beta-escin and Neoplasms

Although modern medicine is advancing at an unprecedented rate, basic challenges in cancer treatment and drug resistance remain. Exploiting natural-product-based drugs is a strategy that has been proven over time to provide diverse and efficient approaches in patient care during treatment and post-treatment periods of various diseases, including cancer. Escin-a plant-derived triterpenoid saponin-is one example of natural products with a broad therapeutic scope. Initially, escin was proven to manifest potent anti-inflammatory and anti-oedematous effects. However, in the last two decades, other novel activities of escin relevant to cancer treatment have been reported. Recent studies demonstrated escin's efficacy in compositions with other approved drugs to accomplish synergy and increased bioavailability to broaden their apoptotic, anti-metastasis, and anti-angiogenetic effects. Here, we comprehensively discuss and present an overview of escin's chemistry and bioavailability, and highlight its biological activities against various cancer types. We conclude the review by presenting possible future directions of research involving escin for medical and pharmaceutical applications as well as for basic research.

Topics: Escin; Humans; Neoplasms; Plant Extracts

Escin is a mixture of triterpenoid saponins extracted from the horse chestnut tree, Aesculus hippocastanum. Its potent anti-inflammatory and anti-odematous properties makes it a choice of therapy against chronic venous insufficiency and odema. More recently, escin is being actively investigated for its potential activity against diverse cancers. It exhibits anti-cancer effects in many cancer cell models including lung adenocarcinoma, hepatocellular carcinoma and leukemia. Escin also attenuates tumor growth and metastases in various in vivo models. Importantly, escin augments the effects of existing chemotherapeutic drugs, thereby supporting the role of escin as an adjunct or alternative anti-cancer therapy. The beneficial effects of escin can be attributed to its inhibition of proliferation and induction of cell cycle arrest. By regulating transcription factors/growth factors mediated oncogenic pathways, escin also potentially mitigates chronic inflammatory processes that are linked to cancer survival and resistance. This review provides a comprehensive overview of the current knowledge of escin and its potential as an anti-cancer therapy through its anti-proliferative, pro-apoptotic, and anti-inflammatory effects.

Topics: Animals; Antineoplastic Agents; Apoptosis; Biomarkers, Tumor; Cell Cycle Checkpoints; Cell Proliferation; Clinical Studies as Topic; Drug Evaluation, Preclinical; Escin; Humans; Molecular Targeted Therapy; Neoplasms

Aescin, a natural mixture of triterpene saponins, has been reported to exert anticancer effect. Recent studies show that aescin increases intracellular reactive oxygen species (ROS) levels. However, whether the increased ROS play a role in the anticancer action of aescin remains to be explored. In this study, we demonstrated that aescin (20-80 μg/mL) dose-dependently induced apoptosis and activated mammalian target of rapamycin (mTOR)-independent autophagy in human hepatocellular carcinoma HepG2 cells and colon carcinoma HCT 116 cells. The activation of autophagy favored cancer cell survival in response to aescin, as suppression of autophagy with ATG5 siRNAs or 3-methyladenine (3-MA), a selective inhibitor of autophagy, promoted aescin-induced apoptosis in vitro, and significantly enhanced the anticancer effect of aescin in vivo. Meanwhile, aescin dose-dependently elevated intracellular ROS levels and activated Ataxia-telangiectasia mutated kinase/AMP-activated protein kinase/UNC-51-like kinase-1 (ATM/AMPK/ULK1) pathway. The ROS and ATM/AMPK/ULK1 pathway were upstream modulators of the aescin-induced autophagy, as N-acetyl-L-cysteine (NAC) or ATM kinase inhibitor (KU-55933) remarkably suppressed aescin-induced autophagy and consequently promoted aescin-induced apoptosis, whereas overexpression of ATG5 partly attenuated NAC-induced enhancement in aescin-induced apoptosis. In conclusion, this study provides new insights into the roles of aescin-mediated oxidative stress and autophagy in cancer cell survival. Our results suggest that combined administration of the antioxidants or autophagic inhibitors with aescin might be a potential strategy to enhance the anticancer effect of aescin.

Topics: AMP-Activated Protein Kinases; Animals; Antineoplastic Agents; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Autophagy; Autophagy-Related Protein-1 Homolog; Cell Line, Tumor; Escin; Female; Humans; Intracellular Signaling Peptides and Proteins; Mice, Nude; Neoplasms; Reactive Oxygen Species; Signal Transduction

This study examined the antiproliferative effects of β-escin (E) in cancer cells. The study showed that E inhibited cancer cells growth in a dose-dependent manner. The flow cytometric analysis revealed an escin-induced increase in the sub-G1 DNA content, which is considered to be a marker of apoptosis. Apoptosis was also confirmed by annexin V staining and DNA fragmentation assay. These effects were associated with increased generation of reactive oxygen species (ROS), caspase-3 activation and decreased mitochondrial membrane potential (MMP). Moreover, escin decreased mitochondrial protein content and mitochondrial fluorescence intensity as well as caused depletion of glutathione (GSH). However, activity of glutathione peroxidase (GPx) and glutathione reductase (GR) was not significantly changed in escin-treated cells. In conclusion, our results demonstrated that E has apoptotic effects in human cancer cells through the mechanisms involving mitochondrial perturbation. Although the exact mechanism needs to be investigated further, it can be concluded that E may be a useful candidate agent for cancer treatment.

Topics: Apoptosis; Caspase 3; Cell Line, Tumor; Cell Proliferation; DNA Fragmentation; Dose-Response Relationship, Drug; Enzyme Activation; Escin; Glutathione; Glutathione Peroxidase; Glutathione Reductase; Humans; In Vitro Techniques; Membrane Potential, Mitochondrial; Neoplasms; Reactive Oxygen Species

Topics: Aesculus; Cell Membrane; Escin; Humans; Ions; Neoplasms; Permeability; Potassium; Sodium