Aloe Vera (Aloe vera) and Cancer (anticancer research): evidence and sources

Background/Objectives : Cancer, a multifactorial disease with uncontrolled cell growth, oxidative stress, inflammation, genomic instability, and molecular signaling pathways, is a global health concern, leading to the ~20 million newly diagnosed cases annually. Although conventional therapy has been shown to enhance the survival rates of cancer patients, its clinical efficacy is limited by certain side effects that occur as a result of treatment, thus necessitating the exploration of plant-derived bioactive compounds for their potential as safer and alternative supportive therapeutic agents. Aloe vera , known as the plant of immortality, comprises phytochemicals, such as anthraquinones (aloe-emodin, emodin, and aloin), polysaccharides (acemannan), flavonoids, and phenolic acids, which contribute to the pharmacological effect of the compound. Methods : This review summarizes the anticancer potential of Aloe vera , and the data were retrieved from databases, such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Wiley Online Library, during the time period of 2015 to 2025. Results : The literature revealed that Aloe vera and its bioactive compounds have dose-dependent cytotoxic and anti-proliferative properties against hepatocellular, cervical, colorectal, lung, breast, prostate, and hematological cancers, which are significantly mediated by apoptosis and pyroptosis induction, reactive oxygen species (ROS) production, mitochondrial dysfunction, inhibition of angiogenesis and metastasis, and the modulation of key signaling pathways, particularly PI3K/Akt, MAPK, NF-кB, p53, and Wnt/β-catenin. Furthermore, anthraquinones, including Aloe-emodin, demonstrate potent anticancer effects at micro-molar doses, and polysaccharides increase immune reactions and provide tumor immunity. Conclusions : Conclusively, Aloe vera is a promising multi-target natural compound, particularly efficient in the treatment of cancer. However, despite significant therapeutic potential, more research on pharmacokinetics, standard dose, and controlled clinical trials of Aloe vera is required to validate clinical applicability.

Objective: Aloe-emodin (AE) is an anthraquinone compound extracted from the rhizome of the natural plant rhubarb. Initially, it was shown that AE exerts an anti-inflammatory effect. Further studies revealed its antitumor activity against various types of cancer. However, the mechanisms underlying these properties remain unclear. Based on network pharmacology and molecular docking, this study investigated the molecular mechanism of AE in the treatment of hepatocellular carcinoma (HCC), and evaluated its therapeutic effect through in vitro experiments. Methods: CTD, Pharmmapper, SuperPred and TargetNet were the databases to obtain potential drug-related targets. DisGenet, GeneCards, OMIM and TTD were used to identify potential disease-related targets. Intersection genes for drugs and diseases were obtained through the Venn diagram. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of intersecting genes were conducted by the website of Bioinformatics. Intersection genes were introduced into STRING to construct a protein-protein interaction network, while the Cytoscape3.9.1 software was used to visualize and analyze the core targets. AutoDock4.2.6 was utilized to achieve molecular docking between drug and core targets. In vitro experiments investigated the therapeutic effects and related mechanisms of AE. Results: 63 overlapped genes were obtained and GO analysis generated 3,646 entries by these 63 intersecting genes. KEGG analysis mainly involved apoptosis, proteoglycans in cancer, TNF signaling pathway, TP53 signaling pathway, PI3K-AKT signaling pathway, etc. AKT1, EGFR, ESR1, TP53, and SRC have been identified as core targets because the binding energies of them between aloe-emodin were less than -5 kcal/Mol.The mRNA and protein expression, prognosis, mutation status, and immune infiltration related to core targets were further revealed. The involvement of AKT1 and EGFR, as well as the key target of the PI3K-AKT signaling pathway, indicated the importance of this signaling pathway in the treatment of HCC using AE. The results of the Cell Counting Kit-8 assay and flow analysis demonstrated the therapeutic effect of AE. The downregulation of EGFR, PI3KR1, AKT1, and BCL2 in mRNA expression and PI3KR1, AKT,p-AKT in protein expression confirmed our hypothesis. Conclusion: Based on network pharmacology and molecular docking, our study initially showed that AE exerted a therapeutic effect on HCC by modulating multiple signaling pathways. Various analyses confirmed the antiproliferative activity and pro-apoptotic effect of AE on HCC through the PI3K-AKT signaling pathway. This study revealed the therapeutic mechanism of AE in the treatment of HCC through a novel approach, providing a theoretical basis for the clinical application of AE.

Aims Non-small-cell lung cancer (NSCLC) is the most frequent type of lung cancer with a high mortality rate. Glycosylation of phenolic compounds may increase water-solubility and pharmacological activities and reduce the toxicity of aglycones. This study aimed to evaluate and compare the anticancer effect of aloe emodin 3-O-glucoside (AE3G) and its aglycone, aloe emodin (AE), against NSCLC. Main method A human adenocarcinoma cell line (A549) and other human non-small cell lung carcinoma cell lines (NCI-H460 cells and NCI-H1299 cells) and BALB/c nu/nu xenograft mice harbouring A549 cells were used as the NSCLC models. Inhibition of cell migration, disruption of mitochondrial membrane potential (MMP), DNA fragmentation, and expression levels of apoptotic proteins were measured by western blot, wound healing assay, JC-1 staining, or TUNEL staining. Histopathological changes in tumour tissues were observed by H&E and TUNEL staining. Results With no significant cytotoxicity against noncancerous cells (Vero cells), AE3G (5-50 μM) significantly and more effectively inhibited the growth, attachment, migration, Bcl-2 expression, and activation of MEK/ERK and Akt signalling proteins and induced cytochrome c release and Bax expression in A549 cells than AE. AE3G also significantly decreased the growth of other NSCLC cells, NCI-H460 cells and NCI-H1299 cells. AE3G suppressed the mRNA expression of matrix metalloproteinases, MMP2 and MMP9, and augmented the collapse of the mitochondrial MMP, cleavage of caspases (caspase 9, 8, and 3) and PARP, and DNA fragmentation. Intraperitoneal injection of AE3G (13 and 26 mg/kg/day) reduced the tumour volume and weight and induced apoptotic cell death in tumour tissues of xenograft NSCLC mice. Significance The present study demonstrated that AE3G significantly and more effectively diminished human NSCLC cell growth and migration by triggering mitochondria-dependent intrinsic apoptosis than AE, providing AE3G as a new potent candidate to prevent or treat human NSCLC.

Glioblastoma multiforme (GBM) is the most frequent primary malignant brain tumour prevalent in humans, that exhibits aggressive cell proliferation and rapid invasion of normal brain tissue. Despite aggressive therapeutic approaches consisting of maximum safe surgical resection followed by radio-chemotherapy with temozolomide (TMZ), more than 95% of GBM patients die within 5 years after diagnosis. In most cases, the therapy is not able to counteract the growth and invasiveness of the tumour, which relapses after an interval of time that varies from patient to patient. An increasing number of evidence indicates that natural substances exhibited effective anti-tumour functions and might be successfully used in the treatment of GBM. This review summarizes some natural substances: lactoferrin, hispolon, aloe-emodin and tea tree oil; all these show a growth inhibition and synergistic effect when together with TMZ, (the most commonly used alkylating drug for the treatment of glioblastoma) were administered to U87MG glioblastoma cell line in vitro and in murine animal model. U87MG cell growth was monitored by daily cell count after treatments with the substances mentioned above and growth analysis showed that all drugs significantly decrease proliferation of U87MG in a time- and dose-dependent manner. FACS analysis demonstrates a block of cell cycle in S, G2/M or G0/G1 phases. These substances mediate multiple processes including apoptosis by releasing the inducing factor: PARP. Natural compounds, in combination with conventional chemotherapy TMZ, are a powerful approach to improve the effectiveness of brain cancer treatment.

Background Oral and pharyngeal cancer is the most common malignant human cancers. Chemotherapy is an effective approach for anti-oral cancer therapy, while the drug tolerance and resistance remain a problem for oral cancer patients. Aloe-emodin, rhein and physcion are classified as anthraquinones, which are the main pharmacodynamic ingredients of Rheum undulatum L.. This study was undertaken to investigate whether aloe-emodin, rhein and physcion show inhibiting growth and inducing apoptosis in oral squamous cell carcinoma SCC15 cells. We found that aloe-emodin show inhibiting growth and inducing apoptosis in oral squamous cell carcinoma SCC15 cells, we also investigated the underlying mechanisms of apoptosis induced by aloe-emodin. Methods Thiazolyl blue tetrazolium bromide (MTT) test was used to detect cell proliferation. Cell apoptosis was detected by flow cytometry. We also used western blot analysis to detect the potential mechanisms of apoptosis. Results Aloe-emodin, rhein and physcion inhibit the proliferation of SCC15 cells and the order of inhibition level are aloe-emodin > Rhein > Physcion, the half maximal inhibitory concentrations (IC 50 ) value of aloe-emodin was 60.90 μM at 48 h of treatment. Aloe-emodin treatment resulted in a time- and dose-dependent decrease in cell viability and increased the apoptotic cell ratio. The results of western blotting showed the expression levels of caspase-9 and caspase-3 proteins increased following aloe-emodin treatment. Conclusions Our results revealed that aloe-emodin treatment could inhibit cell viability of SCC15 cells and the potential mechanism of inhibition might be through the induction of apoptosis by regulation of the expression levels of caspase-9 and caspase-3. This indicates that aloe-emodin may be a good agent for anti-oral cancer drug exploring.

The purpose of this study was to investigate the anticancer effect of aloe-emodin, an anthraquinone compound present in the leaves of Aloe vera, on two distinct human gastric carcinoma cell lines, AGS and NCI-N87. We demonstrate that aloe-emodin induced cell death in a dose- and time-dependent manner. Noteworthy is that the AGS cells were generally more sensitive than the NCI-N87 cells. Aloe-emodin caused the release of apoptosis-inducing factor and cytochrome c from mitochondria, followed by the activation of caspase-3, leading to nuclear shrinkage and apoptosis. In addition, exposure to aloe-emodin suppressed the casein kinase II activity in a time-dependent manner and was accompanied by a reduced phosphorylation of Bid, a downstream substrate of casein kinase II and a pro-apoptotic molecule. These preclinical studies suggest that aloe-emodin represents a suitable and novel chemotherapeutic drug candidate for the treatment of human gastric carcinoma.