Rhizoma Zedoariae Research Articles

Rhizoma Zedoariae Inhibits G-CSF-Induced MDSCs-like Differentiation of THP-1 Cells

Objective: Rhizoma Zedoariae is widely used in the treatment of solid tumors in China, but there has been no deep research on its role in the formation of timmunosuppressive environments mediated by myeloid-derived suppressor cells (MDSCs) in breast cancer. This research aims to investigate the effect of Rhizoma Zedoariae extract and its active compounds curcumin and germacrone on MDSCs-like differentiation by a novel Granulocyte colony-stimulating factor (G-CSF) induced THP-1 cell model. Methods: THP-1 cells were treated with Rhizoma Zedoariae extract and its active compounds (curcumin, germacrone, curcumol, curcumenol, and curdione) at different concentrations (0.01, 0.1, 0.3, 1, 10, 30, 100, and 300 μg/mL), followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to detect the changes of cell viability in THP-1. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed to quantify the mRNA expression levels of transforming growth factor-β (TGF-β), Interleukin-10 (IL-10), Interleukin-6 (IL-6), Janus kinase 1 (JAK1), nuclear factor kappa-B (NF-κB), signal transducer and activator of transcription 3 (STAT3) and arginase-1 (ARG-1), to detected the differentiation of THP-1 into MDSCs-like cells. Results: G-CSF can induce the cell viability and MDSCs-like differentiation of THP-1 cells. Rhizoma Zedoariae extract (0.1, 1, 10, 30, 100, 300 μg/mL), germacrone (0.1, 1, 10, 30, 100, 300 μg/mL) and curcumin (0.01, 0.1, 1, 10, 30, 100 μg/mL) exerted obvious inhibitory effects (>70%) on THP-1 cell viability. G-CSF increased the ARG-1 and IL-10 mRNA levels. Rhizoma Zedoariae extract in 100 μg/mL decreased the ARG-1 and IL-10 mRNA levels. Furthermore, Rhizoma Zedoariae extract in 300 μg/mL also significantly decreased the mRNA expressions of JAK1 and STAT3 (p < 0.001). Conclusion: Rhizoma Zedoariae extract maybe inhibit G-CSF-induced MDSCs-like differentiation of THP-1 through the STAT3 pathway. The active compound that exerts this effect may be germacrone and curcumin.

Combinative effects of β-elemene and propranolol on the proliferation, migration, and angiogenesis of hemangioma.

Hemangioma (HA) is one of the most common benign vascular tumors among children. Propranolol is used as the first-line treatment for hemangioma and is a non-selective blocker of the β-adrenergic receptor. β-elemene is a compound extracted from Rhizoma zedoariae and has been approved for the treatment of tumors in clinical practice. However, the combinatorial effects of β-elemene and propranolol in the treatment of HA remains unclear. This study explored the combinative effects and mechanisms of β-elemene and propranolol using hemangioma-derived endothelial cells (HemECs). Cytotoxic assays showed that the combinatorial treatment of β-elemene and propranolol did not increase the cytotoxic effects of HemECs. Furthermore, functional analysis showed that the combinatorial treatment with β-elemene and propranolol significantly inhibited the proliferation, migration, and tube formation of the HemECs compared to the single treatment regimens. Mechanistic analysis showed that combinative treatment with β-elemene and propranolol synergistically down-regulated the hypoxia-inducible factor-1 alpha/vascular endothelial growth factor-A (HIF-1-α/VEGFA) signaling pathway. Additionally, in a xenograft tumor model, angiogenesis in the combinatorial treatment group was significantly lower than in the control, propranolol, and β-elemene treatment alone groups. Our results suggest that β-elemene combined with propranolol can significantly inhibit the proliferation, migration, and tube formation of HemECs via synergistically down-regulating the HIF-1-α/VEGFA signaling pathway without increasing any cytotoxic side effects.

The Chemopreventive Role of β-Elemene in Cholangiocarcinoma by Restoring PCDH9 Expression.

Backgroundβ-Elemene, an effective anticancer component isolated from the Chinese herbal medicine Rhizoma Zedoariae, has been proved to have therapeutic potential against multiple cancers by extensive clinical trials and experimental research. However, its preventive role in cholangiocarcinoma (CCA) and the mechanisms of action of β-elemene on CCA need to be further investigated.MethodsA thioacetamide (TAA)-induced pre-CCA animal model was well-established, and a low dosage of β-elemene was intragastrically (i.g.) administered for 6 months. Livers were harvested and examined histologically by a deep-learning convolutional neural network (CNN). cDNA array was used to analyze the genetic changes of CCA cells following β-elemene treatment. Immunohistochemical methods were applied to detect β-elemene-targeted protein PCDH9 in CCA specimens, and its predictive role was analyzed. β-Elemene treatment at the cellular or animal level was performed to test the effect of this traditional Chinese medicine on CCA cells.ResultsIn the rat model of pre-CCA, the ratio of cholangiolar proliferation lesions was 0.98% ± 0.72% in the control group, significantly higher than that of the β-elemene (0. 47% ± 0.30%) groups (p = 0.0471). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the top 10 pathways affected by β-elemene treatment were associated with energy metabolism, and one was associated with the cell cycle. β-Elemene inactivated a number of oncogenes and restored the expression of multiple tumor suppressors. PCDH9 is a target of β-elemene and displays an important role in predicting tumor recurrence in CCA patients.ConclusionsThese findings proved that long-term use of β-elemene has the potential to interrupt the progression of CCA and improve the life quality of rats. Moreover, β-elemene exerted its anticancer potential partially by restoring the expression of PCDH9.

β-elemene affects angiogenesis of infantile hemangioma by regulating angiotensin-converting enzyme 2 and hypoxia-inducible factor-1 alpha.

Infantile hemangioma (IH) is the most common benign vascular tumor resulting from the hyper-proliferation of vascular endothelial cells. In treatment of various tumors including IH, β-elemene, a compound extracted from Rhizoma zedoariae, has been reported to have anti-tumor effect. However, the underlying mechanisms of β-elemene in hemangioma have remained uninvestigated. In this presented study, functional analysis showed that low concentrations of β-elemene promoted the proliferation, migration and tube formation of human hemangioma endothelial cells (HemECs), while high concentrations of β-elemene produced inhibitory effects. Further, we also found that angiotensin-converting enzyme 2 (ACE2) expression was down-regulated at both mRNA and protein levels, while hypoxia-inducible factor-1 alpha (HIF-1-α) was up-regulated in infantile hemangiomas tissues and HemECs at both mRNA and protein levels. This result suggested that ACE2 and HIF-1-α play roles in IH. ACE2 expression was down-regulated with the treatment of β-elemene at different dosage point. Interestingly, the expression of Vascularendothelialgrowthfactor-A (VEGFA) increased with treatment of low concentrations of β-elemene in HemECs, in contrary, the expression of VEGFA expression decreased with treatment of high concentrations of β-elemene. Moreover, if the concentration of β-elemene reached 40μg/ml or higher, the expression of HIF-1-α decreased. Taken together, our data indicated that the different effects of β-elemene on the proliferation, migration and angiogenesis of hemangioma at different concentrations: The ACE2 signaling pathway dominates with treatment of low concentrations of β-elemene, stimulating the expression of downstream VEGFA to promote the angiogenesis of hemangioma; under the condition of high concentrations of β-elemene, the HIF-1-α signaling pathway inhibits the expression of VEGFA and further inhibits the angiogenesis of hemangioma.

Preparation of galactosylated curcumol liposomes

AbstractCurcumol (Cur), which is the primary active anti‐liver cancer component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in galactosylated liposomes to enhance its liver‐targeting efficacy. In this study, we optimized the preparation methods, prescription, and process of galactosylated curcumol liposomes (Gal‐Cur‐L). The experimental results showed that the encapsulation efficiency, particle diameter, and stability coefficient of Gal‐Cur‐L obtained by the two‐step emulsification method were improved compared with those of it obtained by other methods. Single‐factor investigation showed that two factors, pH and the amount of triolein, contribute at least partly to the encapsulation efficiency and particle diameter of Gal‐Cur‐L. The best prescription and process were obtained through orthogonal test: the ratio of lecithin to cholesterol was 2:1, the ratio of drug to lipid was 1:2, and the amount of ether and Twain‐80 were 4 ml and 1.6 g/L, respectively, 15 min for ultrasonic time, 100 W for ultrasonic power, and 20 min for homogeneous time. Using the best method, prescription, and process mentioned earlier, the basic test results of Gal‐Cur‐L were obtained, which demonstrated that our methods, prescription, and process of Gal‐Cur‐L were applicable. The encouraging results of this study provided references for the research of liver‐targeting reagents of curcumol.

β-elemene enhances cisplatin-induced apoptosis in bladder cancer cells through the ROS-AMPK signaling pathway.

Cisplatin-based chemotherapy is the standard regimen for patients with bladder cancer, but its effectiveness is limited by high toxicity and the development of drug resistance. β-elemene (β-ELE), a compound extracted from Rhizoma zedoariae, has antitumor activity in various malignancies and exhibits low toxicity. However, the effects and specific mechanism of β-ELE in bladder cancer remain unclear. The present study aimed to investigate the antitumor activity and possible mechanisms of β-ELE alone and in combination with cisplatin in bladder cancer cells. Cell viability was determined using Cell Counting Kit-8. Cell cycle and reactive oxygen species (ROS) analyses were performed by flow cytometry. Apoptosis was detected by Hoechst 33258 and Annexin-V/propidium iodide staining. Mitochondrial membrane potential was determined by staining with a JC-1 probe, flow cytometry and fluorescence microscopy. Protein expression was detected by western blotting. The results revealed that β-ELE significantly inhibited the proliferation of various bladder cancer cell lines and induced cell cycle arrest at G0/G1-phase in T24 and 5637 cells. Compared with cisplatin alone, co-treatment with β-ELE increased cisplatin-mediated cytotoxicity against T24 cells, which resulted in the loss of mitochondrial membrane potential and release of cytochrome c into the cytoplasm. Co-treatment with β-ELE and cisplatin enhanced ROS accumulation and activation of 5′AMP-activated protein kinase (AMPK), which induced apoptosis. The results of the present study suggested that β-ELE inhibited the proliferation of bladder cancer cells in vitro and enhanced cisplatin-induced mitochondria-dependent apoptosis via the ROS-AMPK signaling pathway. Combination therapy with β-ELE requires further investigation as a potential treatment of bladder cancer.

Cell suspension culture of Rhizoma zedoariae in a two-stage perfusion bioreactor system for β-elemene production

We presented a two-stage combined bioreactor system consisting of a stir-tank and an airlift column, and challenged with Rhizoma zedoariae cell suspensions for β-elemene production. Two-stage culture was initiated when the cell concentration in both vessels was maintained at an appropriate density. The cells were proliferated in stirred-tank with the maximal growth rate of 0.17 d−1 to present enough cells for β-elemene synthesis. In the airlift column, continuous cell separation from culture medium was achieved by using a cell retention device based on centrifugal and gravity settling when the system was performed in perfusion mode. The results indicated that additives can efficiently promote the accumulation of β-elemene in R. zedoariae cells. In addition, the β-elemene content showed higher levels in cell lines of overexpressing 3-hydroxy-3-methylglutaryl coenzyme-A reductase, Farnesyldi phosphate synthase, and ST02C genes.

Liver-targeted delivery of liposome-encapsulated curcumol using galactosylated-stearate.

Liver-targeted drug delivery improves the efficacy of anti-liver cancer agents and reduces systemic toxicity by limiting the bioavailability of these drugs to within tumors. Liver targeting reagents with galactose residues, which selectively combine to asialoglyco protein receptors, have previously been used to improve liposome-encapsulated drug accumulation within liver cells. They lead to a reduction in liver cancer cell growth and have been used to cure certain hepatic diseases. In the present study, curcumol, which is the primary active component of Chinese traditional medicine Rhizoma zedoariae, was encapsulated in galactosylated-liposomes to enhance its anti-liver cancer efficacy. Galactosylated-liposomes and normal liposomes were labeled with propidium iodide. Galactosylated-liposomes with increasing concentrations of galactosylated-stearate (Gal-s) had a notably increased level of uptake in HepG2 cells (hepatoblastoma) compared with SGC-7901 (gastric cancer) and A549 (non-small cell lung cancer) cells. When the percentage of Gal-s reached 20%, liposome uptake plateaued. In the in vitro anti-liver cancer experiment, the anti-liver cancer efficacy of galactosylated-curcumol-liposomes increased significantly more compared with normal curcumol liposomes and free curcumol as indicated by cell survival rate and lactate dehydrogenase release rate. Collectively, these results demonstrate that galactosylated-liposomes are able to enhance the in vitro liver-targeting effect and anti-liver cancer efficacy of curcumol.

β-elemene attenuates macrophage activation and proinflammatory factor production via crosstalk with Wnt/β-catenin signaling pathway

β-elemene, extracted from Rhizoma zedoariae, has been widely used as a traditional medicine for its antitumor activity against a broad range of cancers. However, the effect of β-elemene in inflammation disorders has yet to be determined. The present study was designed to investigate the anti-inflammatory effects and potential molecular mechanisms of β-elemene in lipopolysaccharide (LPS)-induced murine macrophage cells RAW264.7. We found that the production of pro-inflammatory mediators, including interleukin-6(IL-6), tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), induced by LPS was significantly suppressed by β-elemene in a dose-dependent manner in RAW264.7 macrophage cell line. Also, β-elemene inhibited LPS-induced nitric oxide synthase (iNOS) and interleukin-10 (IL-10) expression by RAW264.7, which was related to the down-regulation of Wnt/β-catenin signaling pathway. Importantly, this study demonstrates that β-catenin was significantly inhibited by β-elemene, which appeared to be largely responsible for the down-regulation of Wnt/β-catenin signaling pathway. Accordingly, the deletion of β-catenin in primary macrophages reversed β-catenin-elicited inhibition of immune response. Furthermore, β-catenin expression and Wnt/β-catenin signaling pathway induced by LPS in RAW264.7 was also significantly inhibited by α-humulene, one isomeric sesquiterpene of β-elemene. α-humulene was also found to significantly inhibit LPS-induced production of proinflammatory cytokines. However, α-humulene showed more cytotoxic ability than β-elemene. Collectively, our data illustrated that β-elemene exerted a potent inhibitory effect on pro-inflammatory meditator and cytokines production via the inactivation of β-catenin, and also demonstrated the protective functions of β-elemene in endotoxin-induced inflammation. β-elemene may serve as potential nontoxic modulatory agents for the prevention and treatment of inflammatory diseases.

Molecular Mechanisms of Anti-cancer Activities of β-elemene: Targeting Hallmarks of Cancer.

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.

The reversal of antineoplastic drug resistance in cancer cells by β-elemene.

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.

β-elemene inhibited expression of DNA methyltransferase 1 through activation of ERK1/2 and AMPKα signalling pathways in human lung cancer cells: the role of Sp1.

β-elemene, a compound derived from Rhizoma zedoariae, is a promising new plant-derived drug with broad-spectrum anticancer activity. However, the underlying mechanism by which this agent inhibits human lung cancer cell growth has not been well elucidated. In this study, we showed that β-elemene inhibits human non-small cell lung carcinoma (NSCLC) cell growth, and increased phosphorylation of ERK1/2, Akt and AMPKα. Moreover, β-elemene inhibited expression of DNA methyltransferase 1 (DNMT1), which was not observed in the presence of the specific inhibitors of ERK (PD98059) or AMPK (compound C). Overexpression of DNMT1 reversed the effect of β-elemene on cell growth. Interestingly, metformin not only reversed the effect of β-elemene on phosphorylation of Akt but also strengthened the β-elemene-reduced DNMT1. In addition, β-elemene suppressed Sp1 protein expression, which was eliminated by either ERK1/2 or AMPK inhibitor. Conversely, overexpression of Sp1 antagonized the effect of β-elemene on DNMT1 protein expression and cell growth. Taken together, our results show that β-elemene inhibits NSCLC cell growth viaERK1/2- and AMPKα-mediated inhibition of transcription factor Sp1, followed by reduction in DNMT1 protein expression. Metformin augments the effect of β-elemene by blockade of Akt signalling and additively inhibition of DNMT1 protein expression. The reciprocal ERK1/2 and AMPKα signalling pathways contribute to the overall responses of β-elemene. This study reveals a potential novel mechanism by which β-elemene inhibits growth of NSCLC cells.

β-elemene, a compound derived from Rhizoma zedoariae, reverses multidrug resistance mediated by the ABCB1 transporter

In the present in vitro study, we examined the effect of the compound β-elemene on the response of KB-C2 cells overexpressing the ABCB1 transporter to specific antineoplastic compounds. The MTT assay was used to determine the effects of β-elemene in combination with other anticancer drugs on ABCB1-overexpressing cancer cell lines. Furthermore, we used [3H]-paclitaxel accumulation, efflux assay, immunofluorescence experiments, western blot assays and docking analysis to ascertain the mechanism of action of β-elemene. The incubation of KB-C2 cells overexpressing ABCB1 transporter with β-elemene (100 µM) significantly augmented the antineoplastic efficacy of colchicine, vinblastine and paclitaxel when compared to KB-C2 cells incubated with these drugs alone. In HEK293 cells overexpressing the ABCB1 transporter, β-elemene significantly increased the cytotoxicity of paclitaxel. In addition, 100 µM of β-elemene significantly increased the accumulation of [3H]-paclitaxel and this was due to a decrease in [3H]-paclitaxel efflux when compared to controls. The incubation of KB-C2 cells with β-elemene (100 µM) for 72 h did not significantly alter the expression of ABCB1 protein levels. Immunofluorescence experiments indicated that β-elemene did not significantly alter the subcellular localization of the ABCB1 transporter. Docking analysis indicated that β-elemene binds to the drug-binding site of ABCB1 transporter. Finally, β-elemene at 100 µM partially (~50%) increased the sensitivity of the BCRP-overexpressing cell line, NCI-H460/MX20, to mitoxantrone, but β-elemene did not significantly alter the resistance of MRP1-transfected HEK293/MRP1 cells to vincristine. Overall, our in vitro findings indicated that β-elemene potentiates the cytotoxic effects of various antineoplastic drugs in cell lines overexpressing the ABCB1 transporter and that this is due to the inhibition of the efflux component of the ABCB1 transporter.

Enhancement of cisplatin-induced apoptosis by β-elemene in resistant human ovarian cancer cells

β-Elemene is a new anticancer compound extracted from the Chinese medicinal herb Rhizoma zedoariae. We have shown previously that β-elemene increases cisplatin cytotoxicity and enhances cisplatin sensitivity via blocking cell cycle progression at G2/M phase in resistant ovarian tumor cells. In the current study, we asked whether β-elemene-augmented cisplatin activity in ovarian carcinoma cells is mediated through the induction of apoptosis. Here, we show that β-elemene triggered apoptotic cell death in chemoresistant human ovarian cancer A2780/CP and MCAS cells in a dose- and time-dependent fashion, as assessed by six different apoptosis assays. Intriguingly, β-elemene was a stronger inducer of apoptosis than cisplatin in this model system, and a synergistic effect on induction of cell death was observed when the tumor cells were treated with both agents. Furthermore, β-elemene plus cisplatin exposure significantly disrupted the mitochondrial transmembrane potential (ΔΨ (m)) and increased the release of cytochrome c from mitochondria into the cytoplasm. The combination treatment with both compounds also induced increases in caspase-3/8/9 activities and caspase-9 cleavage, enhanced protein expression of Bax and phosphorylation of Bcl-2 at Ser-70, and reduced the protein levels of Bcl-2 and Bcl-X(L) in the platinum-resistant ovarian cancer cells. Taken together, these data indicate that β-elemene sensitizes chemoresistant ovarian carcinoma cells to cisplatin-induced apoptosis and that the augmented effect of β-elemene on cisplatin cytotoxicity and sensitivity in resistant ovarian tumor cells is mediated through a mitochondria- and caspase-dependent cell death pathway.

Elemene for the treatment of lung cancer

Elemene, isolated from the Chinese medicinal herb Rhizoma Zedoariae and be used to treat patients with lung cancer in China. Until now, the effects have not been systematically reviewed. The purpose of this review was to determine the effectiveness and safety of elemene in the treatment of patients with lung cancer. We searched according to the strategy suggested by Lung Cancer group: the Cochrane Central Register of Controlled Trials (The Cochrane Library 2006, Issue 2); MEDLINE (1966 to June 2006); EMBASE (1974 to June 2006); OVID (1950 to June, 2006); CBMdisc on Chinese Biomedical Literature (Issue 1 2004 Chinese Language) and CNKI (Chinese Knowledge Internet 1994 to June 2006). Only randomised controlled trials (RCTs) that compared elemene with chemotherapy agents, radiotherapy, surgery, physical therapy or other effective Chinese herb therapy, either alone or in combination, had been sought in this review, regardless of language or publication status. Two authors telephoned the original trial authors of claimed randomised controlled trials and made a decision about trial inclusion and exclusion. We identified 20 trials which claimed to use random allocation. Sixteen study authors were contacted by telephone and we discovered that they misunderstood the randomisation procedure and the trials were identified as non-RCTs. We were unable to contact the authors of the remaining four studies and these have been allocated to the 'Studies awaiting assessment' section. There is no evidence from randomised controlled trials to confirm or refute the effectiveness of elemene as a treatment for lung cancer. Randomised clinical trials, on elemene for the treatment of lung cancer are needed in order to define the efficacy and acceptability of elemene for lung cancer.

Natural products of plant origin as anticancer agents.

Natural products have been used as effective remedies for the treatment of various ailments. Numerous plant products in the form of decoction, tincture, tablets and capsules have been clinically used for the treatment of different kinds of cancer. This review covers some of the important plants with clinically proven anticancer activity, including Catharanthus roseus, Podophyllum peltatum, Taxus brevifolia, Camptothecin acuminata, Cephalotaxus harringtonia, Viscum album, Onchrosia elliptica, Annona bullata, Asmina triloba and Rhizoma zedoariae. Synthetic analogues in some cases have also been prepared to improve the efficacy and decrease the side effects of parent compounds. The modes of action of clinically used drugs are also delineated.

The antitumor activity of elemene is associated with apoptosis

Elemene, isolated from the Chinese medicinal herb Rhizoma Zedoariae was shown to exhibit antitumor activityin vitro andin vivo to human and murine tumor cells. This novel antineoplastic agent has been demonstrated to have substantial clinical activity against various tumors. In this paper, the mechanisms of antitumor activity of elemene are reported. Thein vitro effect of elemene on the growth of leukemia cells was evaluated by MTT assay. The ICs, values of elemene for promyelocytic leukemia HL-60 cells and erythroleukemia K562 cells were found to be 27.5 µg/ml and 81 µg/ml, respectively, while IC50 for peripheral blood leukocytes (PBL) was 254 J µg/ml. The inhibitory effect of elemene on proliferation of HL-60 cells was associated with cell cycle arrest from S to G2M phase transition and with induction of apoptosis. The apoptosis of tumor cells was confirmed by DNA ladder formation on gel electrophoresis and characteristic ultrastructural alternations. These results indicate that induction of apoptosis contributes to the mechanisms of antitumor activity of elemene.

Initial study on naturally occurring products from traditional Chinese herbs and vegetables for chemoprevention

A number of naturally occurring products from vegetables and herbs exert chemopreventive properties against carcinogenesis. In this paper, two such compounds, isolated from garlic and from a traditional Chinese medicinal herb, are described for review. Elemene, isolated from the Chinese medicinal herb Rhizoma zedoariae, was shown to exhibit antitumor activity in human and murine tumor cells in vitro and in vivo. This novel antineoplastic agent has substantial clinical activity against various tumors. The in vitro effect of elemene on the growth of leukemia cells was evaluated by MTT assay. The IC50 values of elemene for promyelocytic leukemia HL-60 cells and erythroleukemia K562 cells were 27.5 micrograms/mL and 81 micrograms/mL, respectively, while IC50 for peripheral blood leukocytes (PBL) was 254.3 micrograms/mL. The inhibitory effect of elemene on proliferation of HL-60 cells was associated with cell cycle arrest from S to G2M phase transition and with induction of apoptosis. The apoptosis of tumor cells was confirmed by DNA ladder formation on gel electrophoresis and characteristic ultrastructural alterations. The results also demonstrated that inhibitory effects of allicin, a natural organosulfide from garlic, on proliferation of tumor cells were associated with the cell cycle blockage of S/G2M boundary phase and induction of apoptosis. These findings suggest that induction of apoptosis may contribute to the mechanisms of antitumor activity of elemene and allicin, which merit investigation as potential chemoprevention agents in humans.