Synergistic property of cordycepin in cultivated Cordyceps militaris-mediated apoptosis in human leukemia cells.
Cordyceps militaris is a well-known Chinese traditional medicinal mushroom frequently used for tonics and recently of a potential interest for cancer intervention. Here, we explored the cancer cell killing activity of the hot water extracts of C. militaris cultured mycelia ([CM.sub.MY]) and cultivated fruiting bodies ([CM.sub.FB]). We found that [CM.sub.FB] exhibited a greater cytotoxic effect against various cancer cells over [CM.sub.MY]. Apoptotic phenotypes including apoptotic body formation, DNA laddering, caspase 3 activation and cleavage of PARP proteins were induced by [CM.sub.FB] treatment but only slightly induced by same concentration of [CM.sub.MY] treatment in human HL-60 leukemia cells. Cordycepin in [CM.sub.FB] (10.47 mg/g) is significantly higher (~15.2 times) than that of [CM.sub.MY] (0.69 mg/g). Using isobolographic analysis, the synergy of cytotoxicity was observed across different combined concentrations of [CM.sub.MY] and cordycepin. By complementing cordycepin into [CM.sub.MY] to the level comparable with CMFB, we observed that [CM.sub.MY] (500 [micro]g/ml) with cordycepin (4.8 [micro]g/ml) induced apoptosis to a level similar to that induced by [CM.sub.FB] (500 [micro]g/ml). Together, our results suggest that cordycepin possesses a synergistic cytotoxic effect with Cordyceps militaris-mediated apoptosis in human leukemia cells and therefore explaining a better anti-proliferating activity of [CM.sub.FB] over [CM.sub.MY]
Aloe-emodin novel anticancer Herbal Drug Khemkaran Ahirwar1 * Sanmati K. Jain1
Abstract The electrochemical behaviour of the anticancer herbal drug emodin hydroxyanthraquinone present in Aloe vera leaves has a specific in vitro and in vivo antineuroectodermal tumor activity. The compound does not inhibit the proliferation of normal fibroblasts n or that of hemopoietic progenitor cells. The cytotoxicity mechanism consists of the induction of apoptosis, whereas the selectivity against neuroectodermal tumor cells is founded on a specific energy-dependent pathway of drug incorporation. Natural compounds that have traditionally been used to treat a variety of diseases for hundreds of years (1, 2, 3) . We assayed only those natural compounds that have already been proven to be nontoxic, and we evaluated their efficacy against highly malignant tumors that are not normally included in the classical screening assays.
Conclusion: Aloe-Emodin was able to inhibit cell growth in several tumor cells, including human lung carcinoma, 10 hepatoma, 11 and leukemia cell lines. 13 aloe-emodin shows a high specificity for neuroectodermal tumor cells. 14 one of the important approaches for cancer chemotherapy is to regulate cell-cycle progression. G1/S cell-cycle arrest was found in human hepatoma, 12 glioma, 16 breast, 10 lung, 11 and colon 15 carcinoma cells upon treatment of rhubarb anthraquinones (emodin, 9 aloe-emodin, 13 and rhein 16 The herbal medicines have great importance in the treatment of many diseases. Since herbal medicines are mainly used by Chinese, but now gaining acceptance all over the world and mostly in India. Herbal plants and their derivatives are widely used in the treatment of cancer. The treatment of cancer must include the benefits of botanical medicines. There are many classes of plant-derived cytotoxic natural products and the structural modification studies for further improvement and development of drug. New anticancer drugs derived from research on plant antitumor agents will be continuously discovered. The activities of flavonoids and the synergistic action shown by them with other drugs make them ideal in alternative cancer therapies. The chemopreventive effects that most flavonoids exert are likely to be the sum of their effect on several distinct mechanisms working inside the cell. The flavonoids have been focused for the research since 1930’s but many of them have been used in traditional medicines for thousands of years in eastern countries. Anthraquinones are an important group of bioactive components found in many species of medicinal herbs such as rhubarb, senna, aloe and purslane. Induction of apoptosis is commonly reported among emodin and aloe-emodin, which involve disruption of mitochondria membrane potential, cytochrome c release, and activation of caspase 3. Emodin and aloe-emodin were also able to induce cell-cycle arrest, involving an increase in p53 expression level and accompanied by upregulation of p21. This suggests that emodin could be a promising candidature for the research and development of new anti-tumor drugs.
Tumor Therapy with Amanita phalloides (Death Cap): Stabilization of B-Cell Chronic Lymphatic LeukemiaIsolde Riede, PhD
Alternative Practitioner, Independent Cancer Research, Ueberlingen, Germany.
Abstract . Molecular events that cause tumor formation upregulate a number of HOX genes, called switch genes, coding for RNA polymerase II transcription factors. Thus, in tumor cells, RNA polymerase II is more active than in other somatic cells. Amanita phalloides contains amanitin, inhibiting RNA polymerase II. Partial inhibition with amanitin influences tumor cell—but not normal cell—activity.
Objectives To widen the treatment spectrum, homeopathic dilutions of Amanita phalloides, containing amanitin, were given to a patient with leukemia. Monitoring the leukemic cell count, different doses of amanitin were given.
Results The former duplication time of leukemic cells was 21 months. Within a period of 21 months, the cell count is stabilized to around 105/μL. No leukemia-associated symptoms, liver damage, or continuous erythrocyte deprivation occur.
Conclusions This new principle of tumor therapy shows high potential to provide a gentle medical treatment.
Source : J Altern Complement Med. 2010 October; 16(10): 1129–1132 Link to Full Article . Apoptosis induced by the Tibetan herbal remedy PADMA 28 in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2 Marcel Jenny1, Wolfgang Schwaiger1, David Bernhard2, Oliver A Wrulich1, Daria Cosaceanu3, Dietmar Fuchs4, Florian Ueberall1
1 Division of Medical Biochemistry, Biocenter, Innsbruck Medical School, Fritz Pregl-str. 3, 6020, Innsbruck, Austria 2 Division of Experimental Pathophysiology and Immunology, Biocenter, Innsbruck Medical School, Fritz Pregl-str.3, 6020, Innsbruck, Austria 3 Department of Oncology-Pathology, Karolinska Institute, Cancer Centrum R 8:00, 17176, Stockholm, Sweden 4 Division of Biological Chemistry, Biocenter, Innsbruck Medical School, Fritz Pregl-Str. 3, 6020, Innsbruck, Austria
.PADMA28 It is a mixture of a variety of different herbs (403 mg of active ingredients): Aegle marmelos (Bengal Quince) fruit (20 mg); Pimenta dioica (Allspice) fruit (25 mg); Aquilegia vulgaris (Columbine) aerial part (15 mg); Calendula officinalis (Marigold) flower (5 mg); Elettaria cardamomum (Cardamom) fruit (30 mg); Syzygium aromaticum (Clove) flower bud (12 mg); Saussurea lappa (Saussuria) root (40 mg); Hedychium spicatum (Hedychium) rhizome (10 mg); Lactuca sativa (Lettuce) leaf (6 mg); Cetraria islandica (Iceland moss) thallus (40 mg); Glycyrrhiza glabra (Licorice) root (15 mg); Azadirachta indica (Margosa) fruit (35 mg); Terminalia chebula (Myrobalan) fruit (30 mg); Plantago lanceolata (Ribwort) aerial part (15 mg); Polygonum aviculare (Knot-grass) aerial part (15 mg); Potentilla aurea (Golden Cinquefoil) aerial part (15 mg); Pterocarpus santalinus (Red Sandalwood) wood (30 mg); Sida cordifolia (Heart-leaved Sida) aerial part (10 mg); Valeriana officinalis (Valerian) root (10 mg); and Aconitum napellus (Monkshood) tuber (1 mg). Also present are 2 non-herbal components: Dextrocamphora (natural camphor) (4 mg) and Calcii sulphas pulv .(Gipsum; 20 mg).
The Tibetan herbal remedy PADMA 28 revealed promising results to support treatment of atherosclerosis, Charot syndrome (intermittent claudication), chronic active hepatitis and infection of the respiratory tract. The remedy was confirmed to be closely linked with anti- and pro-oxidative properties in vitro . In this study, apoptogenic and survival effects of PADMA 28 were investigated in the T cell-derived lymphocytic leukaemia cell line CEM-C7H2. PADMA 28 led to a concentration-dependent inhibition of cell proliferation accompanied by the accumulation of CEM-C7H2 cells in subG1 phase, fragmentation of poly (ADP-ribose) polymerase (PARP) and nuclear body formation. Treatment with PADMA 28 rescued to some extent cells over-expressing Bcl-2 from apoptosis. This finding suggests that the mechanism of action of PADMA 28 may be via interference with Bcl-2 triggered survival pathways.
Here we show that PADMA 28 added to T cell-derived lymphatic leukaemia cells in culture has a pronounced concentration- and time-dependent anti-proliferative effect. The inhibition of cell proliferation is accompanied by nuclear body formation a morphological signs of apoptosis. Furthermore hallmarks of apoptosis, such as the accumulation of cells in subG1 phase, and fragmentation of poly (ADP-ribose) polymerase (PARP) could be detected.
A growing body of evidence demonstrates that cell survival and cell death are largely determined by the function of Bcl-2 family members. Here we show that induction of apoptosis by PADMA 28 can be effectively counteracted by overexpression of the pro-survival protein Bcl-2. Based on our data we suggest that PADMA 28 may act in a pro-apoptotic fashion by interfering with Bcl-2 signalling.......
Induction of apoptosis by shikonin through a ROS/JNK-mediated process in Bcr/Abl-positive chronic myelogenous leukemia (CML) cells Xin Mao1,*, Chun Rong Yu1,*, Wen Hua Li1 and Wen Xin Li1
1State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China
Abstract This study examined the signaling events induced by shikonin that lead to the induction of apoptosis in Bcr/Abl-positive chronic myelogenous leukemia (CML) cells (e.g., K562, LAMA84). Treatment of K562 cells with shikonin (e.g., 0.5 μM) resulted in profound induction of apoptosis accompanied by rapid generation of reactive oxygen species (ROS), striking activation of c-Jun-N-terminal kinase (JNK) and p38, marked release of the mitochondrial proteins cytochrome c and Smac/DIABLO, activation of caspase-9 and -3, and cleavage of PARP. Scavenging of ROS completely blocked all of the above-mentioned events (i.e., JNK and p38 phosphorylation, cytochrome c and Smac/DIABLO release, caspase and PARP cleavage, as well as the induction of apoptosis) following shikonin treatment. Inhibition of JNK and knock-down of JNK1 significantly attenuated cytochrome c release, caspase cleavage and apoptosis, but did not affect shikonin-mediated ROS production. Additionally, inhibition of caspase activation completely blocked shikonin-induced apoptosis, but did not appreciably modify shikonin-mediated cytochrome c release or ROS generation. Altogether, these findings demonstrate that shikonin-induced oxidative injury operates at a proximal point in apoptotic signaling cascades, and subsequently activates the stress-related JNK pathway, triggers mitochondrial dysfunction, cytochrome c release, and caspase activation, and leads to apoptosis. Our data also suggest that shikonin may be a promising agent for the treatment of CML, as a generator of ROS.
.Shikonin (C16H16O5) is a natural naphthoquinone derivative compound that is present in the root tissues of the traditional Chinese medical herb Lithospermum erythrorhizon. This herb is found throughout China, including in Southern Yun Nan, Northern Dong Bei, Western Xin Jiang and Tibet. Lithospermum erythrorhizon was first recorded in a 2000-year-old Chinese medical material dictionary “Materia Medica of Deity of Agriculture”, also called “Shen Nong Ben Cao Jing” 1. This dictionary was compiled around the time of the Qin (225 BC–206 BC) and Han (206 BC–220 AD) dynasties.
Thymoquinone rich fraction from Nigella sativa and thymoquinone are cytotoxic towards colon and leukemic carcinoma cell lines Ismail Norsharina1,2, Ismail Maznah1,2*, Al-Absi Aied1 and Al-Naqeeb Ghanya1,2
1Nutrigenomics and Nutricosmeceuticals Programme, Laboratory of Molecular Biomedicine, Institute of Bioscience, Universiti Putra Malaysia, UPM 43400 Serdang, Selangor Darul Ehsan, Malaysia. 2Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, UPM 43400 Serdang, Selangor Darul Ehsan, Malaysia.
Nigella sativa has been used for centuries in Asia, Middle East and Africa to promote health and fight diseases. In this study, the anti-cancer effects of thymoquinone rich fraction (TQRF) extracted from N.sativa seeds using supercritical fluid extraction (SFE) system and commercially available thymoquinone (TQ) on colon cancer (HT29), lymphoblastic leukemia (CEMSS) and promyelocytic leukemia (HL60) cells lines were investigated. The concentration that gave 50% inhibition of cell viability (IC50) of HT29, CEMSS and HL60 cells treated with TQRF were 400, 350 and 250 μg/ml, respectively. Meanwhile, the IC50 of TQ was 8, 5 and 3 μg/ml, respectively. Cell cycle analysis shows the increment of apoptosis in a time-dependent manner. However, both TQRF and TQ were not able to arrest the cell cycle phases of the cells. Apoptosis was the main mode of HT29, CEMSS and HL60 cells death induced by both TQRF and TQ. Our findings support the potential use of TQRF and TQ for the treatment of colon cancer and leukemia.
....In conclusion, this study indicates that TQRF and TQ possess cytotoxic properties against colorectal cancer and showed more prominent cytotoxic effects on leukemic cell lines. In spite of TQ, TQRF was also has potential to be used as anti-cancer treatment. Therefore, TQRF from N. sativa does have the potential to be developed as a nutraceuticals for preventing the progression of cancer.
Source : Journal of Medicinal Plants Research Vol. 5(15), pp. 3359-3366, 4 August, 2011 Link to Full Article
Triptolide Inhibits Bcr-Abl Transcription and Induces Apoptosis in STI571-resistant Chronic Myelogenous Leukemia Cells Harboring T315I Mutation Xianping Shi1,Yanli Jin1,Chao Cheng2,Hui Zhang5,Waiyi Zou3,Qin Zheng1,Zhongzheng Lu1,Qi Chen1,Yingrong Lai4 and Jingxuan Pan1
Purpose: Resistance to STI571 is an emerging problem for patients with chronic myelogenous leukemia (CML). Mutation in the kinase domain of Bcr-Abl is the predominant mechanism of the acquired resistance to STI571. In the present study, we investigated the effect of triptolide on cell survival or apoptosis in CML cells bearing Bcr-Abl-T315I or wild-type Bcr-Abl.
Experimental Design: CML cell lines (KBM5 versus KBM5-T315I, BaF3-Bcr-Abl versus BaF3-Bcr-Abl-T315I) and primary cells from CML patients with clinical resistance to STI571 were treated with triptolide, and analyzed in terms of growth, apoptosis, and signal transduction. Nude mouse xenograft model was also used to evaluate the antitumor activity.
Results: Triptolide potently down-regulated the mRNA and protein levels of Bcr-Abl independently of the caspase or proteosome activation in CML cells. It induced mitochondrial-dependent apoptosis in Bcr-Abl-T315I CML cells and primary cells from CML patients with clinical resistance to STI571. Additionally, triptolide inhibited the growth of STI571-sensitive KBM5 and STI571-resistant KBM5-T315I CML cells in nude mouse xenografts. Triptolide also down-regulated the expression of survivin, Mcl-1, and Akt in CML cells, which suggests that it may have multiple targets.
Conclusions:These findings suggest that triptolide is a promising agent to overcome STI571-resistant CML cells, and warrant a clinical trial of triptolide derivatives for CML with Bcr-Abl-T315I mutation.
NOTE Traditional Chinese medicine has used Tripterygium wilfordii Hook. f. for centuries to treat inflammation and autoimmune diseases (18–21). Among the many small molecules extracted and purified from this shrub-like vine, triptolide is the key biologically active component that mediates immunosuppression and anti-inflammation (20, 22). Of note, PG490-88, a water-soluble derivative of triptolide, has been under investigation as an immunosuppressant in a clinical trial of organ transplantation (23). Triptolide is a potent inhibitor of nuclear factor-κB– and NF-AT–mediated transcription (24). In addition, it has antitumor activities against a broad range of human cancer cells (25–28). For instance, it decreases XIAP and Mcl-1 levels and triggers apoptosis in acute myeloid leukemia cells (26). It also sensitizes tumor cells to apoptosis stimuli such as Apo2/TRAIL, tumor necrosis factor α, and various chemotherapeutic agents (29–32). Interestingly, it also down-regulates Bcr-Abl expression in K562 cells via an unknown mechanism (33).
We hypothesized that triptolide has antineoplastic activity against CML cells including STI571-resistant cells by down-regulating Bcr-Abl and, so, evaluated its translational efficacy against CML cells with wild-type or T315I-mutant Bcr-Abl. Here, we report the antineoplastic effect of triptolide against CML cell lines (including STI571-resistant lines) and primary cells from CML patients in cell culture and in mouse xenograft models. Triptolide may be a promising agent to overcome STI571- resistance caused by the Bcr-Abl-T315I mutation.
Induction of Apoptosis in Human Leukemia Cells by Grape Seed Extract Occurs via Activation of c-Jun NH2-Terminal Kinase
Zhuo Zhang2 and
Abstract Purpose: To characterize the functional role of c-Jun NH2-terminal kinase (JNK) and other apoptotic pathways in grape seed extract (GSE)-induced apoptosis in human leukemia cells by using pharmacologic and genetic approaches.
Experimental Design: Jurkat cells were treated with various concentrations of GSE for 12 and 24 h or with 50 μg/mL GSE for various time intervals, after which apoptosis, caspase activation, and cell signaling pathways were evaluated. Parallel studies were done in U937 and HL-60 human leukemia cells.
Results: Exposure of Jurkat cells to GSE resulted in dose- and time-dependent increase in apoptosis and caspase activation, events associated with the pronounced increase in Cip1/p21 protein level. Furthermore, treatment of Jurkat cells with GSE resulted in marked increase in levels of phospho-JNK. Conversely, interruption of the JNK pathway by pharmacologic inhibitor (e.g., SP600125) or genetic (e.g., small interfering RNA) approaches displayed significant protection against GSE-mediated lethality in Jurkat cells.
Conclusions:The result of the present study showed that GSE induces apoptosis in Jurkat cells through a process that involves sustained JNK activation and Cip1/p21 up-regulation, culminating in caspase activation.
A randomized, controlled, double-blind, pilot study of milk thistle for the treatment of hepatotoxicity in childhood acute lymphoblastic leukemia (ALL)
Elena J. Ladas MS, RD1,
David J. Kroll PhD2,
Nicholas H. Oberlies PhD3,
Bin Cheng PhD4,
Deborah H. Ndao MPH1,
Susan R. Rheingold MD5,
Kara M. Kelly MD1,*,
Abstract BACKGROUND:Despite limited preclinical and clinical investigations, milk thistle (MT) is often used for the treatment of chemotherapy-associated hepatotoxicity. Limited treatment options exist for chemotherapy-related hepatoxicity. Given the wide use of MT, the authors investigated MT in both the laboratory and a clinical setting.
METHODS:In a double-blind study, children with acute lymphoblastic leukemia (ALL) and hepatic toxicity were randomized to MT or placebo orally for 28 days. Liver function tests were evaluated during the study period. To assess MT in vitro, the authors evaluated supratherapeutic concentrations in an ALL cell line.
RESULTS:Fifty children were enrolled. No significant differences in frequency of side effects, incidence and severity of toxicities, or infections were observed between groups. There were no significant changes in mean amino alanine transferase (ALT), aspartate amino transferase (AST), or total bilirubin (TB) at Day 28. At Day 56, the MT group had a significantly lower AST (P = .05) and a trend toward a significantly lower ALT (P = .07). Although not significantly different, chemotherapy doses were reduced in 61% of the MT group compared with 72% of the placebo group. In vitro experiments revealed no antagonistic interactions between MT and vincristine or L-asparaginase in CCRF-CEM cells. A modest synergistic effect with vincristine was observed.
CONCLUSIONS:In children with ALL and liver toxicity, MT was associated with a trend toward significant reductions in liver toxicity. MT did not antagonize the effects of chemotherapy agents used for the treatment of ALL. Future study is needed to determine the most effective dose and duration of MT and its effect on hepatotoxicity and leukemia-free survival.
Anti-cancer Effects of Protein Extracts from Calvatia lilacina, Pleurotus ostreatus and Volvariella volvacea Jin-Yi Wu1, Chi-Hung Chen2, Wen-Huei Chang3, King-Thom Chung4, Yi-Wen Liu1, Fung-Jou Lu5 and Ching-Hsein Chen1,* 1Graduate Institute of Biomedical and
Biopharmaceutical Sciences, College of Life Sciences, 2Graduate Institute of Food Science and Biopharmaceutics, National Chiayi University, Chiayi, 3Department of Chemical Biology, National Pingtung University of Education, Pingtung, Taiwan, 4Department of Biology, The University of Memphis, Memphis, TN, USA and 5Department of Applied Chemistry, Chung Shan Medical University, Taichung, Taiwan
Calvatia lilacina (CL), Pleurotus ostreatus (PO) and Volvariella volvacea (VV) are widely distributed worldwide and commonly eaten as mushrooms. In this study, cell viabilities were evaluated for a human colorectal adenocarcinoma cell line (SW480 cells)and a human monocytic leukemia cell line (THP-1 cells). Apoptotic mechanisms induced by the protein extracts of PO and VV were evaluated for SW480 cells. The viabilities of THP-1 and SW480cells decreased in a concentration-dependent manner after 24h of treatment with the protein extracts of CL, PO or VV. Apoptosis analysis revealed that the percentage of SW480 cells in theSubG1 phase (a marker of apoptosis) was increased upon PO andVV protein-extract treatments, indicating that oligonucleosomal DNA fragmentation existed concomitantly with cellular death.The PO and VV protein extracts induced reactive oxygen species(ROS) production, glutathione (GSH) depletion and mitochondrial transmembrane potential (m) loss in SW480 cells. Pretreatment with N-acetylcysteine, GSH or cyclosporine A partially prevented the apoptosis induced by PO protein extracts, but not that induced by VV extracts, in SW480 cells. The protein extracts of CL,PO and VV exhibited therapeutic efficacy against human colorectal adenocarcinoma cells and human monocytic leukemia cells. The PO protein extracts induced apoptosis in SW480 cells partially through ROS production, GSH depletion and mitochondrial dysfunction.Therefore, the protein extracts of these mushrooms could be considered an important source of new anti-cancer drugs.
Source: eCAM Advance Access published online on May 18, 2010 eCAM, doi:10.1093/ecam/neq05 LINK TO FULL ARTICLE
Cytotoxic and antibacterial activities of endophytic fungi isolated from plants at the National Park, Pahang, Malaysia Nurul AMN Hazalin,1 Kalavathy Ramasamy,1 Siong Meng Lim,1 Ibtisam Abdul Wahab,2 Anthony LJ Cole,3 and Abu Bakar Abdul Majeed4
1Collaborative Drug Discovery Research (CDDR) Group, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor Darul Ehsan, Malaysia 2Institute for the Study of Natural Remedies (iKUS), Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor Darul Ehsan, Malaysia 3School of Biological Sciences, University of Canterbury, Private Bag 4800, Christchurch, New Zealand 4Brain Research Laboratory, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), 40450 Shah Alam, Selangor Darul Ehsan, Malaysia
Abstract Background Endophytes, microorganisms which reside in plant tissues, have potential in producing novel metabolites for exploitation in medicine. Cytotoxic and antibacterial activities of a total of 300 endophytic fungi were investigated.
Methods Endophytic fungi were isolated from various parts of 43 plants from the National Park Pahang, Malaysia. Extracts from solid state culture were tested for cytotoxicity against a number of cancer cell lines using the MTT assay. Antibacterial activity was determined using the disc diffusion method
Results A total of 300 endophytes were isolated from various parts of plants from the National Park, Pahang. 3.3% of extracts showed potent (IC50 < 0.01 μg/ml) cytotoxic activity against the murine leukemic P388 cell line and 1.7% against a human chronic myeloid leukemic cell line K562. Sporothrix sp. (KK29FL1) isolated from Costus speciosus showed strong cytotoxicity against colorectal carcinoma (HCT116) and human breast adenocarcinoma (MCF7) cell lines with IC50 values of 0.05 μg/ml and 0.02 μg/ml, respectively. Antibacterial activity was demonstrated for 8% of the extracts.
Conclusion Results indicate the potential for production of bioactive agents from endophytes of the tropical rainforest flora.
Source: BMC Complement Altern Med. 2009; 9: 46. LINK TO SOURCE Polysaccharopeptides derived from Coriolus versicolor potentiate the S-phase specific cytotoxicity of Camptothecin (CPT) on human leukemia HL-60 cells
Background Polysaccharopeptide (PSP) from Coriolus versicolor (Yunzhi) is used as a supplementary cancer treatment in Asia. The present study aims to investigate whether PSP pre-treatment can increase the response of the human leukemia HL-60 cells to apoptosis induction by Camptothecin (CPT).
Methods We used bivariate bromodeoxyuridine/ propidium iodide (BrdUrd/PI) flow cytometry analysis to measure the relative movement (RM) of the BrdUrd positively labeled cells and DNA synthesis time (Ts) on the HL-60 cell line. We used annexin V/PI flow cytometry analysis to quantify the viable, necrotic and apoptotic cells. The expression of cyclin E and cyclin B1 was determined with annexin V/PI flow cytometry and western blotting. Human peripheral blood mononuclear cells were used to test the cytotoxicity of PSP and CPT.
Results PSP reduced cellular proliferation; inhibited cells progression through both S and G2 phase, reduced 3H-thymidine uptake and prolonged DNA synthesis time (Ts) in HL-60 cells. PSP-pretreated cells enhanced the cytotoxicity of CPT. The sensitivity of cells to the cytotoxic effects of CPT was seen to be the highest in the S-phase and to a small extent of the G2 phase of the cell cycle. On the other hand, no cell death (measured by annexin V/PI) was evident with the normal human peripheral blood mononuclear cells with treatment of either PSP or CPT.
Conclusion The present study shows that PSP increases the sensitization of the HL-60 cells to undergo effective apoptotic cell death induced by CPT. The pattern of sensitivity of cancer cells is similar to that of HL-60 cells. PSP rapidly arrests and/or kills cells in S-phase and did not interfere with the anticancer action of CPT. PSP is a potential adjuvant to treat human leukemia as rapidly proliferating tumors is characterized by a high proportion of S-phase cells.
Conclusion: Study results show that root extracts of Rubia Cordifolia is promisingly cytotoxic and they might have antitumor activity against myeloid leukemia and Histolytic lymphoma. None of the fraction of the extract was found to be cytotoxic against the normal cell line (HEK293) in the given range of concentration. So, this plant extracts may have clinical and therapeutic proposition in the most life threaten disease like cancer and further studies are required to investigate this plant as source of antineoplastic agents LINK TO SOURCE
Inhibitory Effect of Propolis on the Growth of Human Leukemia U937
a Department of Pharmacology and Toxicology, Cancer Research Institute, Tohoku Pharmaceutical University; b Department of Pharmacology, Tohoku Pharmaceutical University; and c Department of Educational Center, Tohoku Pharmaceutical University; Sendai 981–8558, Japan. Received November 6, 2003; accepted January 30, 2004
We have investigated the effect of propolis (CB Propolis) on the growth of human histiolytic lymphoma U937cells. We found that propolis strongly inhibited the growth of the cells and macromolecular synthesis in a dose and time-dependent manner by apoptosis. Propolis at 0.015—0.5m l/ml showed antitumor activity with an IC50 of 0.18m l/ml for 3 d. It also inhibits DNA, RNA and protein synthesis with an IC50 of 0.08, 0.17 and 4.3m l/ml, respectively. The inhibitory effect on DNA synthesis was partially irreversible. Moreover, an apoptotic DNA ladder and chromatin condensation were observed in the same concentration range in which cell growth was inhibited. The caspase inhibitor, Z-Asp-CH2-DCB, prevented DNA fragmentation. These results suggest that the antitumor activity of propolis occurs through the induction of apoptosis. Propolis may be useful as a cancer chemopreventive and chemotherapeutic agent.