
 aloe vera gel is a colorless substance obtained from the parenchymatous cells in fresh leaves of aloe vera ( l ) burm .
native to north africa , aloe has been introduced and is being cultivated in the warmer areas of the world . aloe vera gel , rich in polysaccharides ( pectins , hemicelluloses , glucomannan , acemannan , and other mannose derivatives ) should not be confused with the drug  aloe   dried juice of aloe vera leaves , bitter yellow exudate containing anthracene glycosides , mainly of the aloe - emodin anthrone 10-c - glucoside type [ 1 , 2 ] . 

consumed as a beverage it was not toxic in vivo for mice . on the contrary , aloe latex and its hydroxyanthrone derivatives ( aloin , aloe - emodin etc . )
have strong laxative properties and their longer use requires medical supervision . traditionally , aloe gel was widely used for the treatment of minor wounds , inflammatory skin disorders , and thermal and radiation burns . in vitro ,
aloe gel suppressed bacteria - induced pro - inflammatory [ tumor necrosis factor  ( tnf- ) and interleukin 1 ( il-1 ) ] cytokines and matrix metalloproteinase 9 ( mmp-9 ) production in human mononuclear leukocytes [ 4 , 5 ] . 
 in vivo , polysaccharides derived from aloe vera gel , injected into mice , potently stimulated migration of macrophages to the peritoneal cavity . in human , oral aloe vera gel was used by patients with inflammatory bowel disease , osteoarthritis , and other inflammatory conditions .
oral and topical administration of aloe vera gel diminished inflammation and eased joint immobility and pain [ 811 ] . in ophthalmology
, aloe vera extracts may be used in eye drops to treat inflammations and other cornea ailments . besides its anti - inflammatory activity
, aloe vera gel has antimicrobial properties and in vivo exerts a protective effect on polymicrobial sepsis in mice [ 1317 ] .
anthraquinones , compounds present in the outer part of aloe leaves and in their succus or extract , have been shown to have direct anti - cancer activity in different kinds of human cancer cell lines . moreover , aloe - emodin , a hydroxyanthraquinone from aloe vera , can act as an anti - angiogenic agent .
some data suggest that the inner part of aloe vera leaves , aloe vera gel and their polysaccharide components also have tumor growth modulatory properties , probably connected with their immunomodulatory activity [ 20 , 21 ] . in our previous paper
we reported the inhibitory effect of aloe barbadensis fresh leaves aqueous extract ( herbal drug biostymina ) on tumor - induced cutaneous angiogenesis in mice .
the aim of the present study was to evaluate in balb / c mice the in vivo influence of commercial aloe vera gel product ( aloe vera drinking gel ) on the syngeneic l-1 sarcoma tumor growth and its vascularization : a ) early cutaneous neovascular response , tumor - induced angiogenesis ( tia test ) , and b ) tumor hemoglobin content measured 14 days after l-1 sarcoma cell grafting .

 drug . tru - alo 99% aloe vera drinking gel ( aloe barbadensis miller folium succus ) , aloin content < 40 ppm ; produced by hi tech aloe vera pty ltd , bundaberg , australia
the study was performed on 59 female inbred balb / c mice 6 - 8 weeks old , weighing about 20 g , delivered from the polish academy of sciences breeding colony .
for all performed experiments animals were handled according to the polish law on the protection of animals and nih ( national institutes of health ) standards .
mice were housed 4 - 5 per cage and maintained under conventional conditions ( room temperature 22.5 - 23.0c , relative humidity 50 - 70% , 12 h day / night cycle ) with free access to standard rodent diet and water .
ketamina 10% , biowet , pulawy , poland ) ; xylazine 10 mg / kg ( prep .
sedazin , biowet , pulawy , poland ) ; 3.6% chloral hydrate 0.1 ml per 10 g of body mass ( sigma aldrich , usa ) ; morbital ( biowet pulawy , poland ) . 

evaluation of sarcoma l-1 growth and angiogenic activity was performed as previously described [ 23 , 24 ] .
l-1 sarcoma cells were delivered from warsaw oncology center collection , passaged twice in vivo and grafted subcutaneously ( for evaluation of tumor growth and its hemoglobin ( hb ) content ) or intradermally ( for evaluation of their angiogenic activity ) to syngeneic balb / c mice . 

briefly , sarcoma l-1 cells from in vitro stock were grafted ( 106/0.1 ml ) subcutaneously into the subscapular region of balb / c mice .
after 14 days the tumors were excised , cut to smaller pieces , rubbed through the sieve and suspended in 5 ml of phosphate buffered saline ( pbs ) .
after sedimentation , the supernatant was collected and centrifuged for 10 min at 1500 rpm . obtained sarcoma cells were washed once with pbs for 10 min , then centrifuged at 1500 rpm , and resuspended in parker medium in concentration of 4  10/ml or 10/ml .
multiple 0.05 ml samples of 200 thousand sarcoma cells were injected intradermally into partly shaved , narcotized balb / c mice ( at least 2 - 4 mice per group ) . in order to facilitate the localization of cell injection sites , the suspension
mice obtained aloe vera gel ( 150 l for one mouse daily ) in drinking water for 3 days . after 72 hours mice were sacrificed with a lethal dose of morbital .
all newly formed blood vessels were identified and counted in the dissection microscope , on the inner skin surface , at magnification of 6 , in 1/3 of the central area of the microscopic field .
identification was based on the fact that new blood vessels are thin , directed to the point of cell injection , with ramifications , and some of them are tortuous ( fig .
neovascular reaction 3 days after the intradermal injection of tumor cells 0.1 ml samples of 1 million sarcoma cells were grafted subcutaneously into the sub - scapular region of balb / c mice . on the day of cell grafting and on the following 13 days mice obtained 150 l of aloe vera gel in drinking water , or water as a control .
tumors were removed , weighed and measured with an electronic caliper ( the fowler ultra - cal mark iii caliper ) . 

briefly , tumors were homogenized in pbs using an ultrasonic sonificator ( virsonic , usa ) , then centrifuged for 20 min at 4000  g. 20 l of the supernatant was added to 5 ml of drabkin reagent .
the absorbance was read in a spectrophotometric reader elx800 ( biotek instruments , usa ) at 570 nm .
the reader for the hb measurement was calibrated with hemoglobin standard solutions ( sigma ) .
multiple 0.05 ml samples of 200 thousand sarcoma cells were injected intradermally into partly shaved , narcotized balb / c mice ( at least 2 - 4 mice per group ) . in order to facilitate the localization of cell injection sites , the suspension
mice obtained aloe vera gel ( 150 l for one mouse daily ) in drinking water for 3 days . after 72 hours mice were sacrificed with a lethal dose of morbital .
all newly formed blood vessels were identified and counted in the dissection microscope , on the inner skin surface , at magnification of 6 , in 1/3 of the central area of the microscopic field .
identification was based on the fact that new blood vessels are thin , directed to the point of cell injection , with ramifications , and some of them are tortuous ( fig .
0.1 ml samples of 1 million sarcoma cells were grafted subcutaneously into the sub - scapular region of balb / c mice . on the day of cell grafting and on the following 13 days mice obtained 150 l of aloe vera gel in drinking water , or water as a control .
tumors were removed , weighed and measured with an electronic caliper ( the fowler ultra - cal mark iii caliper ) . 

briefly , tumors were homogenized in pbs using an ultrasonic sonificator ( virsonic , usa ) , then centrifuged for 20 min at 4000  g. 20 l of the supernatant was added to 5 ml of drabkin reagent .
the absorbance was read in a spectrophotometric reader elx800 ( biotek instruments , usa ) at 570 nm .
the reader for the hb measurement was calibrated with hemoglobin standard solutions ( sigma ) .
two - tailed p value was lower than 0.0001 ( t = = 4.467 ; df = 70 ) .
hence , the mean number of newly formed blood vessels in the experimental , aloe - fed group of mice was highly significantly lower than in the corresponding controls ( fig .
2 ) mean number of newly - formed blood vessels counted 3 days after the intradermal injection of sarcoma l-1 cells the difference between the groups of control and aloefed mice ( 150 l daily dose for 14 days ) with respect to the 14 days tumor volume was on the border of statistical significance ( fig .
no difference was observed in hemoglobin content between control and experimental tumors ( 21.3 3.1 vs. 24.1 3.6 g / mg , respectively ) . the effect of feeding mice with aloe vera drinking gel for 14 days after l-1 sarcoma subcutaneous grafting on the tumor volume ( difference on the border of statistical significance )
it was shown by other authors that some aloe vera active components slow down the experimental tumor growth . three anthraquinones ( aloesin
, aloe - emodin and barbaloin ) extracted from aloe vera leaves may exert their chemo - preventive effect through modulating antioxidant and detoxification enzyme activity levels .
aloe - emodin induces cell death through s - phase arrest and apoptosis in the dose- and time - dependent manner .
other researchers describe the anti - tumour effect of specific derivatives of the aloe vera plant .
di(2-ethylhexyl)phthalate isolated from aloe vera linne may have anti - leukemic and anti - mutagenic properties .
the anti - tumor effect was also documented for the aloe vera leaf pulp extract and the main lectin ( aloctin i ) present in it , in the ehrlich ascites tumor model .
acemannan , the compound of the extract from the parenchyma of aloe vera / aloe barbadensis , stimulates the synthesis of monokines and recruitment of immune cells and , by this mechanism , necrosis and regression of murine sarcoma .
the results of these studies suggest that this effect could be due to its immunomodulatory activity .
acemannan has been approved by the fda - us as a potent immunomodulating and anti - viral agent .
it was approved as an aid in the treatment of canine and feline fibrosarcoma . however , the critical condition for the tumor to effectively metastasize is formation of the new vessels prompted by a group of cancer cells derived from the primary , transported by the blood circulation and grafted in  permissible  tissue environment .
this  permissiveness  is conditioned by the agents released by the tumor cells that drive recipient tissue to facilitate new vessel growth in it .
we have been able to show that aloe vera drinking gel slows down an early phase of new vessel formation and their in - growth in hosting tissue .
however , aloe vera drinking gel has not caused the necrotical effect on the tumor volume and it has not influenced the vascularity of the mature tumor ( as indicated by the lack of differences in hemoglobin content of tumors between groups ) .
it may suggest that its effect is exerted only on the newly forming vessels during micrometastasis implantation .
few cytotoxic and targeted drugs have been proven effective in adjuvant systemic therapies after most of the tumor was removed by surgery or radiotherapy .
the presence of micrometastases at the time of primary therapy is emphasized as the cause of failure of loco regional therapies .
the effective chemoprevention should be directed at the micrometastasis priming mechanism , that is among most important angiogenesis .
aloe vera drinking gel , having a low profile of side effects , may be a good candidate for supplemental therapy . however , aloe vera is also known for its beneficial wound healing impact that might be partly attributed to its compound , -sitosterol , pro - angiogenic properties .
it was shown that in the presence of heparin , beta - sitosterol stimulated neovascularization in the mouse matrigen plug assay , and the motility of human umbilical vein endothelial cells in an in vitro wound migration assay .
therefore , further detailed studies on the specific compounds contribution of the antiangiogenic effect and its mechanism are warranted .
performed a randomized study of chemotherapy versus chemotherapy plus aloe arborescens , in 240 patients with lung , colorectal , gastric and pancreatic metastatic cancers .
aloe arborescens was given orally at a dose of 10 ml thrice daily of a mixture consisting of 300 g of aloe fresh leaves in 500 g of honey plus 40 ml of 40% alcohol , every day without interruption , either during or after chemotherapy , until the progression of disease , starting 6 days prior to the onset of chemotherapy .
the results of this study suggest that aloe may be successfully associated with chemotherapy to increase the tumor regression rate and survival time .
 aloe vera ( aloe arborescens , aloe barbadensis ) is a medicinal plant belonging to the liliaceae family . 
 aloe vera gel prepared from the inner part of aloe leaves is increasingly consumed as a beverage dietary supplement . 
 some data suggest its tumor growth modulatory properties . 
 the aim of the present study was to evaluate in balb / c mice the in vivo influence of orally administered aloe vera drinking gel on the syngeneic l-1 sarcoma tumor growth and its vascularization : early cutaneous neovascular response , tumor - induced angiogenesis ( tia test read after 3 days ) , and tumor hemoglobin content measured 14 days after l-1 sarcoma cell grafting.feeding mice for 3 days after tumor cell grafting with 150 l daily dose of aloe vera gel significantly diminished the number of newly - formed blood vessels in comparison to the controls . the difference between the groups of control and aloe - fed mice ( 150 l daily dose for 14 days ) with respect to the 14 days tumor volume was on the border of statistical significance . 
 no difference was observed in tumor hemoglobin content . 