Aloe

Rich66 · 11-21-2009, 03:07 PM

NOTE: Aloe-emodin may be slightly estrogenic, avoid for now (or get clarification) if ER+

In Vivo. 2009 Jan-Feb;23(1):171-5.
A randomized study of chemotherapy versus biochemotherapy with chemotherapy plus Aloe arborescens in patients with metastatic cancer.

Lissoni P, Rovelli F, Brivio F, Zago R, Colciago M, Messina G, Mora A, Porro G.
Division of Radiation Oncology, St. Gerardo Hospital, Monza, Milan, Italy. p.lissoni@hsgerardo.org
BACKGROUND: The recent advances in the analysis of tumor immunobiology suggest the possibility of biologically manipulating the efficacy and toxicity of cancer chemotherapy by endogenous or exogenous immunomodulating substances. Aloe is one of the of the most important plants exhibiting anticancer activity and its antineoplastic property is due to at least three different mechanisms, based on antiproliferative, immunostimulatory and antioxidant effects. The antiproliferative action is determined by anthracenic and antraquinonic molecules, while the immunostimulating activity is mainly due to acemannan. PATIENTS AND METHODS: A study was planned to include 240 patients with metastatic solid tumor who were randomized to receive chemotherapy with or without Aloe. According to tumor histotype and clinical status, lung cancer patients were treated with cisplatin and etoposide or weekly vinorelbine, colorectal cancer patients received oxaliplatin plus 5-fluorouracil (5-FU), gastric cancer patients were treated with weekly 5-FU and pancreatic cancer patients received weekly gemcitabine. Aloe was given orally at 10 ml thrice/daily. RESULTS: The percentage of both objective tumor regressions and disease control was significantly higher in patients concomitantly treated with Aloe than with chemotherapy alone, as well as the percent of 3-year survival patients. CONCLUSION: This study seems to suggest that Aloe may be successfully associated with chemotherapy to increase its efficacy in terms of both tumor regression rate and survival time.

PMID: 19368145 [PubMed - indexed for MEDLINE]

Nat Immun. 1998;16(1):27-33.
Biotherapy with the pineal immunomodulating hormone melatonin versus melatonin plus aloe vera in untreatable advanced solid neoplasms.

Lissoni P, Giani L, Zerbini S, Trabattoni P, Rovelli F.
Division of Radiation Oncology, San Gerardo Hospital, Monza, Milan, Italy.
The possibility of natural cancer therapy has been recently suggested by advances in the knowledge of tumor immunobiology. Either cytokines such as IL-2, or neurohormones, such as the pineal indole melatonin (MLT), may activate anticancer immunity. In addition, immunomodulating substances have also been isolated from plants, particularly from Aloe vera. Preliminary clinical studies had already shown that MLT may induce some benefits in untreatable metastatic solid tumor patients, whereas, for the time being, no clinical trial has been performed with aloe products. We have carried out a clinical study to evaluate whether the concomitant administration of aloe may enhance the therapeutic results of MLT in patients with advanced solid tumors for whom no effective standard anticancer therapies are available. The study included 50 patients suffering from lung cancer, gastrointestinal tract tumors, breast cancer or brain glioblastoma, who were treated with MLT alone (20 mg/day orally in the dark period) or MLT plus A. vera tincture (1 ml twice/day). A partial response (PR) was achieved in 2/24 patients treated with MLT plus aloe and in none of the patients treated with MLT alone. Stable disease (SD) was achieved in 12/24 and in 7/26 patients treated with MLT plus aloe or MLT alone, respectively. Therefore, the percentage of nonprogressing patients (PR + SD) was significantly higher in the group treated with MLT plus aloe than in the MLT gorup (14/24 vs. 7/26, p < 0.05). The percent 1-year survival was significantly higher in patients treated with MLT plus aloe (9/24 vs. 4/26, p < 0.05). Both treatments were well tolerated. This preliminary study would suggest that natural cancer therapy with MLT plus A. vera extracts may produce some therapeutic benefits, at least in terms of stabilization of disease and survival, in patients with advanced solid tumors, for whom no other standard effective therapy is available.

Cell Mol Life Sci. 2006 Dec;63(24):3083-9.
Evaluation of the anti-angiogenic effect of aloe-emodin.

Cárdenas C, Quesada AR, Medina MA.
Procel Lab, Department of Molecular Biology and Biochemistry, Faculty of Sciences, University of Málaga, 29071, Málaga, Spain.
The present study identified aloe-emodin (AE, a hydroxyanthraquinone from Aloe vera and other plants) as a new anti-angiogenic compound with inhibitory effects in an in vivo angiogenesis assay and evaluates its effects on specific key steps of the angiogenic process. AE inhibits endothelial cell proliferation, but this effect is not cell specific, since AE also inhibits tumor cell proliferation. Cell migration and invasion are not remarkably affected by AE. On the other hand, AE has different effects on endothelial and tumor cell gelatinases. Two main targets of the pharmacological action of AE as an anti-angiogenic compound seem to be urokinase secretion and tubule formation of endothelial cells. Finally, AE produces a remarkable photocytotoxic effect on tumor cells. Taken together, our data indicate that AE can behave both as an anti-tumor and an anti-angiogenic compound and suggest that AE could be a candidate drug for photodynamic therapy.

PMID: 17131052 [PubMed - indexed for MEDLINE]

Ann Oncol. 2009 Aug;20(8):1445-6.
Aloe-induced hypokalemia in a patient with breast cancer during chemotherapy.

Baretta Z, Ghiotto C, Marino D, Jirillo A.
PMID: 19654201 [PubMed - indexed for MEDLINE]

Cancer Biol Ther. 2007 Aug;6(8):1200-5. Epub 2007 May 4.
Antitumor effects of a natural anthracycline analog (Aloin) involve altered activity of antioxidant enzymes in HeLaS3 cells.

Nićiforović A, Adzić M, Spasić SD, Radojcić MB.
Department of Molecular Biology and Endocrinology, VINCA Institute of Nuclear Sciences, Belgrade, Serbia.
The antiproliferative and cytotoxic potential of the natural anthracycline aloin from Aloe vera was tested on human uterine carcinoma HeLaS3 cells. Aloin showed a pronounced antiproliferative effect at physiological concentration (IC50 = 97 microM), caused cell cycle arrest in the S phase and markedly increased HeLaS3 cell apoptosis (to 24%). In the concentration range of 20-100 microM, its action was accompanied by remarkable changes in the activity of almost all antioxidant enzymes: MnSOD activity was increased many fold, while CuZnSOD and iNOS activities were inhibited. Moreover, inhibition of CuZnSOD was shown to occur by direct aloin interaction with the enzyme. As catalase activity was not changed, it is suggested that such conditions were responsible for antiproliferative and cytotoxic effects owing to accumulation of H2O2. Aloin alone was a more potent proapoptotic agent than a 2 Gy fractional dose of ionizing radiation or a combination of the two. Compared to other currently used therapeutics, aloin, due to its less undesirable side effects and antimetastatic potential, may prove to be the agent of choice on which clinical protocols for the treatment of human cervical carcinoma should rely in future.

PMID: 17726368 [PubMed - indexed for MEDLINE]

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 Paclitaxel1

Clinical Cancer Research February 1999 5; 343

+ Author Affiliations

Section of Molecular Cell Biology, Departments of Cancer Biology [L. Z., Y-K. L., W. X., M-C. H.] and Breast Medical Oncology [G. N. H.], The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030

Abstract

Overexpression of the HER-2/neu proto-oncogene, which encodes the tyrosine kinase receptor p185^neu, has been observed in tumors from breast cancer patients. We demonstrated previously that emodin, a tyrosine kinase inhibitor, suppresses tyrosine kinase activity in HER-2/neu-overexpressing breast cancer cells and preferentially represses transformation phenotypes of these cells in vitro. In the present study, we examined whether emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and whether emodin can sensitize these tumors to paclitaxel, a commonly used chemotherapeutic agent for breast cancer patients. We found that emodin significantly inhibited tumor growth and prolonged survival in mice bearing HER-2/neu-overexpressing human breast cancer cells. 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 p185^neu. Both immunohistochemical staining and Western blot analysis showed that emodin decreases tyrosine phosphorylation of HER-2/neu in tumor tissue. Taken together, our results suggest that the tyrosine kinase activity of HER-2/neu is required for tumor growth and chemoresistance and that tyrosine kinase inhibitors such as emodin can inhibit the growth of HER-2/neu-overexpressing tumors in mice and also sensitize these tumors to paclitaxel. The results may have important implications in chemotherapy for HER-2/neu-overexpressing breast tumors.

Arch Pharm Res. 2008 Jun;31(6):722-6. Epub 2008 Jun 19.
Anti-proliferative effects of estrogen receptor-modulating compounds isolated from Rheum palmatum.

Kang SC, Lee CM, Choung ES, Bak JP, Bae JJ, Yoo HS, Kwak JH, Zee OP.
Gyeonggi Pharmaceutical Research Center, Suwon, 443-766, Korea.
The Rheum palmatum L., a traditional medicine in Korea, was screened for their estrogenic activity in a recombinant yeast system with a human estrogen receptor (ER) expression plasmid and a reporter plasmid used in a previous study. The EC50 values of the n-hexane, dichloromethane, ethyl acetate, n-butanol, and water fractions of the methanolic extract of R. palmatum in the yeast-based estrogenicity assay system were 0.145, 0.093, 0.125, 1.459, 2.853 microg/mL, respectively, with marked estrogenic activity in the dichloromethane fraction. Using an activity-guided fractionation approach, five known anthraquinones, chrysophanol (1), physcion (2), emodin (3), aloe-emodin (4) and rhein (5), were isolated from the dichloromethane fraction. Compound 3 had the highest estrogenic relative potency (RP, 17bestradiol = 1.00) (6.3 x 10(-2)), followed by compound 4 (3.8 x 10(-3)), compound 5 (2.6 x 10(-4)), a compound 1 (2.1 x 10(-4)). Also, compound 3 and fraction 3 (which contained compound 3) of the dichloromethane fraction of R. palmatum showed strong cytotoxicity in both ER-positive (MCF-7) and-negative (MDA-MB-231) breast cancer cell lines.

PMID: 18563353 [PubMed - indexed for MEDLINE]

Cancer Biol Ther. 2006 Jan;5(1):97-103. Epub 2006 Jan 22.
Cytotoxicity of a natural anthraquinone (Aloin) against human breast cancer cell lines with and without ErbB-2: topoisomerase IIalpha coamplification.

Esmat AY, Tomasetto C, Rio MC.
Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, Egypt. amyesmat@yahoo.com
In the present study the cytotoxic activity of aloin, a natural anthracycline from Aloe plant, is reported against two human breast cancer cell lines; without (MCF-7) and with (SKBR-3) erbB-2-topoIIalpha coamplification. MCF-7cell line was shown to be more sensitive to aloin than SKBR-3 demonstrated by MTT and clonogenic assays, from which IC50 and 50% ICF values are reported to be 60 microg/ml, respectively, in the former cell line and as high as 150 and 80 microg/ml, respectively, in the latter, which are still far below the maximum tolerated dose of the compound. The effect of aloin is suggested to be brought about by more than one mechanism depending on the dose level and tumor phenotype. This was demonstrated by flow cytometric analysis, fluorescence microscopy and western blot analysis, which revealed that aloin at higher concentrations caused a reduction in the proportion of cells undergoing mitosis by induction of apoptosis, inhibition of topo II alpha protein expression and downregulation of cyclin B1 protein expression in MCF-7 cell line, whereas erbB-2 protein expression was not affected. Topo IIalpha protein expression was mildly downregulated in SKBR-3 cell line at higher concentrations only.

PMID: 16357514 [PubMed - indexed for MEDLINE]

Biochem Pharmacol. 2009 Jun 1;77(11):1674-83. Epub 2009 Mar 11.
Potentiation of the effect of gemcitabine by emodin in pancreatic cancer is associated with survivin inhibition.

Guo Q, Chen Y, Zhang B, Kang M, Xie Q, Wu Y.
Department of Surgery, The Second Affiliated Hospital, Zhejiang University College of Medicine, Cancer Institute of Zhejiang University, #88 Jiefang Road, Hangzhou City, 310009, PR China.
Pancreatic cancer is one human malignancy which has chemoresistant behavior to gemcitabine treatment. In this study, we revealed that emodin, an active component from Chinese medicinal herbs, could enhance pancreatic cancer cells apoptosis induced by gemcitabine.demonstrated survivin expression could be up-regulated by gemcitabine. Surprisingly, survivin expression induced by gemcitabine could be inhibited in combination with emodin treatment. Survivin, a member of the inhibitor of apoptosis gene family, is involved in control of cell division and inhibition of apoptosis and described as a beta-catenin/Tcf/Lef target gene. Western blot and PCR analysis showed that emodin suppressed survivin expression in a dose- and time-dependent manner. Moreover, cells treated with gemcitabine and emodin showed a preferential peri-plasmamembrane position of beta-catenin, blocking the translocation of beta-catenin to nucleus induced by gemcitabine. In addition to these in vitro results, we also found that emodin potentiates the antitumor effects of gemcitabine in vivo by down-regulating the expression of survivin and beta-catenin. Taken together, these results suggest that emodin potentiates gemcitabine antitumor activity through suppression of survivin gene in pancreatic cancer.

PMID: 19428321 [PubMed - indexed for MEDLINE]

Cancer Biother Radiopharm. 2008 Apr;23(2):222-8.
The effect of emodin on VEGF receptors in human colon cancer cells.

Lu Y, Zhang J, Qian J.
Department of Hepatology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
AIMS: This study was designed to evaluate the antiangiogenic properties of emodin and its ability to inhibit tyrosine-kinase-mediated phosphorylation of vascular endothelial growth factor (VEGF) receptors in colon cancer cells. METHODS: The effects of emodin on VEGF-receptor (VEGFR) phosphorylation were determined by assaying the tyrosine kinase activity and by Western blot analysis. The antiproliferative and proapoptotic activities of emodin were evaluated by soft agar colony formation, flow cytometric analysis of cell cycle, and by apoptotic assay. RESULTS: Emodin causes a dose-dependent inhibition of VEGFR phosphorylation in colon cancer cells. Treatment with 40 muM of emodin decreased the relative activity of VEGFR-1 to 22.4%, when compared to the control group (assigned a value of 100%); VEGFR-2 and -3 showed a similar reduction in relative activity at 58.5% and 31.6%, respectively (p < 0.01, in each case). Treatment with emodin reduced VEGFR phosphorylation, as evidenced by Western blot analysis. Flow cytometric analysis showed that, upon treatment with emodin, the HCT116 cell cycle was blocked at the G2/M phase. Emodin also increased the apoptosis of HCT116 cells in a dose-dependent manner; treatment with 40 muM emodin increased the apoptotic rate from 8.1% +/- 2.7% in the control group to 27.8% +/- 10.9% in the treated group (p < 0.01). CONCLUSIONS: These studies demonstrate that emodin may inhibit cancer-cell growth by blocking VEGFR signaling and indicate that emodin can be used as a potential inhibitor for tumor angiogenesis.

Med Res Rev. 2007 Sep;27(5):591-608.
Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent.

Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P.
Department of Biochemistry, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Thiruvananthapuram 695011, India. srinivasg@sctimst.ac.in
Anthraquinones represent a large family of compounds having diverse biological properties. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a naturally occurring anthraquinone present in the roots and barks of numerous plants, molds, and lichens, and an active ingredient of various Chinese herbs. Earlier studies have documented mutagenic/genotoxic effects of emodin, mainly in bacterial system. Emodin, first assigned to be a specific inhibitor of the protein tyrosine kinase p65lck, has now a number of cellular targets interacting with it. Its inhibitory effect on mammalian cell cycle modulation in specific oncogene overexpressed cells formed the basis of using this compound as an anticancer agent. Identification of apoptosis as a mechanism of elimination of cells treated with cytotoxic agents initiated new studies deciphering the mechanism of apoptosis induced by emodin. At present, its role in combination chemotherapy with standard drugs to reduce toxicity and to enhance efficacy is pursued vigorously. Its additional inhibitory effects on angiogenic and metastasis regulatory processes make emodin a sensible candidate as a specific blocker of tumor-associated events. Additionally, because of its quinone structure, emodin may interfere with electron transport process and in altering cellular redox status, which may account for its cytotoxic properties in different systems. However, there is no documentation available which reviews the biological activities of emodin, in particular, its growth inhibitory effects. This review is an attempt to analyze the biological properties of emodin, a molecule offering a broad therapeutic window, which in future may become a member of anticancer armamentarium. (c) 2006 Wiley Periodicals, Inc.

PMID: 17019678 [PubMed - indexed for MEDLINE]
Article purchase: LINK

Bioorg Med Chem Lett. 2001 Jul 23;11(14):1839-42.
Phytoestrogens from the roots of Polygonum cuspidatum (Polygonaceae): structure-requirement of hydroxyanthraquinones for estrogenic activity.

Matsuda H, Shimoda H, Morikawa T, Yoshikawa M.
Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, 607-8412, Kyoto, Japan.
The methanolic extract from the roots of Polygonum (P.) cuspidatum was found to enhance cell proliferation at 30 or 100 microg/mL in MCF-7, an estrogen-sensitive cell line. By bioassay-guided separation from P. cuspidatum with the most potent activity, emodin and emodin 8-O-beta-D-glucopyranoside were isolated as active principles. The methanolic extracts from Polygonum, Cassia, Aloe, and Rheum species, which were known to contain anthraquinones, also showed the MCF-7 proliferation. As a result of the evaluation of various anthraquinones from plant sources and synthetic anthraquinones, aloe-emodin, chrysophanol, chrysophanol 8-O-beta-D-glucopyranoside, and 1,8-dihydroxyanthraquinone showed weak activity. On the other hand, alizalin and 2,6-dihydroxyanthraquinone as well as emodin having the 2- and/or 6-hydroxyl groups showed potent activity. These results show that the unchelated hydroxyl group is essential for strong activity. Emodin and 2,6-dihydroxyanthraquinone also inhibited 17beta-estradiol binding to human estrogen receptors (ERs) with K(i) values of 0.77 and 0.31microM for ERalpha and 1.5 and 0.69 microM for ERbeta. These findings indicate that hydroxyanthraquinones such as emodin are phytoestrogens with an affinity to human estrogen receptors.

PMID: 11459643 [PubMed - indexed for MEDLINE]

Method of using aloe vera as a biological vehicle (1998 patent)
(does this suggest it would multiply intensity of estrogen?)

http://www.freepatentsonline.com/5708038.html
http://www.freepatentsonline.com/5708038.pdf

Quote:

The significance of these findings, as stated above, is that if Aloe vera is administered in combination with estrogens or androgens, lower doses of the hormones can be used to achieve the same therapeutic effect, thereby eliminating or reducing any side effects associated with higher doses. Additionally, Aloe vera is nontoxic and nonirritating, even at very large doses.

J Korean Med Sci. 2010 Mar;25(3):492-5. Epub 2010 Feb 17.
Aloe-induced Toxic Hepatitis.

Yang HN, Kim DJ, Kim YM, Kim BH, Sohn KM, Choi MJ, Choi YH.
Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Korea.
Aloe has been widely used in phytomedicine. Phytomedicine describes aloe as a herb which has anti-inflammatory, anti-proliferative, anti-aging effects. In recent years several cases of aloe-induced hepatotoxicity were reported. But its pharmacokinetics and toxicity are poorly described in the literature. Here we report three cases with aloe-induced toxic hepatitis. A 57-yr-old woman, a 62-yr-old woman and a 55-yr-old woman were admitted to the hospital for acute hepatitis. They had taken aloe preparation for months. Their clinical manifestation, laboratory findings and histologic findings met diagnostic criteria (RUCAM scale) of toxic hepatitis. Upon discontinuation of the oral aloe preparations, liver enzymes returned to normal level. Aloe should be considered as a causative agent in hepatotoxicity.

PMID: 20191055 [PubMed - in process]

Laurel · 11-24-2009, 07:45 PM

Wow! I'm lovin' this!