beta-elemene and Neoplasms

Topics: Animals; Antineoplastic Agents; Chemoradiotherapy; Humans; Neoplasms; Radiation Tolerance; Sesquiterpenes

Entry of β-elemene into various phases of clinical trials advocates its significance as a premium candidate likely to gain access to mainstream medicine. Based on the insights gleaned from decades of research, it seems increasingly transparent that β-elemene has shown significant ability to modulate multiple cell signaling pathways in different cancers. We partition this multicomponent review into how β-elemene strategically modulates various signal transduction cascades. We have individually summarized regulation of tumor necrosis factor related apoptosis-inducing ligand, signal transducers and activators of transcription, transforming growth factor/SMAD, NOTCH, and mammalian target of rapamycin pathways by β-elemene. Last, we will discuss the results of clinical trials of β-elemene and how effectively we can use these findings to stratify patients who can benefit most from β-elemene.

Topics: Animals; Apoptosis; Clinical Trials as Topic; Disease Progression; Humans; Neoplasm Metastasis; Neoplasms; Sesquiterpenes; Signal Transduction

β-Elemene is a sesquiterpene compound extracted from the herb Curcuma Rhizoma and is used in traditional Chinese medicine (TCM) to treat several types of cancer, with no reported severe adverse effects. Recent studies, using in vitro and in vivo studies combined with molecular methods, have shown that β-elemene can inhibit cell proliferation, arrest the cell cycle, and induce cell apoptosis. Recent studies have identified the molecular targets of β-elemene that may have a role in cancer therapy. This review aims to discuss the anticancer potential of β-elemene through its actions on several molecular targets including kinase enzymes, transcription factors, growth factors and their receptors, and proteins. β-Elemene also regulates the expression of several key molecules that are involved in tumor angiogenesis and metastasis including vascular endothelial growth factor (VEGF), matrix metalloproteinases (MMPs), E-cadherin, N-cadherin, and vimentin. Also, β-elemene has been shown to have regulatory effects on the immune response and increases the sensitivity of cancer cells to chemoradiotherapy and has shown effects on multidrug resistance (MDR) in malignancy. Recent studies have shown that β-elemene can induce autophagy, which prevents cancer cells from undergoing apoptosis. Therefore, the molecular mechanisms for the treatment effects on cancer of the herbal extract, β-elemene, which has been used for centuries in traditional Chinese medicine, are now being studied and identified.

Topics: Animals; Antineoplastic Agents; Apoptosis; Autophagy; Cell Proliferation; Drugs, Chinese Herbal; Humans; Medicine, Chinese Traditional; Neoplasms; Plant Extracts; Sesquiterpenes

β-elemene is a noncytotoxic Class II antitumor drug extracted from the traditional Chinese medicine

Topics: Animals; Drug Delivery Systems; Humans; Liposomes; Nanoparticles; Neoplasms; Sesquiterpenes

Increasing knowledge on the hallmark characteristics of cancer and tumor pharmacology has promoted the introduction of phytochemicals, such as traditional Chinese medicine (TCM) in cancer therapy, which modulate numerous molecular targets and exert anticancer activities. β-elemene, an active and non-toxic compound isolated from the Chinese medicinal herb Rhizoma Zedoariae, has been explored as a potent anti-cancer agent against multiple cancers in extensive clinical trials and experimental research in vivo and in vitro. β-elemene exerts therapeutic potential via modulation of core hallmark capabilities of cancer by suppressing proliferative signaling, such as MAPK and PI3K/Akt/mTOR pathway, inducing cell death, up-regulating growth suppressors, deactivating invasion and metastasis and interacting replicative immortality and attenuating angiogenesis. Recent studies have significantly improved our understanding of anti-cancer activities and underlying molecular mechanisms of this Chinese medicine. This review presents these novel findings regarding the unique properties of β-elemene as an agent for cancer treatment, with an emphasis on multi-targeting biological and molecular regulation.

Topics: Antineoplastic Agents, Phytogenic; Cell Proliferation; Drug Screening Assays, Antitumor; Humans; Molecular Structure; Neoplasms; Rhizome; Sesquiterpenes; Structure-Activity Relationship

Multidrug resistance (MDR), defined as the resistance of cancer cells to compounds with diverse structures and mechanisms of actions, significantly limits the efficacy of antitumor drugs. A major mechanism that mediates MDR in cancer is the overexpression of adenosine triphosphate (ATP)-binding cassette transporters. These transporters bind to their respective substrates and catalyze their efflux from cancer cells, thereby lowering the intracellular concentrations of the substrates and thus attenuating or even abolishing their efficacy. In addition, cancer cells can become resistant to drugs via mechanisms that attenuate apoptosis and cell cycle arrest such as alterations in the p53, check point kinase, nuclear factor kappa B, and the p38 mitogen-activated protein kinase pathway. In this review, we discuss the mechanisms by which β-elemene, a compound extracted from Rhizoma zedoariae that has clinical antitumor efficacy, overcomes drug resistance in cancer.

Topics: Antineoplastic Agents; Apoptosis; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Neoplasms; Pinellia; Sesquiterpenes

Topics: Adjuvants, Immunologic; Anti-Bacterial Agents; Combined Modality Therapy; Neoplasms; Sesquiterpenes

Tumor-associated macrophages (TAMs) play a critical role in the immunosuppressive solid tumor microenvironment (TME), yet in situ engineering of TAMs for enhanced tumor immunotherapy remains a significant challenge in translational immuno-oncology. Here, we report an innovative nanodrug-delivering-drug (STNSP@ELE) strategy that leverages two-dimensional (2D) stanene-based nanosheets (STNSP) and β-Elemene (ELE), a small-molecule anticancer drug, to overcome TAM-mediated immunosuppression and improve chemo-immunotherapy. Our results demonstrate that both STNSP and ELE are capable of polarizing the tumor-supportive M2-like TAMs into a tumor-suppressive M1-like phenotype, which acts with the ELE chemotherapeutic to boost antitumor responses. In vivo mouse studies demonstrate that STNSP@ELE treatment can reprogram the immunosuppressive TME by significantly increasing the intratumoral ratio of M1/M2-like TAMs, enhancing the population of CD4

Topics: Animals; Immunotherapy; Macrophages; Melanoma; Mice; Nanoparticles; Neoplasms; Tumor Microenvironment; Tumor-Associated Macrophages

Ultrasound (US)-mediated sonodynamic therapy (SDT) has emerged as a superior modality for cancer treatment owing to the non-invasiveness and high tissue-penetrating depth. However, developing biocompatible nanomaterial-based sonosensitizers with efficient SDT capability remains challenging. Here, we employed a liquid-phase exfoliation strategy to obtain a new type of two-dimensional (2D) stanene-based nanosheets (SnNSs) with a band gap of 2.3 eV, which is narrower than those of the most extensively studied nano-sonosensitizers, allowing a more efficient US-triggered separation of electron (e

Topics: Biocompatible Materials; Combined Modality Therapy; Drug Carriers; Drug Delivery Systems; Humans; Molecular Structure; Nanomedicine; Nanoparticles; Neoplasms; Particle Size; Photothermal Therapy; Reactive Oxygen Species; Sesquiterpenes; Ultrasonic Therapy; Ultrasonic Waves

Arsenical drugs have achieved hallmark success in treating patients with acute promyelocytic leukemia, but expanding their clinical utility to solid tumors has proven difficult with the contradiction between the therapeutic efficacy and the systemic toxicity. Here, leveraging efforts from materials science, biocompatible PEGylated arsenene nanodots (AsNDs@PEG) with high monoelemental arsenic purity that can selectively and effectively treat solid tumors are synthesized. The intrinsic selective killing effect of AsNDs@PEG is closely related to high oxidative stress in tumor cells, which leads to an activated valence-change of arsenic (from less toxic As

Topics: Animals; Antineoplastic Agents; Arsenic; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Survival; DNA Damage; Drug Therapy, Combination; Humans; Infrared Rays; Mice; Mice, Nude; Nanoparticles; Neoplasms; Oxidative Stress; Photothermal Therapy; Polyethylene Glycols; Reactive Oxygen Species; Sesquiterpenes; Transplantation, Heterologous

β-Elemene is a bioactive sesquiterpene compound that exhibits a potent anti-tumor effect and is used in various clinical applications. However, little is known about its effect on the male reproductive system. The objective of this study was to investigate the in vitro actions of β-elemene on human sperm function and elucidate the underlying mechanism.. The cytotoxicity of β-elemene toward MCF-10A, MDA-MD-231, and A549 cells was evaluated with cell proliferation and colony formation assays. Additionally, human sperm were treated with different concentrations (0, 10, 20, 40, 80, 160, and 320 µM) of β-elemene in vitro. The characteristics in human sperm essential for fertilization, including vitality, motility, capacitation, acrosome reaction, responsiveness to progesterone, and intracellular calcium concentration ([Ca2+]i) were examined with a computer-assisted sperm analysis system, chlortetracycline staining, and a fluorescent Ca2+ indicator.. A comprehensive evaluation of sperm motility, especially hyperactivated motility, revealed that treatments with 40-320 μM β-elemene decreased human sperm vitality, motility (total motility, progressive motility, and curvilinear velocity), and penetrating ability in a dose-dependent manner, but were non-toxic or minimally toxic toward MCF-10A, MDA-MD-231, and A549 cells. Although 10 and 20 μM β-elemene did not affect sperm vitality and motility, these concentrations increased the spontaneous acrosome reaction and inhibited progesterone-induced sperm functions by affecting sperm [Ca2+]i.. These results suggest that β-elemene inhibits human sperm function by affecting sperm vitality and [Ca2+]i. These observations must be considered when using β-elemene to treat cancer patients who may wish to preserve their fertility.

Topics: Antineoplastic Agents; Calcium; Cell Line, Tumor; Cell Survival; Humans; Male; Neoplasms; Sesquiterpenes; Sperm Motility; Spermatozoa

Intravenously injectable emulsion of β-elemene was studied in detail. Both blank and β-elemene-loaded microemulsions were prepared using a simple water titration method. The pseudoternary phase diagram was constructed for the optimization of microemulsion. The loading capacity test, dilutability test, and especially the influence of antioxidants were conducted for further optimization of β-elemene-loaded microemulsion. Transmission electron microscope showed intact and spherical microemulsion droplets. Conductivity and viscosity measurements were used to study the phase behaviors of β-elemene-loaded microemulsions, providing convincing explanation. In vitro release study showed that β-elemene was steadily released until 12 h, which most fitted the first order.

Topics: Antineoplastic Agents, Phytogenic; Antioxidants; Drug Compounding; Drug Delivery Systems; Electric Conductivity; Emulsions; Humans; In Vitro Techniques; Neoplasms; Particle Size; Sesquiterpenes; Viscosity

To evaluate the quality of randomized controlled trials (RCTs) for Elemene injections, one ingredient of Chinese herb Curcuma wenyujin, for malignant tumors widely used in clinical practice in China.. We used a systematic sample of 127 reports of RCTs that used Elemene injections as an intervention. The quality of each report was assessed using the number of Consolidated Standards for Reporting of Trials (CONSORT) checklist items included, the frequency of allocation concealment and a 5-point quality assessment instrument (Jadad).. 69.44% of the CONSORT checklist items was included in the reports. Only 2 (1.57%) RCTs reported allocation concealment by sealed envelopes. 123 (96.85%) reports described baseline demographic and clinical characteristics of each group. But only 5 (3.94%) of 127 RCTs reported statistics analysis results of baseline data. None of the reports stated in the methods section that intention-to-treat (ITT) analysis was used, although 111 (87.40%) reports described the number of participants (denominator) in each group included in each analysis. Information regarding adverse events was reported in 83.46% of the RCTs. However the quality of reports were low as assessed by the Jadad scale.. The methodological quality of RCTs of Elemene injection against malignant tumors was low. Therefore, the effect of Elemene injection being used in clinical settings needs to be confirmed by further RCTs. Meanwhile, there is a need to supervise and urge researchers in China to conform to Good Clinical Practice (GCP) and CONSORT guidelines when reporting.

Topics: Antineoplastic Agents; Curcuma; Databases, Factual; Drugs, Chinese Herbal; Humans; Neoplasms; Randomized Controlled Trials as Topic; Research Design; Sesquiterpenes