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1. |
In Vivo January-February 2009 vol. 23 no. 1 63-68 |
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A Mastic Gum Extract Induces Suppression of Growth of Human Colorectal Tumor Xenografts in Immunodeficient Mice |
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KONSTANTINOS DIMAS1, SOPHIA HATZIANTONIOU2, JAMES H. WYCHE3 and PANAYOTIS PANTAZIS |
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1 Laboratory of Pharmacology-Pharmacotechnology, Foundation for Biomedical Research of the Academy of Athens
2 School of Pharmacy, Department of Pharmacological Technology, University of Athens, Greece
3 Oklahoma University Cancer Institute, University of Oklahoma Health Sciences Center, Department of Biochemistry and Molecular Biology, Oklahoma City, OK, U.S.A. |
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Abstract
Background: We recently reported that ethanol and hexane extracts of the plant product, mastic gum (MG), contain constituents which can induce p53- and p21-independent G1-phase arrest followed by apoptosis of human HCT116 colon cancer cells in vitro. Herein, we extended these studies to investigate the in vivo anticancer activity of the hexane extract of MG (He-MG) against human colon tumor. The in vivo anticancer activity of He-MG was assessed in a human colon cancer/immunodeficient mouse model.
Materials and Methods: Control and HCT116 tumor bearing SCID mice were injected intraperitoneally with He-MG at different administration schedules and doses ranging from 100 to 220 mg/kg body weight and tumor growth (size) was monitored.
Results: He-MG administered at a dose of 200 mg/kg administered daily for 4 consecutive days (followed by 3 days without treatment) inhibited tumor growth by approximately 35% in the absence of toxicity (side-effects) after 35 days.
Conclusion: He-MG was found to possess antitumor activity against human colorectal cancer under the experimental conditions of this study. The extent of suppression and toxicity by a specific He-MG dose depends on the schedule of administration.
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2. |
Phytomedicine 2005 Jan-Feb;19(1):93 - 102. |
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Antiproliferative activity and induction of apoptosis in human colon cancer cells treated in vitro with constituents of a product derived from Pistacia lentiscus L. var. chia. |
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K.V. Balana, J. Princea, Z. Hana, K. Dimasb, M. Cladarasc, J.H. Wychea, N.M. Sitarasd and P. Pantazisa, b, |
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a Department of Biology, University of Miami, Coral Gables, Miami, FL, USA
b Laboratory of Pharmacology–Pharmacotechnology, Foundation for Biomedical Research, Academy of Athens, Greece
c School of Biology, Aristotle University of Thessaloniki, Greece
d Department of Pharmacology, Medical School, University of Athens, Greece |
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Abstract
In this report, we demonstrate that a 50% ethanol extract of the plant-derived product, Chios mastic gum (CMG), contains compounds which inhibit proliferation and induce death of HCT116 human colon cancer cells in vitro. CMG-treatment induces cell arrest at G1, detachment of the cells from the substrate, activation of pro-caspases-8, -9 and -3, and causes several morphological changes typical of apoptosis in cell organelles. These events, furthermore, are time- and dose-dependent, but p53- and p21-independent. Apoptosis induction by CMG is not inhibited in HCT116 cell clones expressing high levels of the anti-apoptotic protein, Bcl-2, or dominant-negative FADD, thereby indicating that CMG induces cell death via a yet-to-be identified pathway, unrelated to the death receptor- and mitochondrion-dependent pathways. The findings presented here suggest that CMG (a) induces an anoikis form of cell death in HCT116 colon cancer cells that includes events associated with caspase-dependent pathways; and (b) might be developed into a chemotherapeutic agent for the treatment of human colon and other cancers.
Keywords: Chios mastic gum; Colon cancer cells; Apoptosis; Pistacia lentiscus L. var. chia |
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3. |
In Vivo. 2005 Jan-Feb;19(1):93 - 102. |
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Induction of apoptosis in human colon cancer HCT116 cells treated with an extract of the plant product, Chios mastic gum. |
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Balan KV, Demetzos C, Prince J, Dimas K, Cladaras M, Han Z, Wyche JH, Pantazis P. |
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Department of Biology, University of Miami, Coral Gables, Miami, FL 33146, USA. |
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Abstract
A hexane extract of the plant product Chios mastic gum (He-CMG) is demonstrated to kill human colon cancer cells in vitro via the process of anoikis. Specifically, the sequence of events includes He-CMG-induced GI-arrest of the cells, detachment of the cells from the substrate and subsequent apoptosis. Anoikis is dependent on the concentration and duration of treatment with He-CMG. Presence of the pan-caspase inhibitor, Z-VAD-fmk, did not prevent cell detachment, but it did prevent apoptosis of the detached cells indicating that the process of cell detachment, but not apoptosis, is independent of caspase activation. He-CMG-induced apoptosis is associated with activation of the initiator caspases-8, and -9 and the effector caspase-3. Caspases are activated in cells at a relatively long time after detachment, and caspase-3 activation may require caspase-8 or caspase-9 activation, as determined by using HCT116 isogenic clones impaired in apoptosis mechanisms that involve these two caspases. Finally, electron microscopy observations indicated a time-dependent appearance of morphological features both typical and non-typical of apoptosis in cells treated with He-CMG for various periods of time. Taken together, the results demonstrated that He-CMG induces apoptosis in HCT116 cells and, therefore, further in vivo and in vitro studies of the anticancer activities of this plant product are warranted. |
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4. |
Cancer Volume 106, Issue 12, Pages 2547 - 2555. |
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Gum mastic inhibits the expression and function of the androgen receptor in prostate cancer cells |
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Mei-Lan He, M.D. 1, Hui-Qing Yuan, Ph.D. 2, An-Li Jiang, M.D. 2, Ai Yu Gong, M.Sc. 3, Wei-Wen Chen, M.D. 2, Peng-Ju Zhang, M.D. 2, Charles Y. F. Young, Ph.D. 3 *, Jian-Ye Zhang, Ph.D. 2 * |
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1 Institute of Cancer Research, Life Science School, Tongji University, Shanghai, People's Republic of China
2 Institute of Biochemistry and Molecular Biology, Medical College, Shandong University, Jinan, People's Republic of China
3 Department of Urology, Mayo Clinic College of Medicine, Mayo Clinic/Foundation, Rochester, Minnesota |
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Abstract
Accumulating evidence suggests that the androgen receptor (AR) may play an important role in the development and progression of prostate cancer. To find new, useful compounds that effectively may attenuate the function of AR in prostate cancer cells, the authors investigated the effect of gum mastic, a natural resin, on AR activity. An androgen-responsive prostate cancer cell line LNCaP was used as a model for this study. Gene transfer, reverse transcriptase-polymerase chain reaction analysis, electrophoretic mobility shift assay, and Western blot analysis were used to test the effect of gum mastic on the expression and function of the AR. To demonstrate the inhibitory effect of gum mastic on the function of the AR, the expression of androgen- regulated genes, including prostate-specific antigen (PSA), human kallikrein 2 (hK2), and NKX3.1 were measured. In addition, transient transfection assays with the PSA promoter and the AR promoter also were used to test the effects of mastic. The results showed that gum mastic inhibited the expression of the AR at the transcriptional level, resulting in the down-regulation of both AR messenger RNA and protein levels. Therefore, the function of the AR was inhibited, as reflected by the reduced expression of NKX3.1 and PSA and by androgen-stimulated growth. Because gum mastic exhibited a strong in vitro potency to attenuate the expression and function of the AR, further investigation will be required to determine whether this naturally occurring substance has in vivo potency to inhibit prostate cancer development. |
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5. |
Acta Pharmacologica Sinica (2007) 28, 446–452; doi:10.1111/j.1745-7254.2007.00536.x |
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Mechanisms of antiprostate cancer by gum mastic: NF-B signal as target |
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Mei-lan He2, Ang Li2, Chun-su Xu2, Shun-li Wang3, Meng-jie Zhang2, Hua Gu2, Yao-qin Yang3 and Hui-hong Tao3 |
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2 Institute of Cancer Research, Life Science and Technology School, Tongji University, Shanghai 200092, China
3 Cellular Morphology Center, Medical School, Tongji University, Shanghai 200092, China |
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Abstract
Aim: To study the effect of gum mastic, a natural resin, on the proliferation of androgen-independent prostate cancer PC-3 cells, and further investigate the mechanisms involved in this regulatory system, taking nuclear factor B (NF-B) signal as the target.
Methods: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and a flow cytometer were used to detect the effect of gum mastic on the proliferation of PC-3 cells. Then, reporter gene assay, RT-PCR, and Western blotting were carried out to study the effects of gum mastic on the NF-B protein level and the NF-B signal pathway. The expression of genes involved in the NF-B signal pathway, including cyclin D1, inhibitors of BS (IB), and phosphorylated Akt (p-AKT), were measured. In addition, transient transfection assays with the 5 NF-B consensus sequence promoter was also used to test the effects of gum mastic.
Results: Gum mastic inhibited PC-3 cell growth and blocked the PC-3 cell cycle in the G1 phase. Gum mastic also suppressed NF-B activity in the PC-3 cells. The expression of cyclin D1, a crucial cell cycle regulator and an NF-B downstream target gene, was reduced as well. Moreover, gum mastic decreased the p-AKT protein level and increased the IB protein level.
Conclusion: Gum mastic inhibited the proliferation and blocked the cell cycle progression in PC-3 cells by suppressing NF-B activity and the NF-B signal pathway.
Keywords: gum mastic, prostate cancer, NF-B signal |
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6. |
Acta Pharmacologica Sinica (2007) 28, 567–572; doi:10.1111/j.1745-7254.2007.00535.x |
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Gum mastic increases maspin expression in prostate cancer cells |
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Mei-lan He2,3,6, Wei-wen Chen2,6, Peng-ju Zhang2, An-li Jiang2, Wei Fan4, Hui-qing Yuan2, Wen-wen Liu2 and Jian-ye Zhang2 |
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2 Department of Biochemistry, Medical School, Shandong University, Ji-nan 250012, China
3 Institute of Cancer Research, Life Science and Technology School, Tongji University, Shanghai 200092, China
4 Gastric Intestine Department, Affiliated Qi-Lu Hospital, Shandong University, Ji-nan 250012, China
6 These two authors are equally contributed. |
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Abstract
Aim: To study whether gum mastic, a natural resin, can regulate maspin expression in prostate cancer cells, and further investigate the mechanisms involved in this regulatory system.
Methods: RT-PCR and Western blotting were used to detect maspin expression at the transcriptional and translational levels. Reporter gene assay was used to investigate the effect of gum mastic on the maspin promoter. The binding activity of negative androgen-responsive element (ARE) and positive Sp1 element in the maspin promoter were studied by electrophoretic mobility shift assay.
Results: Gum mastic induced maspin mRNA and protein expression, and the maspin promoter activity was enhanced with gum mastic treatment. Finally, gum mastic inhibited the ARE binding activity and increased the Sp1 binding activity in the maspin promoter.
Conclusion: Gum mastic enhances maspin promoter activity by suppressing ARE binding activity and enhancing Sp1 binding activity, and the increased activity in the maspin promoter finally leads to the up-regulation of both its mRNA and protein levels.
Keywords: gum mastic, maspin expression, ARE binding activity, Sp1 binding activity |
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7. |
Korean J Anat. 2009 Dec;42(4):245-256. |
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Chios Gum Mastic Induces Cell Cycle Arrest and Apoptosis in Human Osteosarcoma Cells. |
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Min JH, Kim DK, Kwak HH, Kim GC, Lee SE, Kim IR, Kim CH, Park BS. |
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Department of Oral Anatomy, School of Dentistry, Pusan National University, Yangsan, Korea.
Department of Dentistry, College of Medicine, Dong-A University, Busan, Korea. |
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Abstract
Chios gum mastic (CGM) is a resin produced from the stem and leaves of Pistiacia lentiscus L var chia, a plant which grows only on Chios Island in Greece. CGM has been used for many centuries as a dietary supplement and folk medicine for stomach and duodenal ulcers in many Mediterranean countries and is also known to induce cell cycle arrest and apoptosis in some cancer cells. This study was undertaken to investigate the alteration of the cell cycle and induction of apoptosis by CGM treatment on human osteosarcoma (HOS) cells. The viability and the growth inhibition of HOS cells were assessed by the MTT assay and clonogenic assay respectively. The hoechst staining, TUNEL assay and DNA electrophoresis were conducted to observe the HOS cells undergoing apoptosis. HOS cells were treated with CGM, and Western blotting, immunocytochemistry, confocal microscopy, FACScan flow cytometry, mitochondrial membrane potential change and proteasome activity were conducted. CGM treatment of HOS cells was found to result in a dose- and time-dependent decrease in cell viability, a dose-dependent inhibition of cell growth, and apoptotic cell death. Tested HOS cells also showed several lines of apoptotic manifestation and G1 arrest in cell cycle progression. In summary, this study clearly demonstrated that CGM induces G1 cell cycle arrest via the modulation of cell cycle-related proteins, and apoptosis via proteasome, mitochondrial and caspase cascades in HOS cells. Therefore, our data provide the possibility that a natural product, CGM could be considered as a novel therapeutic strategy for human osteosarcoma. |
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8. |
BMC Medical Genomics 2009, 2:68 doi:10.1186/1755-8794-2-68 |
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A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival |
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Panagiotis Moulos1†, Olga Papadodima1†, Aristotelis Chatziioannou1, Heleni Loutrari2*, Charis Roussos2 and Fragiskos N Kolisis1* |
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1 Metabolic Engineering and Bioinformatics Group, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48 Vasileos Constantinou ave. 11635, Athens, Greece
2 "G.P. Livanos and M. Simou Laboratories", Evangelismos Hospital, Department of Critical Care and Pulmonary Services, School of Medicine, University of Athens, 2 Ploutarchou st., 10676, Athens, Greece |
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Abstract
Background:Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level.
Methods:To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h). Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562). PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects.
Results:In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation) and NOD1 (down-regulation) indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar expression profile. Promoter analysis in a representative cluster revealed shared putative cis-elements suggesting a common regulatory transcription mechanism.
Conclusions:Present results provide novel evidence on the molecular basis of tumor growth inhibition mediated by mastic oil and set a rational basis for application of genomics and bioinformatic methodologies in the screening of natural compounds with potential cancer chemopreventive activities. |
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9. |
Cancers 2011, 3(1), 789-801; doi:10.3390/cancers3010789 |
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Mastic Oil Inhibits the Metastatic Phenotype of Mouse Lung Adenocarcinoma Cells |
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Heleni Loutrari 1,* , Sophia Magkouta 1 , Andreas Papapetropoulos 2 and Charis Roussos 1 |
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1 “G.P. Livanos and M. Simou Laboratories”, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, School of Medicine, University of Athens, 3 Ploutarchou Street, 10675 Athens, Greece
2 Laboratory of Molecular Pharmacology, Department of Pharmacy, University of Patras, 26504 Patras, Greece |
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Abstract
Mastic oil from Pistacia lentiscus variation chia, a natural combination of bioactive terpenes, has been shown to exert anti-tumor growth effects against a broad spectrum of cancers including mouse Lewis lung adenocarcinomas (LLC). However, no studies have addressed its anti-metastatic actions. In this study, we showed that treatment of LLC cells with mastic oil within a range of non-toxic concentrations (0.01–0.04% v/v): (a) abrogated their Matrigel invasion and migration capabilities in transwell assays; (b) reduced the levels of secreted MMP-2; (c) restricted phorbol ester-induced actin remodeling and (d) limited the length of neo-vessel networks in tumor microenvironment in the model of chick embryo chorioallantoic membrane. Moreover, exposure of LLC and endothelial cells to mastic oil impaired their adhesive interactions in a co-culture assay and reduced the expression of key adhesion molecules by endothelial cells upon their stimulation with tumor necrosis factor-alpha. Overall, this study provides novel evidence supporting a multipotent role for mastic oil in prevention of crucial processes related to cancer metastasis.
Keywords: lung cancer; prevention; mastic plant essential oil; invasion; motility; adhesion; angiogenesis
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10. |
Nutr Cancer. 2011 Nov;63(8):1174-84. Epub 2011 Nov 1. |
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Current evidence on the anticancer potential of chios mastic gum. |
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Giaginis C, Theocharis S. |
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a Department of Forensic Medicine and Toxicology, Medical School , University of Athens , Athens , Greece. |
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Abstract
Chios mastic gum derived from the plant Pistacia lentiscus L. variation chia has been shown to exert beneficial effects on a wide range of human disorders. The most comprehensive data so far have indicated that mastic gum provides protection against gastrointestinal malfunctions and bacterial infections. Substantial evidence has also suggested that mastic gum exhibits hepatoprotective and cardioprotective, antiinflammatory/antioxidant, and antiatherogenic properties. In the last decade, an increasing number of studies further evaluated the potential antiproliferative properties of mastic gum against several types of human neoplasia. The present review aims to summarize the current data concerning the anticancer activities of mastic gum and their major constituents, highlighting also the molecular mechanisms through which they exert anticancer function. Mastic gum constituents that belong to the chemical class of triterpenoids appear to be mainly responsible for its anticancer potential. Thus, a brief discussion is dedicated to the anticancer activity of synthetic and naturally occurring triterpenoid analogues with similar chemical structure to mastic gum constituents. Taking into consideration the available data so far, Chios mastic gum could be considered as a conglomeration of effective anticancer drugs.
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11. |
Asian Pac J Cancer Prev. 2011;12(7):1877-80. |
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Chios Mastic Gum Extracts as a Potent Antitumor Agent that Inhibits Growth and Induces Apoptosis of Oral Cancer Cells. |
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Li S, Cha IH, Nam W. |
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Department of Pathology, Yanbian University , Yanji City, |
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Abrtract
Purpose: The purpose was to investigate Chios mastic gum (CMG) extract as an
potential anti-tumor agent for oral squamous cell carcinoma in vitro. Methods: We
designed a study to examine the effects of CMG extracts on growth of oral
squamous cell carcinoma cell line, YD-10B and to determine whether the extracts
could induce apoptosis through the activation of caspase-3, using the common
chemotherapeutic agent Paclitaxel (Taxol, Bristol-Myers Squibb) as a control.
Results: MTT assay suggested that both CMG and Taxol inhibited the proliferation
of YD-10B cells in a time and dose dependent manner. Moreover, 10μg/mL of CMG and
50μg/mL of Taxol caused fragmentation of the genomic DNA at 24 hour. Finally,
10μg/mL of CMG and 50μg/mL of Taxol caused cleavage of procaspase-3 in western
blot analysis. Conclusions: These results suggest CMG' s potential as an
anti-tumor agent. |
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12. |
International Journal of Drug Delivery, Vol 3 Issue 3(2011); Page 481-491 |
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Formulation and evaluation of mastic gum as a compression coat for colonic delivery of 5-flurouracil |
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Mohamed Nasr, Ibrahim E. Saad |
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Department of pharmaceutics, faculty of pharmacy, Helwan University, Cairo, Egypt. |
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Abstract
Mastic gum has been reported to possess considerable anti-tumor activity against human colorectal cancer. The purpose of this work was to evaluate mastic gum in formulation of colon-specific 5-flurouracil delivery system for effective treatment of colorectal cancer. Compression coated tablets, containing 5-flurouracil in the core tablet coated with 200mg of different coating materials containing various proportions of mastic gum were evaluated for their 5-flurouracil in vitro release. The results indicated that the concentrations of mastic gum, sodium chloride as well as hydroxypropyl methyl cellulose (HPMC) in the coating materials significantly modify the drug release. The coating material (F6) consisted of 60% mastic gum, 15% sodium chloride and 25% HPMC is considered as a promising formula for achieving colon targeting of 5-flurouracil. Further, gamma-scintigraphic studies were carried out in healthy male volunteers to evaluate in vivo release of F6. The results showed that tablets remained intact in stomach and small intestine, however partial and complete release of the tracer occurred in the colon. The in-vitro antitumor activity of 5-flurouracil-mastic gum combination mixed in a ratio representing their concentrations in tablets coated with F6 was carried out against colon cancer cell line using MTT assay. The results revealed that 5-flurouracil-mastic gum mixture was more effective in arresting cell growth in comparison to that shown by 5-flurouracil or mastic alone. In conclusion, this new colonic drug delivery system is potentially useful for 5-fkyriyracuk colon targeting. However, clinical benefits of using mastic in formulation of 5-flurouracil colonic tablets need further evaluation.
Keywords: Mastic gum, 5-flurouracil, Compression coating, Colonic delivery. |
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13. |
NUTRITION AND CANCER, 55(1), 86–93 |
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Mastic Oil from Pistacia lentiscus var. chia Inhibits Growth and Survival of Human K562 Leukemia Cells and Attenuates Angiogenesis |
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Heleni Loutrari, Sophia Magkouta, Anastasia Pyriochou, Vasiliki Koika, Fragiskos N. Kolisis, Andreas Papapetropoulos, and Charis Roussos |
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EvangelismosHospital, Department of Critical Care and Pulmonary Services, Medical School, University of Athens, 10675 Athens, Greece. |
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Abstract
Mastic oil from Pistacia lentiscus var. chia, a natural plant extract traditionally used as a food additive, has been extensively studied for its antimicrobial activity attributed to the combination of its bioactive components. One of them, perillyl alcohol (POH), displays tumor chemopreventive, chemotherapeutic, and antiangiogenic properties. We investigated whether mastic oil would also suppress tumor cell growth and angiogenesis. We observed that mastic oil concentration and time dependently exerted an antiproliferative and proapoptotic effect on K562 human leukemia cells and inhibited the release of vascular endothelial growth factor (VEGF) from K562 and B16 mouse melanoma cells. Moreover, mastic oil caused a concentration-dependent inhibition of endothelial cell (EC) proliferation without affecting cell survival and a significant decrease of microvessel formation both in vitro and in vivo. Investigation of underlying mechanism(s) demonstrated that mastic oil reduced 1) in K562 cells the activation of extracellular signal. regulated kinases 1/2 (Erk1/2) known to control leukemia cell proliferation, survival, and VEGF secretion and 2) in EC the activation of RhoA, an essential regulator of neovessel organization. Overall, our results underscore that mastic oil, through its multiple effects on malignant cells and ECs, may be a useful natural dietary supplement for cancer prevention. |
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14. |
Acta Pharmacologica Sinica (2010) 31: 741–745; doi: 10.1038/aps.2010.54 |
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Gemcitabine combined with gum mastic causes potent growth inhibition and apoptosis of pancreatic cancer cells |
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Xin-yu Huang1,#, Hong-cheng Wang1,#, Zhou Yuan1, Ang Li2, Mei-lan He2, Kai-xing Ai1, Qi Zheng1 and Huan-long Qin1 |
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1 Department of Surgery, the Sixth People's Hospital, Shanghai Jiaotong University, Shanghai 200233, China
2 School of Life Science and Technology, Tongji University, Shanghai 200092, China
#These authors contributed equally to the article. |
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Abstract
Aim: To investigate the antiproliferative and apoptotic effects of gemcitabine combined with gum mastic and the underlying mechanisms in human pancreatic cancer cell lines.
Methods: Cell proliferation and apoptosis were examined using the methyl thiazolyl tetrazolium (MTT) assay and propidium iodine staining, respectively. The expression of Bcl-2, Bax, NF-κB p65 subunit, and IκBα protein was measured using Western blotting.
Results: Gemcitabine 0.01−100 μg/mL inhibited cell proliferation and induced apoptosis in both pancreatic cancer BxPC-3 and COLO 357 cells. Gum mastic 40 μg/mL significantly potentiated the antiproliferative and apoptotic effects of gemcitabine 10 μg/mL after 72-h treatment. When cells were treated with gemcitabine in combination with gum mastic, the IκBα level was increased, whereas NF-κB activation was blocked; the expression of Bax protein was substantially increased, but Bcl-2 protein was down-regulated.
Conclusion: Gemcitabine combined with gum mastic causes potent apoptosis in pancreatic cancer cells. The combination may be an effective therapeutic strategy for pancreatic cancer.
Keywords: gemcitabine; gum mastic; pancreatic cancer; apoptosis; NF-kappaB; Bcl-2; Bax |
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