Dataset Information

Growth inhibition of human colon carcinoma cells by sesquiterpenoids and tetralones of Zygogynum calothyrsum.

ABSTRACT: Bioassay-guided phytochemical investigation of Zygogynum calothyrsum using the human colon carcinoma cell lines COLO205 and KM12 led to the isolation of three new drimane-type sesquiterpenoids, 1?-p-hydroxy-E-cinnamoyldrimeninol (1), 1?-p-hydroxy-E-cinnamoyl-5?-hydroxydrimeninol (2), and methyl ether of 1?-p-hydroxy-E-cinnamoyl-12?-methoxydrimeninol (3). Also isolated was the known 1?-p-coumaroyloxypolygodial (4) together with two new tetralones, 3'-deoxyisozygolone A (5) and calothyrlone A (9), three known tetralones, isozygolone A (6), zygolone A (7), and 4'-O-methylzygolone A (8), and a known cinnamolide (10). Compounds 1, 7, and 8 demonstrated higher cytotoxicity against COLO205 (GI50 18, 17, and 11 ?M, respectively) and KM12 (GI50 14, 14, and 17 ?M, respectively) than the other compounds.

SUBMITTER: Devkota KP

PROVIDER: S-EPMC3719390 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Growth inhibition of human colon carcinoma cells by sesquiterpenoids and tetralones of Zygogynum calothyrsum.

Devkota Krishna P KP Covell David D Ransom Tanya T McMahon James B JB Beutler John A JA

Journal of natural products 20130321 4

Bioassay-guided phytochemical investigation of Zygogynum calothyrsum using the human colon carcinoma cell lines COLO205 and KM12 led to the isolation of three new drimane-type sesquiterpenoids, 1β-p-hydroxy-E-cinnamoyldrimeninol (1), 1β-p-hydroxy-E-cinnamoyl-5α-hydroxydrimeninol (2), and methyl ether of 1β-p-hydroxy-E-cinnamoyl-12α-methoxydrimeninol (3). Also isolated was the known 1β-p-coumaroyloxypolygodial (4) together with two new tetralones, 3'-deoxyisozygolone A (5) and calothyrlone A (9), ...[more]

PMID: 23517126

Similar Datasets

Project description:To determine the effects of RNAi-mediated inhibition of the growth hormone receptor (GHR) gene on tumors and colon cancer cells in vivo.Construction of a eukaryotic vector for human GHR expression, the pcDNA6.2-GW/EmGFP-small interfering RNAs (siRNAs)-GHR plasmid, was used to inhibit GHR expression. Thirty-six BALB/c nude mice were randomly divided into groups and treated with normal saline (NS), recombinant plasmid (G?), growth hormone (GH), 5-fluorouracil (FU), G?+FU or G?+FU+GH. Each nude mouse was subcutaneously inoculated with 1 × 10(7) human colon cancer SW480 cells; the nude mice were weighed before inoculation and on the 2(nd), 5(th), 8(th), 11(th), 14(th) and 17(th) day after inoculation. All nude mice were sacrificed after 17 d. Each subcutaneous tumor was removed and studied. Tumor volume was measured on the 5(th), 8(th), 11(th), 14(th) and 17(th) day after inoculation. The expression of GHR protein in the tumor tissue was detected by Western blotting analysis, and the differences in GHR mRNA expression in the tumor tissue were detected by real-time quantitative reverse transcription-polymerase chain reaction.Compared to the control group, the weights of the inoculated nude mice on the 17(th) day after inoculation were: G?: 21.60 ± 0.71 g, GH: 21.64 ± 0.45 g, FU: 18.94 ± 0.47 g, FU+G?: 19.40 ± 0.60 g, G?+FU+GH: 21.04 ± 0.78 g vs NS: 20.68 ± 0.66 g, P < 0.05; the tumor volumes after the subcutaneous inoculation were: G?: 9.71 ± 3.82 mm(3), FU: 11.54 ± 2.42 mm(3), FU+G?: 11.42 ± 1.11 mm(3), G?+FU+GH: 10.47 ± 1.02 mm(3) vs NS: 116.81 ± 10.61 mm(3), P < 0.05. Compared to the GH group, the tumor volumes were significantly decreased in the experimental groups. The GHR protein expression (G?: 0.39 ± 0.02, FU: 0.40 ± 0.02, FU+G?: 0.38 ± 0.01, G?+FU+GH: 0.39 ± 0.01 vs NS: 0.94 ± 0.02, P < 0.05) and the GHR mRNA expression (G?: 14.12 ± 0.10, FU: 15.15 ± 0.44, FU+G?: 16.46 ± 0.27, G?+FU+GH: 15.37 ± 0.57 vs NS: 12.63 ± 0.14, P < 0.05) were significantly decreased and increased, respectively, in the experimental groups.Inhibition of GHR in human colon cancer SW480 cells resulted in anti-tumor effects in nude mice.

Project description:BackgroundTGF? signaling has typically been associated with suppression of tumor initiation while the role it plays in metastasis is generally associated with progression of malignancy. However, we present evidence here for an anti-metastatic role of TGF? signaling.MethodsTo test the importance of TGF? signaling to cell survival and metastasis we compared human colon carcinoma cell lines that are either non-tumorigenic with TGF? response (FET), or tumorigenic with TGF? response (FET?) or tumorigenic with abrogated TGF? response via introduction of dominant negative TGF?RII (FET?/DN) and their ability to metastasize. Metastatic competency was assessed by orthotopic transplantation. Metastatic colony formation was assessed histologically and by imaging.ResultsAbrogation of TGF? signaling through introduction of a dominant negative TGF? receptor II (TGF?RII) in non-metastatic FET? human colon cancer cells permits metastasis to distal organs, but importantly does not reduce invasive behavior at the primary site. Loss of TGF? signaling in FET?-DN cells generated enhanced cell survival capabilities in response to cellular stress in vitro. We show that enhanced cellular survival is associated with increased AKT phosphorylation and cytoplasmic expression of inhibitor of apoptosis (IAP) family members (survivin and XIAP) that elicit a cytoprotective effect through inhibition of caspases in response to stress. To confirm that TGF? signaling is a metastasis suppressor, we rescued TGF? signaling in CBS metastatic colon cancer cells that had lost TGF? receptor expression due to epigenetic repression. Restoration of TGF? signaling resulted in the inhibition of metastatic colony formation in distal organs by these cells. These results indicate that TGF? signaling has an important role in the suppression of metastatic potential in tumors that have already progressed to the stage of an invasive carcinoma.ConclusionsThe observations presented here indicate a metastasis suppressor role for TGF? signaling in human colon cancer cells. This raises the concern that therapies targeting inhibition of TGF? signaling may be imprudent in some patient populations with residual TGF? tumor suppressor activity.

Dataset Information

Growth inhibition of human colon carcinoma cells by sesquiterpenoids and tetralones of Zygogynum calothyrsum.

Publications

Growth inhibition of human colon carcinoma cells by sesquiterpenoids and tetralones of Zygogynum calothyrsum.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets