Disease relevance of Rheum emodin

• Suppressed transformation and induced differentiation of HER-2/neu-overexpressing breast cancer cells by emodin [1].
• Our work indicates a new mechanism for the emodin-mediated anticancer effect and justifies further investigation of emodin as a therapeutic and preventive agent for prostate cancer [2].
• The selected clones were expressed in Escherichia coli (BM 25.8 line) and were further screened for biosynthesis of emodin to hypericin, which resulted in an 84.6% conversion [3].
• Furthermore, the combination of emodin with cisplatin, doxorubicin or etoposide (VP16) synergistically inhibited the proliferation of HER-2/neu-overexpressing lung cancer cells, whereas low doses of emodin, cisplatin, doxorubicin, or VP16 alone had only minimal antiproliferative effects on these cells [4].
• In vivo study showed that emodin made the EC/CUHK1 cell-derived tumors more sensitive to arsenic trioxide with no additional systemic toxicity and side effects [5].

High impact information on Rheum emodin

• Therefore, data from this study provide novel evidence that emodin inhibits cell adhesion and spreading through disruption of the membrane lipid raft-associated integrin signaling pathway [6].
• Emodin inhibits tumor cell adhesion through disruption of the membrane lipid Raft-associated integrin signaling pathway [6].
• Emodin down-regulates androgen receptor and inhibits prostate cancer cell growth [2].
• Therefore, we concluded that emodin sensitized HeLa cells to As(2)O(3) via generation of ROS and ROS-mediated inhibition on two major prosurvival transcription factors, nuclear factor kappaB and activator protein 1 [7].
• These results may have chemotherapeutic implications for using emodin to target HER-2/neu-overexpressing cancer cells [1].

Chemical compound and disease context of Rheum emodin

• Tyrosine kinase inhibitor emodin suppresses growth of HER-2/neu-overexpressing breast cancer cells in athymic mice and sensitizes these cells to the inhibitory effect of paclitaxel [8].
• Fifty-one new C-methyl-modified derivatives of the anthraquinones chrysophanol and emodin or their various methyl ethers were prepared for structure-activity relationship studies of anticancer activity against mouse leukemia L1210 and human leukemia HL-60 cells [9].
• Inhibition of electron transfer and uncoupling effects by emodin and emodinanthrone in Escherichia coli [10].
• Emodin (1,6,8-trihydroxy-3-methylanthraquinone), an important aglycone found in natural anthraquinone glycosides frequently used in laxative drugs, was mutagenic in the Salmonella/mammalian microsome assay (Ames test) with a specificity for strain TA1537 [11].
• Emodin markedly decreased the average kidney weight/body weight, glomerular area, glomerular volume and all biochemical indexes (P<0.05), having a weak action on the level of blood glucose [12].

Biological context of Rheum emodin

• Here, we first found that emodin significantly inhibited cell adhesion of various human cancer cells [6].
• Emodin enters the nucleotide binding site of the enzyme, filling a hydrophobic pocket between the N-terminal and the C-terminal lobes, in the proximity of the site occupied by the base rings of the natural co-substrates [13].
• The replacement of ATP by the competitive inhibitor emodin induces conformational modifications in the catalytic site of protein kinase CK2 [13].
• In this study a novel red-color-based colony screening method for examining a cDNA library (lambda-TriplEX2) derived from H. perforatum cell cultures revealed the gene responsible for hypericin biosynthesis after the administration of emodin, a precursor of hypericin [3].
• In contrast, emodin, which blocks phosphorylation of her2/neu by heregulin, failed to reduce NF-kappaB activation [14].

Anatomical context of Rheum emodin

• In the present study we investigated the effects of emodin on the activation of NF-kappaB in human umbelical vein endothelial cells (EC) [15].
• Since the promoter regions of ICAM-1, VCAM-1, and ELAM-1 contain NF-kappaB binding sites and these adhesion molecules are involved in the attachment of leukocytes to EC, the effect of emodin on the adhesion of monocytes to EC and the expression of these adhesion molecules was also studied [15].
• We found that DK-V-47 is more potent than emodin in suppressing transformation phenotypes of activated HER-2/neu transformed 3T3 cells including anchorage-dependent and -independent growth, metastasis-associated properties [16].
• Our previous studies showed that a naphthoquinone and an anthraquinone (emodin) displayed the capability of producing ROS and facilitating arsenic cytotoxicity in both leukemia and solid tumor cell lines [5].
• We found that emodin (3-methyl-1,6,8-trihydroxyanthraquinone), an active component from the rhizome of Rheum palmatum, significantly inhibited epidermal growth factor (EGF)- induced migration in various human cancer cell lines [17].

Associations of Rheum emodin with other chemical compounds

• A combination of CK2 inhibitors, emodin or 4,5,6,7-tetrabromobenzotriazole, with octreotide was injected intraperitoneally from postnatal (P) day P11 to P17 to block mouse OIR [18].
• The work described here was carried out to examine (1) whether the tyrosine kinase activity of p185neu is required for resistance to chemotherapeutic drugs of HER-2/neu-overexpressing NSCLC cells and (2) whether the tyrosine kinase inhibitor emodin can sensitize these cells to chemotherapeutic drugs [4].
• A group of chrysophanol and emodin derivatives with DNA-intercalating capability and with or without alkylating potential have been synthesized and shown to have antitumor activity in vitro [19].
• Proteasome-dependent degradation of endogenous Id1 in HeLa cells is also stimulated by treatment with curcumin or emodin [20].
• Such induction was ameliorated by emodin (20 microg/mL) (TGF-beta 1 concentration 2.25 +/- 0.15 and 2.96 +/- 0.33 pg/microg cellular protein at 24 hours and 48 hours, respectively, in the presence of emodin and 30 mmol D-glucose; P < 0.001 compared to 30 mmol D-glucose alone at both time points) [21].

Gene context of Rheum emodin

• The inhibitors of CSN associated kinases, curcumin and emodin, significantly induce ubiquitination and proteasome-dependent degradation of transiently expressed Id3 in HeLa cells [20].
• Here, we examine the effects of emodin on vascular endothelial growth factor (VEGF)-A-induced angiogenesis, both in vitro and in vivo [22].
• Emodin inhibits vascular endothelial growth factor-A-induced angiogenesis by blocking receptor-2 (KDR/Flk-1) phosphorylation [22].
• In addition, emodin markedly suppressed EGF-induced activation of Cdc42 and Rac1 and the corresponding cytoskeleton changes [17].
• Among the subunits, the expression of ERCC1 in WI38 cells was up-regulated significantly after emodin treatment [23].

Analytical, diagnostic and therapeutic context of Rheum emodin

• Both immunohistochemical staining and Western blot analysis showed that emodin decreases tyrosine phosphorylation of HER-2/neu in tumor tissue [8].
• Furthermore, the combination of emodin and paclitaxel synergistically inhibited the anchorage-dependent and -independent growth of HER-2/neu-overexpressing breast cancer cells in vitro and synergistically inhibited tumor growth and prolonged survival in athymic mice bearing s.c. xenografts of human tumor cells expressing high levels of p185neu [8].
• The extent of retinal neovascularization in a mouse OIR model was reduced >70% (versus untreated or vehicle-treated groups) after treatment with emodin (6 days at 60 mg/kg per day) and by approximately 60% after treatment at the same dose with TBB, the most specific CK2 inhibitor known [24].
• The gene regulations of the subunits after emodin treatment were determined by reverse transcription-polymerase chain reaction (RT-PCR) using specific primers [23].
• We used electron spin resonance (ESR) and spin trapping techniques to study the light-stimulated redox properties of the emodin derivatives and their GnRH conjugates [25].

References