Induction of Apoptosis and Phase-Cell Cycle Inhibition of G0-G1, S, G2-M of T47D Breast Cancer Cells on Treatment with Ethyl Acetate Fraction of Jackfruit Parasite Leaves (Macrosolen cochinensis) (original) (raw)
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Journal of Applied Pharmaceutical Science, 2018
The combination of Eleutherine palmifolia (L.) Merr (EP) and Macrosolen cochinchinensis (Lour.) Tiegh (MC) extracts has been proven an empirically potential cure for cancer. The aims of this research were to prove scientifically the anticancer potential of the combination of EP and MC as well as its effects on the cell cycle and the apoptosis of HeLa cancer cell. The MTT method was used to measure cytotoxic effects. The effect of inhibition of cell cycle and induction of cell apoptosis was measured by the flow cytometry method. The results showed that the combination of EP and MC gives an induction of apoptosis effect of HeLa cancer cell through inhibition of cell cycle in the G0-G1, S, and G2/M phases synergistically until it is synergist strong. Therefore, the combination of EP and MC can be recommended as a candidate drug for cancer therapy.
Cancer Letters, 1996
Viscum album L. (VAL) is a phytopreparation used in adjuvant cancer therapy with both immunostimulatory and DNA stabilizing properties at low drug concentrations and cytostatic/cytotoxic properties at higher concentrations. The present work examines the cytotoxic effects of VAL extracts produced from mistletoes grown on different host trees and of purified toxic proteins from VAL, such as the D-galactose-specific lectin I (ML I), the iV-acetyl-D-galactosamine-specific ML II and ML III, and crude viscotoxins towards cultured human lymphocytes. The decrease in the number of cultured lymphocytes and blast cells treated with whole plant extracts from VAL was host tree-specific. Nevertheless, there was no close correlation to the content of MLs or viscotoxins. Using the purified proteins, it became obvious that the cell killing was mediated by the induction of apoptosis, as measured by the appearance of a hypodiploid DNA peak using flow cytometry. ML III was the most effective to induce apoptosis, followed by ML II and ML I, while the viscotoxins and oligosaccharides from VAL did not. By measuring the surface expression of IL-2Ra chains, transferrin receptors and APO-Was molecules on non-apoptotic T cells, no significant changes were observed at low ML concentrations (1 q/ml), but their decrease at higher ones. Our findings suggest that there might be at least two different ways of cell killing operative in VAL-mediated cytotoxicity: (a) the typical apoptotic cell death with the appearance of hypo-diploid nuclei, and (b) a direct or indirect killing by damaging the cell membrane with subsequent influx of Ca*+ and of the DNA intercalating dye propidium iodide and cell shrinkage. These effects might not be exclusive, as they probably occur simultaneously.
Phytotherapy Research, 2010
Mistletoe preparations are frequently used by cancer patients because of their ability to stimulate the immunity and to improve the quality of life. Moreover mistletoe and its active substances (especially lectins) possess cytotoxic effect on various cancer cell lines. However, only little is known about its interaction with anticancer drugs. Therefore the cytotoxic and apoptosis-inducing effects of aqueous mistletoe extract (VA) and its interaction with doxorubicin (DOXO) were investigated in Jurkat cells. The results show that VA extract as well as DOXO exert cytotoxic effects on Jurkat cells in a dose-dependent manner. Cytotoxicity of DOXO was much stronger (LC 50 = 11.68 ng/mL) than that of VA extract (LC 50 = 35.67 mg/mL). Their combination led to synergism only at those concentrations that were highly cytotoxic alone. Both substances (alone and in combination) induced DNA fragmentation in Jurkat cells. In conclusion, an aqueous extract prepared from mistletoe tops exerted cytotoxic and apoptosis-inducing effects on Jurkat cells alone as well as in combination with DOXO.
Cancer Letters, 2008
Viscum album (Mistletoe) is one of the most widely used alternative cancer therapies. Aqueous mistletoe extracts (MT) contain the three mistletoe lectins I, II and III as one predominant group of biologically active agents. Although MT is widely used, there is a lack of scientifically sound preclinical and clinical data. In this paper, we describe for the first time the in vivo efficacy and mechanism of action of MT in lymphoblastic leukemia. For this purpose, we first investigated both the cytotoxic effect and the mechanism of action of two standardized aqueous MTs (MT obtained from fir trees (MT-A); MT obtained from pine trees (MT-P)) in a human acute lymphoblastic leukemia (ALL) cell line (NALM-6). MT-A, MT-P and ML-I inhibited cell proliferation as determined by Casy Ò Count analysis at very low concentrations with MT-P being the most cytotoxic extract. DNA-fragmentation assays indicated that dose-dependent induction of apoptosis was the main mechanism of cell death. Finally, we evaluated the efficacy of MT-A and MT-P in an in vivo SCID-model of pre-B ALL (NALM-6). Both MTs significantly improved survival (up to 55.4 days) at all tested concentrations in contrast to controls (34.6 days) without side effects.
MEDICINA- …, 2007
The molecular and cellular mechanisms by which mistletoe extracts exert their cytotoxic and immunomodulatory anti-tumoral effects are largely unknown. Active components in these preparations include lectins and viscotoxins. In this study we tested the hypothesis that Iscador preparations induce tumor regression by cell cycle inhibition and/or interference with apoptotic signaling pathways in tumor cells. Also a possible effect on angiogenesis, which is a prerequisite for tumor growth in vivo, is studied in endothelial cell cultures. Furthermore, we examined which apoptotic signaling route(s) is (are) activated by Iscador by studying specific pro-apoptotic proteins in cultured cells. To characterize these properties, human carcinoma cell lines of different origin, two lymphoma cell lines, one epidermis derived cell line, and two endothelial cell cultures were incubated with different concentrations of either Iscador ® Quercus Spezial, Iscador ® Malus Spezial, both containing defined concentrations of lectins, or Iscador ® Pinus containing low amounts of lectin, but a relatively high concentration of viscotoxins. Cell cycle kinetic parameters were measured by bromodeoxyuridine (BrdU) pulse labeling and spindle microtubule staining. Apoptotic responses were detected by M30 CytoDeath or Annexin V/ propidium iodide assays. Characterization of the apoptotic pathway(s) was performed by staining cells for amongst others active caspase 3 and cytochrome C (mitochondrial pathway), as well as active caspase 8 (death receptor pathway). The sensitivity to Iscador treatment varies strongly between different cell lines and also amongst the different Iscador ® preparations. In sensitive cell lines, including those derived from small cell lung cancer, adenocarcinoma of the lung and breast, B-cell lymphoma, as well as endothelial cell cultures, Iscador caused early cell cycle inhibition followed by apoptosis in a dose dependent manner. Amongst the low responders are cell lines derived from colorectal carcinoma. In general Iscador ® Malus exerted a stronger response than Iscador ® Quercus. Apoptosis was induced by activating the mitochondrial, but not the death receptor dependent pathway, at least in case of Iscador ® Quercus. Iscador ® Malus also seemed to induce apoptosis via the death receptor route, which may explain the higher sensitivity of cancer and endothelial cells to this preparation. Iscador ® Pinus, tested in the lymphoma cell lines, was found to induce mainly necrosis, most probably due to the viscotoxins present in these preparations.
Comparative study concerning mistletoe viscotoxins antitumor activity
Acta Biologica Hungarica, 2013
Viscum album l. (Santalaceae), VA, -a parasitic plant that grows on various trees -, has proved a significant anticancer effect in both experimental studies and clinical trials. The present study assesses the influence of oxidative stress in mistletoe induced cytotoxicity in tumor cells, in relation to classic cytostatic therapy. VA ethanolic extract was administered alone and combined with doxorubicin (chloride), in Swiss female mice previously intraperitoneally (i.p.) inoculated with Ehrlich tumor cells (1×10 6 /animal), that consequently developed Ehrlich ascites carcinoma (EAC). The administered doses were of 50 mg/kg in the 1 st , 3 rd and 6th day for the VA extract, respectively of 2.5 mg/kg in the 1 st and 6 th day for doxorubicin, after tumor cell implantation. Fourteen days after, all mice were euthanized, ascites of the EAC were collected in order to analyze the tumor proliferation parameters, as well as blood samples, in order to evaluate the antioxidant status in plasma. Tumor development was associated with increased activity of plasma enzymes; classic doxorubicin therapy not only prevents the accumulation of ascitic fluid, but as well, significantly reduces the activity of plasma antioxidant enzymes. Furthermore, in association with VA extract, the protective effect is improved. Oxidative changes in Ehrlich tumor cells consisted in decreased catalase activity and amplified xanthine oxidase and peroxidase activities.
BMC Complementary and Alternative Medicine, 2014
Background: Given the importance of complementary and alternative medicine (CAM) to cancer patients, there is an increasing need to learn more about possible interactions between CAM and anticancer drugs. Mistletoe (Viscum album L.) belongs to the medicinal herbs that are used as supportive care during chemotherapy. In the in vitro study presented here the effect of standardized mistletoe preparations on the cytostatic and cytotoxic activity of several common conventional chemotherapeutic drugs was investigated using different cancer cell lines. Methods: Human breast carcinoma cell lines HCC1937 and HCC1143 were treated with doxorubicin hydrochloride, pancreas adenocarcinoma cell line PA-TU-8902 with gemcitabine hydrochloride, prostate carcinoma cell line DU145 with docetaxel and mitoxantrone hydrochloride and lung carcinoma cell line NCI-H460 was treated with docetaxel and cisplatin. Each dose of the respective chemotherapeutic drug was combined with Viscum album extract (VAE) in clinically relevant concentrations and proliferation and apoptosis were measured.
Postępy Higieny i Medycyny Doświadczalnej
Introduction Mistletoe has been used alone or as a complementary therapy in the treatment of different diseases for years. In this study, the antitumoral effect of mistletoe fruit extract on Ehrlich ascites tumor (EAT) cells was evaluated. Materials and Methods EAT cells from preformed stock mice were transferred to culture dishes containing 5-fluorouracil (5-FU) and mistletoe extracts at different doses (100, 200, 400, and 800 μg/ml). These cells were incubated at 37 °C in an environment with 95% humidity and 5% CO2. At the end of the incubations, the apoptosis status of the cells, cell cycle, mitochondrial membrane potential, and proliferation status with the argyrophilic (Ag) nucleolar organizer region staining (NORs) method were evaluated. Results As a result, it was observed that the mistletoe fruit extract and 5-FU induce apoptosis of EAT cells. It was concluded that the 5-FU substance arrests the cell cycle at the G0/G1 stage, while the mistletoe arrests the cell cycle at the...
Cell cycle arrest and apoptosis induction by methanolic leaves extracts of four Annonaceae plants
BMC Complementary and Alternative Medicine
Background: Uvaria longipes (Craib) L.L.Zhou, Y.C.F.Su & R.M.K.Saunders, Artabotrys burmanicus A.DC, Marsypopetalum modestum (Pierre) B.Xue & R.M.K.Saunders and Dasymaschalon sp. have been used for traditional medicine to treat cancer-like symptoms in some ethnic groups of Thailand and Laos. Methods: We evaluated the anti-cancer activity of these Annonaceae plants against several human cancer cell lines. The apoptosis induction was detected by Annexin/propidium iodide (PI) staining. Phytochemical screening was tested by standard protocols and bioactive compounds were determined by HPLC. Results: The crude extracts from leaves of U. longipes, Dasymaschalon sp., A. burmanicus, and M. modestum showed particular effects that were found to vary depending on the cancer cell line, suggesting that the effect was in a cell-type specific manner. Interestingly, the induction of apoptotic cell death was prominent by the leaves-derived crude extract of M. modestum. This crude was, therefore, subjected to cell cycle analysis by PI staining. Results showed that this crude extract arrested cell cycle and increased the percentage of cells in the SubG1 phase in some cancer cell lines. The phytochemical screening tests indicated that all crude extracts contained tannins and flavonoids. HPLC of flavonoids using standards identified rutin as an active compound in U. longipes and Dasymaschalon sp., whereas quercetin was found in U. longipes and M. modestum. Conclusions: These crude extracts provide a new source for rutin and quercetin, which might be capable of inducing cancer cell apoptotic death in a cell-type specific manner. This suggests, by analyzing the major bioactive compounds, the potential use of these crudes for chemotherapy in the future.
Herbal medicine as inducers of apoptosis in cancer treatment
Cancer is uncontrolled growth of abnormal cells in the body. Nowadays, cancer is considered as a human tragedy and one of the most prevalent diseases in the wide, and its mortality resulting from cancer is being increased. It seems necessary to identify new strategies to prevent and treat such a deadly disease. Control survival and death of cancerous cell are important strategies in the management and therapy of cancer. Anticancer agents should kill the cancerous cell with the minimal side effect on normal cells that is possible through the induction of apoptosis. Apoptosis is known as programmed cell death in both normal and damaged tissues. This process includes some morphologically changes in cells such as rapid condensation and budding of the cell, formation of membrane-enclosed apoptotic bodies with well-preserved organelles. Induction of apoptosis is one of the most important markers of cytotoxic antitumor agents. Some natural compounds including plants induce apoptotic pathways that are blocked in cancer cells through various mechanisms in cancer cells. Multiple surveys reported that people with cancer commonly use herbs or herbal products. Vinca Alkaloids, Texans, podo phyllotoxin, Camptothecins have been clinically used as Plant derived anticancer agents. The present review summarizes the literature published so far regarding herbal medicine used as inducers of apoptosis in cancer.