Tricin 4′-O-(erythro-β-guaiacylglyceryl) ether and tricin 4′-O-(threo-β-guaiacylglyceryl) ether isolated from Njavara (Oryza sativa L. var. Njavara), induce apoptosis in multiple tumor cells by mitochondrial pathway
Mohanlal S.,Indian National Institute for Interdisciplinary Science and Technology |
Maney S.K.,Integrated Cancer Research Programme |
Santhoshkumar T.R.,Integrated Cancer Research Programme |
Jayalekshmy A.,Indian National Institute for Interdisciplinary Science and Technology
Journal of Natural Medicines | Year: 2013
Njavara is an important medicinal rice variety of Kerala, India widely used in Ayurveda for the treatment of rheumatoid arthritis, paralysis, neurodegenerative diseases and in rejuvenation therapy. The study evaluated, for the first time, antitumor effects of the two rare flavonolignans, tricin 4′-O-(erythro-β-guaiacylglyceryl) ether (compound 1) and tricin 4′-O-(threo-β-guaiacylglyceryl) ether (compound 2), isolated from 'Njavara' black. Both the compounds induced apoptosis in three cancer cell lines colon adenocarcinoma cell line HCT 116, ovarian cancer cell line SKOV3 and breast cancer cell line MCF-7. Chromatin condensation in the three cancer cell lines by Hoechst staining showed >50 % of apoptosis by compounds 1 and 2 at concentration 40 and 30 μg/ml, respectively after 48 h. Further studies substantiated that both the compounds targeted cancer cells through mitochondrial membrane potential loss and subsequent chromatin condensation. Both compounds significantly increased the Annexin V binding thus confirming compounds 1 and 2 to be potential apoptotic agents. © 2012 The Japanese Society of Pharmacognosy and Springer Japan.
Jisha S.,Rajiv Gandhi Center for Biotechnology |
Sreeja S.,Integrated Cancer Research Programme |
Manjula S.,Rajiv Gandhi Center for Biotechnology
Indian Journal of Medical Research | Year: 2011
Background & objectives: The mature fruits of Solanum nigrum contains steroidal glycosides. These are often used as vegetable and there are evidences on tribal use of these fruits as an oral contraceptive. The present study was carried out to evaluate the estrogenic potential of S. nigrum fruits by in vitro and in vivo assays. Methods: Defatted methanol extract of dried S. nigrum fruits was column fractionated and the glycoside positive fractions pooled. Definite concentrations of the fraction were used for in vitro and in vivo assays. The effect on cell viability was analyzed in MCF-7 cell lines by MTT assay followed by in vitro evaluation of estrogenicity by hydroxy apatite (HAP) binding assay. The results were further evaluated in vivo by performing uterotrophic assay in ovariectomized mouse models. Results: At low concentration (40 μg/ml), SNGF induced a dose-dependent increase in MCF-7 cell proliferation, while higher extract concentrations (80-320 μg/ml) caused progressive cell growth inhibition. The competitive binding assay using 3H-E 2 suggests that this effect is mediated by estrogen receptor. Mouse uterotrophic assay revealed a classical uterotrophic response in ovariectomized mice in response to S. nigrum glycoside fraction (SNGF). SNGF at a dose of 100 mg/kg of body wt induced the maximum height of luminal epithelial cells which indicated an increase of 30.8 per cent over control (P<0.01) with a correlated increase in uterine wet wt (150% increase over control). Higher doses (250 and 500 mg/kg body wt) of SNGF did not induce any uterotrophic effect. Interpretation & conclusions: Our preliminary data demonstrate the hormone like activity of Solanum glycosides both in vitro and in vivo in mouse, which needs to be further explored to evaluate the possible mechanism and clinical implications.
Bhavya B.C.,Integrated Cancer Research Programme |
Indira D.,Integrated Cancer Research Programme |
Seervi M.,Integrated Cancer Research Programme |
Joseph J.,Integrated Cancer Research Programme |
And 4 more authors.
Advances in Experimental Medicine and Biology | Year: 2012
Endoplasmic reticulum (ER) plays a key role in the maintenance of properly folded proteins, intracellular calcium, modification and trafficking of secretary proteins, etc. Any functional disturbance in ER triggers programmed cell death if reestablishment of homeostasis is failed. Several studies suggest toward a unique ER-centered apoptotic signaling separate from the Bax and Bak-dependent intrinsic apoptosis signaling during ER stress. Here, we show that significant loss of mitochondrial network and fragmentation before cytochrome c release during ER stress initiates the death signaling. The use of Bax-EGFP cells expressing MitoDsRed established that the mitochondrial fragmentation event during ER stress is upstream of Bax activation and its translocation to mitochondria. Caspase inhibitors failed to alter the mitochondrial fragmentation induced by multiple ER stress inducing agents. However, Bcl-2 overexpression specifically at ER significantly prevented early mitochondrial fragmentation and cell death induced by ER stress than the wild type Bcl-2 expressing cells. Our studies suggest that an early caspase-independent mitochondrial fragmentation as an initiating event during ER stress-induced cell death that is under the regulation of Bcl-2 resident at the ER. © 2012 Springer Science+Business Media, LLC.
PubMed | Integrated Cancer Research Programme
Type: Journal Article | Journal: Medicinal chemistry (Shariqah (United Arab Emirates)) | Year: 2010
A range of isatin-thiazolidinone hybrid analogues were synthesized and their cytotoxicity was evaluated against several cancer cell lines in vitro. The acute toxicity studies in mice models revealed that these analogues possess low systemic toxicity and are safe up to 1600mg/Kg. Among the compounds synthesized, 5-(2-nitrobenzylidene)-2-(isatin-3-azino)-thiazolidin-4-one (CI) has been shown to be the most active, highly promising compound which induced S phase arrest in cell cycle in a time dependent manner. Our initial analysis indicate that incorporation of electron withdrawing group at ortho position of the ring favors over the meta and para positions for eliciting its cytostatic effect. Overall, the in vitro biological evaluation suggests that the growth inhibitory effect of CI is promising and can be studied further.