKT-mTOR pathway mediate the synergistic anticancer effect of pemetrexed and rhein. J Cell Physiol. 2020 Apr;235(4):3309-3319. doi: 10.1002/jcp.29218.

Click

Rottlerin sensitizes colon carcinoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis via uncoupling of the mitochondria independent of protein kinase C. Cancer Res. 2003 Aug 15;63(16):5118-25.

Click

Name	Rhein
PubChem CID	10168
Molecular Weight	284.22g/mol
Synonyms	1,8-dihydroxy-3-carboxyl-9,10-anthraquinone, 4,5-dihydroxyanthraquinone-2-carboxylic acid, dipropionyl rhein, rhein
Formula	C₁₅H₈O₆
SMILES	C1=CC2=C(C(=C1)O)C(=O)C3=C(C2=O)C=C(C=C3O)C(=O)O
InChI	1S/C15H8O6/c16-9-3-1-2-7-11(9)14(19)12-8(13(7)18)4-6(15(20)21)5-10(12)17/h1-5,16-17H,(H,20,21)
InChIKey	FCDLCPWAQCPTKC-UHFFFAOYSA-N
CAS Number	478-43-3
ChEMBL ID	CHEMBL418068
ChEBI ID	CHEBI:8825
Herb ID	HBIN042199
Drug Bank ID	DB13174
KEGG ID	C10401
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	HuZhang
Use Part	Rhizome
Habitat	Shaanxi, GanSu, JiangSu, ZheJiang, AnHui, FuJian, JiangXi, ShanDong, ShangHai, HeNan, HuBei, HuNan, SiChuan
Flavor	Mildly bitter
Meridian Tropism	Liver, Gallbladder, Lung
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Caryophyllales 　　　　-->Family: Polygonaceae 　　　　　-->Genus: Persicaria 　　　　　　-->Species: Polygonum cuspidatum

Chineses Pinyin	ZhangYeDaHuang
Use Part	Root and rhizome
Habitat	GanSu, SiChuan, QingHai, YunNan, XiZang
Species	>Kingdom: Viridiplantae 　-->Phylum: Streptophyta 　　-->Class: Equisetopsida 　　　-->Order: Caryophyllales 　　　　-->Family: Polygonaceae 　　　　　-->Genus: Rheum 　　　　　　-->Species: Rheum palmatum

Pair Name	Rhein, Oxaliplatin
Partner Name	Oxaliplatin
Disease Info	[ICD-11: 2C10]	Pancreatic cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Down-regulation	Expression	PIK3CA	hsa5290
	Up-regulation	Expression	ROS1	hsa6098
In Vitro Model	PANC-1	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0480
In Vitro Model	MIA PaCa-2	Pancreatic ductal adenocarcinoma	Homo sapiens (Human)	CVCL_0428
Result	These data demonstrate that Rhein can induce apoptosis and enhance the oxaliplatin sensitivity of PC cells, suggesting that Rhein may be an effective strategy to overcome drug resistance in the chemotherapeutic treatment of PC.

Pair Name	Rhein, Doxorubicin
Partner Name	Doxorubicin
Disease Info	[ICD-11: 2C12]	Hepatocellular carcinoma		Investigative
Gene Regulation	Up-regulation	Activity	CASP3	hsa836
In Vitro Model	SMMC-7721	Human papillomavirus-related cervical adenocarcinoma	Homo sapiens (Human)	CVCL_0534
In Vitro Model	Hep-G2	Hepatoblastoma	Homo sapiens (Human)	CVCL_0027
Result	Our data indicate that a decline in mitochondrial energy metabolism was responsible for the synergistic antitumor effects of rhein and DOX in hepatocellular carcinoma cells. Reduction of ΔΨm and opening of mPTP inhibited the exchange of ATP/adenosine diphosphate between mitochondrial matrix and cytoplasm is the important mechanism.

Pair Name	Rhein, Pemetrexed
Partner Name	Pemetrexed
Disease Info	[ICD-11: 2C25]	Lung cancer		Investigative
Biological Phenomena	Induction-->Autophagy
Gene Regulation	Down-regulation	Expression	AKT1	hsa207
	Up-regulation	Expression	MAP1LC3B	hsa81631
	Down-regulation	Expression	MTOR	hsa2475
	Down-regulation	Expression	PIK3CA	hsa5290
	Up-regulation	Phosphorylation	PRKAA1	hsa5562
In Vitro Model	A-549	Lung adenocarcinoma	Homo sapiens (Human)	CVCL_0023
Result	Our findings demonstrated that the potential application of rhein as a candidate drug in combination with PTX is promising for treatment of the human lung cancer.

Pair Name	Rhein, Calphostin c
Partner Name	Calphostin c
Disease Info	[ICD-11: 2B90]	Colon cancer		Investigative
Biological Phenomena	Induction-->Apoptosis
Gene Regulation	Down-regulation	Expression	XIAP	hsa331
In Vitro Model	HCT 116	Colon carcinoma	Homo sapiens (Human)	CVCL_0291
In Vitro Model	RKO	Colon carcinoma	Homo sapiens (Human)	CVCL_0504
Result	Data suggest that rottlerin affects mitochondrial function independent of PKC delta, thereby sensitizing cells to TRAIL, and that mitochondria constitute an important target in overcoming inherent resistance to TRAIL in colon carcinomas.