Enterohepatic recirculation of bioactive ginger phytochemicals is associated with enhanced tumor growth-inhibitory activity of ginger extract Sushma R.Gundala†, Rao Mukkavilli1,†, Chunhua Yang†,Pooja Yadav2, Vibha Tandon2, Subrahmanyam Vangala1, Satya Prakash3 and Ritu Anej a*Department of Biology, Georgia State University, Atlanta, GA 30303, USA, 1Advinus Therapeutics, Bangalore, Karnataka 560058, India, 2Department of Chemistry, University of Delhi, Delhi 110007, India and 3Department of Biomedical Engineering, McGill University, Montreal, Quebec H3G 1Y6, Canada Abstract
Phytochemical complexity of plant foods confers health-promot-ing benefits including chemopreventive and anticancer effects. Isolating single constituents from complex foods may render them inactive, emphasizing the importance of preserving the natural composition of whole extracts. Recently, we demonstrated in vitrosynergy among the most abundant bioactive constituents of gin-ger extract (GE), viz., 6-gingerol (6G), 8-gingerol (8G), 10-gingerol (10G) and 6-shogaol (6S). However, no study has yet examined the in vivo collaboration among ginger phytochemicals or evaluated the importance, if any, of the natural ‘milieu’ preserved in whole extract. Here, we comparatively evaluated in vivo efficacy of GE with an artificial quasi-mixture (Mix) formulated by combining four most active ginger constituents at concentrations equivalent to those present in whole extract. Orally fed GE showed 2.4-fold higher tumor growth-inhibitory efficacy than Mix in human pros-tate tumor xenografts. Pharmacokinetic evaluations and bioavail-ability measurements addressed the efficacy differences between GE and Mix. Plasma concentration-time profiles revealed multiple peaking phenomenon for ginger constituents when they were fed as GE as opposed to Mix, indicating enterohepatic recirculation. Bioavailability of 6G, 8G, 10G and 6S was 1.6-, 1.1-, 2.5- and 3.4-fold higher, respectively, when dosed with GE compared with Mix. In addition, gingerol glucuronides were detected in feces upon intravenous administration confirming hepatobiliary elimination. These data ascribe the superior in vivo efficacy of GE to higher area under the concentration time curves, greater residence time and enhanced bioavailability, of ginger phytochemicals, when fed as a natural extract compared with artificial Mix, emphasizing the usefulness of consuming whole foods over single agents. ....... In conclusion, our study emphasizes the existence of a complex collaborative interplay among GE phytochemicals to confer maxi-mum therapeutic benefits due to its favorable absorption kinetics and bioavailability. Our observations of possible EHR of gingerols, when delivered in their natural matrix, are compelling and provide impetus to investigate and design futuristic combinations/dietary supplements for prostate cancer management Source : Journal Carcinogenesis Link to Full Article
Differential Control of Growth, Apoptotic Activity, and Gene Expression in Human Breast Cancer Cells by Extracts Derived from Medicinal Herbs Zingiber officinale Ayman I. Elkady,1,2 Osama A. Abuzinadah,1 Nabih A. Baeshen,1 and Tarek R. Rahmy1,31Biological
Sciences Department, Faculty of Sciences, King Abdulaziz University, P. O. Box 80203, Jeddah 21589, Saudi Arabia 2Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt 3Zoology Department, Faculty of Science, Suez Canal University, Ismailia, Egypt
Abstract The present study aimed to examine the antiproliferative potentiality of an extract derived from the medicinal plant ginger (Zingiber officinale) on growth of breast cancer cells. Ginger treatment suppressed the proliferation and colony formation in breast cancer cell lines, MCF-7 and MDA-MB-231. Meanwhile, it did not significantly affect viability of nontumorigenic normal mammary epithelial cell line (MCF-10A). Treatment of MCF-7 and MDA-MB-231 with ginger resulted in sequences of events marked by apoptosis, accompanied by loss of cell viability, chromatin condensation, DNA fragmentation, activation of caspase 3, and cleavage of poly(ADP-ribose) polymerase. At the molecular level, the apoptotic cell death mediated by ginger could be attributed in part to upregulation of Bax and downregulation of Bcl-2 proteins. Ginger treatment downregulated expression of prosurvival genes, such as NF-κB, Bcl-X, Mcl-1, and Survivin, and cell cycle-regulating proteins, including cyclin D1 and cyclin-dependent kinase-4 (CDK-4). On the other hand, it increased expression of CDK inhibitor, p21. It also inhibited the expression of the two prominent molecular targets of cancer, c-Myc and the human telomerase reverse transcriptase (hTERT). These findings suggested that the ginger may be a promising candidate for the treatment of breast carcinomas.
Source : Journal of Biomedicine and Biotechnology Volume 2012 (2012), Article ID 614356, 14 pages doi:10.1155/2012/614356 Link to Full Article
Phytochemicals, antioxidant properties and anticancer investigations of the different parts of several gingers species (Boesenbergia rotunda, Boesenbergia pulchella var attenuata and Boesenbergia armeniaca) Ling Jing Jing1, Maryati Mohamed2, Asmah Rahmat3 and Mohd Fadzelly Abu Bakar1*
1Laboratory of Natural Products, Institute for Tropical Biology and Conservation, Universiti Malaysia Sabah, Locked Bag No. 2073, 88999, Kota Kinabalu, Sabah, Malaysia. 2Faculty of Civil Engineering and Environment, Universiti Tun Hussein Onn Malaysia, 86400 Parit Raja, Batu Pahat, Johor, Malaysia. 3Department of Nutrition and Dietetics, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400, UPM, Serdang, Selangor, Malaysia.
Abstract Extracts (methanol) of the leaves, stem and rhizome of Boesenbergia species were studied for their phytochemical constituents, total phenolics and flavonoid contents, antioxidant as well as anticancer properties. The plants revealed the presence of polyphenols such as quercetin, kaempferol, rutin, naringin, hesperidin, caffeic acid, p-coumaric acid, ferulic acid, sinapic acid, chlorogenic acid, gallic acid, luteolin and diosmin by using High Performance Liquid Chromatographic (HPLC). It was indicated with significant composition of hesperidin and naringin in B. pulchella var attenuata (leaves and stem); quercetin and kaempferol in B. rotunda; luteolin in B. armeniaca. The results of antioxidant assessments conducted were similar to the trend of total phenolic and flavonoid contents: B. pulchella var attenuata> B. rotunda> B. armeniaca. In the cytotoxicity assay, B. rotunda showed the most prominent and promising result as anticancer medicinal plant. It showed positive antiproliferative effect against five cancer cell lines: ovarian (CaOV3), breast (MDA-MB-231 and MCF-7), cervical (HeLa) and colon (HT-29) cancer cell lines with 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay conducted. In addition, the rhizome of B. pulchella var attenuata and B. armeniaca shown positive result in cytotoxicity assay tested against breast cancer (MCF-7). Thus, the Boesenbergia species investigated would be a promising anticancer remedy for breast cancer.
Source : Journal of Medicinal Plants Research Vol. 4(1), pp. 027-032, 4 January, 2010 Link to Full Article
1'S-1'-Acetoxyeugenol acetate: a new chemotherapeutic natural compound against MCF-7 human breast cancer cells by Noor Hasima, Lionel In Lian Aun, Mohamad Nurul Azmi, Ahmad Nazif Aziz, Eswary Thirthagiri, Halijah Ibrahim, Khalijah Awang
Medicinal plants containing active natural compounds have been
used as an alternative treatment for cancer patients in many parts of
the world especially in Asia (Itharat et al. 2004). In this report, we
describe the cytotoxic and apoptotic properties of 1'S-1'-acetoxyeugenol
acetate (AEA), an analogue of 1'S-1'-acetoxychavicol acetate (ACA),
isolated from the Malaysian ethno-medicinal plant Alpinia conchigera
Griff (Zingiberaceae) on human breast cancer cells. Data from MTT cell
viability assays indicated that AEA induced both time- and
dose-dependant cytotoxicity with an [IC.sub.50] value of 14.0 [mu]M
within 36 h of treatment on MCF-7 cells, but not in HMEC normal control
cells. Both annexin V-FITC/PI flow cytometric analysis and DNA
fragmentation assays confirmed that AEA induced cell death via
apoptosis. AEA was also found to induce cell cycle arrest in MCF-7 cells
at the [G.sub.0]/[G.sub.1] phase with no adverse cell cycle arrest
effects on HMEC normal control cells. It was concluded that AEA isolated
from the Malaysian tropical ginger represents a potential
chemotherapeutic agent against human breast cancer cells with higher
cytotoxicity potency than its analogue, ACA.
Alpinia conchigera, also known locally as 'lengkuas ranting', 'lengkuas
kecil', 'lengkuas padang', 'lengkuas getting' or 'chengkenam' (Janssen
and Scheffer 1985) is a herbaceous perennial, 2-5 feet tall, found in
eastern Bengal and southwards to Peninsular Malaysia and Sumatera
(Burkill 1966). It is used as a condiment in the northern states of
Peninsular Malaysia and occasionally in traditional medicine in the east
coast to treat fungal infections. In Thailand, the rhizomes are used in
traditional Thai medicine to relieve the gastro-intestinal disorders
and in the preparation of Thai food dishes (Matsuda et al. 2005).
Anti-tumour promoter activity in Malaysian ginger rhizobia used in traditional medicine S Vimala1, A W Norhanom2 and M Yadav3
1Medicinal Plant Division, Forest Research Institute Malaysia, Kepong, 52109, Kuala Lumpur
2Centre for Foundation Studies in Science;, University of Malaya, 50603, Kuala Lumpur, Malaysia
3Department of Genetics and Cellular Biology, University of Malaya, 50603, Kuala Lumpur, Malaysia
Received 15 January 1997; Revised 30 June 1998; Accepted 2 July 1998.
Abstract Zingiberaceae rhizomes commonly used in the Malaysian traditional medicine were screened for anti-tumour promoter activity using the short-term assay of inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) in Raji cells. The inhibition of TPA-induced EBV-EA was detected using the indirect immunofluorescence assay (IFA) and Western blot technique. The indirect IFA detected the expression/inhibition of EBV-EA-D (diffused EA antigen), whereas the Western blot technique detected the expression/inhibition of both EBV-EA-D and EA-R (restricted EA antigen). Seven rhizomes were found to possess inhibitory activity towards EBV activation, induced by TPA; they are: Curcuma domestica, C. xanthorrhiza, Kaempferia galanga, Zingiber cassumunar, Z. officinale, Z. officinale (red variety), and Z. zerumbet. A cytotoxicity assay was carried out to determine the toxicity of the Zingiberaceae rhizome extracts. The rhizome extracts that exhibited EBV activation inhibitory activity had no cytotoxicity effect in Raji cells. Therefore, the present study shows that several Zingiberaceae species used in Malaysian traditional medicine contain naturally occurring non-toxic compounds that inhibit the EBV activation, which, if further investigated, could contribute in the development of cancer prevention methods at the tumour-promoting stage.
LINK TO FULL ARTICLE Inhibition of Tumor Promotion in SENCAR Mouse Skin by Ethanol Extract ofZingiber officinale Rhizome1 Santosh K. Katiyar, Rajesh Agarwal, and Hasan MUkhtar
Depara@mentof Dermatology, Skin Diseases Research Center, University Hospitals of Cleveland, Case Western Reserve University, Cleveland. Ohio 44106
Abstract There is considerable emphasis on Identifying potential chemopreventive agents present in food consumed by the human population. Ginger rhizome (Zingiber officinale), known commonly as ginger, Is consumed worldwide in cookeries as a spice and a flavoring agent. In prior in vitro studies, it has been shown that the water or organic solvent extract of ginger possesses antioxidative and antlinflammatory properties. In this study, we evaluated whether ethanol extract of ginger (GE) possesses anti-tumor.promoting effects In a mouse skin tumorigenesis model. Because skin tumor promoters induced epidermal ornithine decarboxylase (ODC), cyclooxygenase, and lipoxygenase activities, and edema and hyperplasia are conventionally used markers of skin tumor promotion, first,
we assessed the effect of GE on these parameters. Preapplication of GE onto the skin of SENCAR mice resulted in significant inhibition of 12-0-tetradecanoylphorbol-13-acetate (TPA)-caused induction of epidermal ODC, cyclooxygenase, and lipoxygenase activities and ODC mRNA expression In a dose-dependent manner. Preapplication of GE to mouse skin also afforded significant inhibition of TPA-caused epidermal edema (56%) and hyperplasia (44%). In long-term tumor studies, topical application of GE 30 mm prior to that of each TPA application to 7,12-dimethylbenz(a)anthracene-initiated SENCAR mice resulted in a highly significant protection against skin tumor incidence and Its subsequent multiplicity. The animals pretreated with GE showed substantially lower tumor body burdens compared with non-GE-treated controls. The results of our study,for the first time,provide clear evidence that GE possesses anti-skin tumor-promoting effects, and that the mechanism ofsuch effects may involve inhibition of tumor promoter-caused cellular, biochemical, and molecular changes in mouse skin.
188th Medical Group, Wright-Patterson AFB, Ohio, USA 2National Institutes of Health, National Human Genome Research Institute, Cancer Genetics Branch, USA 3Department of Family Medicine, University of Michigan, Ann Arbor, MI, USA 4Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Michigan, Ann Arbor, MI, USA 5Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA
Abstract. Background Ginger (Zingiber officinale Rosc) is a natural dietary component with antioxidant and anticarcinogenic properties. The ginger component -gingerol has been shown to exert anti-inflammatory effects through mediation of NF-κB. NF-κB can be constitutively activated in epithelial ovarian cancer cells and may contribute towards increased transcription and translation of angiogenic factors. In the present study, we investigated the effect of ginger on tumor cell growth and modulation of angiogenic factors in ovarian cancer cells in vitro.
Conclusion Ginger inhibits growth and modulates secretion of angiogenic factors in ovarian cancer cells. The use of dietary agents such as ginger may have potential in the treatment and prevention of ovarian cancer.