Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

Vendramini–Costa, Débora Barbosa; Alcaide, Antonio Montero; Pelizzaro-Rocha, Karin Juliane; Talero, Elena; Ávila-Román, Javier; García‐Mauriño, Sofía; Pilli, Ronaldo Aloise; Carvalho, João Ernesto de; Motilva, Virginia

doi:10.1016/j.taap.2016.03.009

Cited by 22 publications

(24 citation statements)

References 59 publications

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“…Under homeostatic conditions, this mild stress induces an adaptive cytoprotection response (57,58). However, in tumor cells the basal levels of ROS are already increased, and as we have shown before, GTN further increases cellular ROS levels in tumor cells, likely overloading the antioxidant system, leading to apoptosis (23). In this study, we observed a protective effect of GTN at both the 30 and 100 mg/kg doses, with a largely similar anti-inflammatory effect, as gauged by the decreases in pro-inflammatory cytokines.…”

Section: Discussionmentioning

confidence: 63%

“…In particular, inhibition of chronic inflammation, which precedes or accompanies tumor development, has recently come to light as an attractive option. Racemic GTN, a styryl lactone found in its R configuration in plants of the genus Goniothalamus, Annonaceae, has in vitro antiproliferative activity in human tumor cell lines via activation of apoptosis (18)(19)(20)23,38). GTN also presents general anti-inflammatory effects, without side effects (as seen with aspirin, for example) in the therapeutic doses (20,22,39).…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies performed by our group showed that racemic GTN presents gastroprotective effects, anti-inflammatory activity and inhibits the development of Ehrlich tumor (mammary adenocarcinoma) in mice (19)(20)(21)(22). Recently, we showed that GTN induces apoptosis in HT-29 colon tumor cells, which was dependent on ROS generation and caspase activation (23). GTN is a small molecule that can be synthesized using a straightforward synthetic procedure and previous studies indicated its absence of side effects in vivo, highlighting GTN as a promising candidate for pre-clinical studies.…”

Section: Introductionmentioning

confidence: 93%

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Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Vendramini–Costa

Francescone

Posocco

et al. 2016

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The tumor microenvironment offers multiple targets for cancer therapy, including pro-tumorigenic inflammation. Natural compounds represent an enormous source of new anti-inflammatory and anticancer agents. We previously showed that the styryl lactone goniothalamin (GTN) has promising antiproliferative and anti-inflammatory activities. Because inflammation is a major driver of colorectal cancer (CRC), we therefore evaluated the therapeutic and preventive potentials of GTN in colitis, colitis-associated cancer (CAC) and spontaneous CRC. First, in a simplistic model of inflammation in vitro, GTN was able to inhibit cytokine production in bone marrow-derived macrophages induced by lipopolysaccharide. Next, in dextran sulfate sodium (DSS) induced-colitis model, mice treated with GTN displayed restored tissue architecture, increased cell proliferation in the colonic crypts and reduced epithelial damage. Moreover, colon tissue from GTN-treated mice had significantly less expression of the inflammatory genes interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), S100A9, interleukin 23A (IL-23A), IL-22 and IL-17A. In the azoxymethane/DSS model of CAC, GTN reduced tumor multiplicity, load and size. Additionally, GTN suppressed production of IL-6, IL-17 and TNF-α in tumor tissue, as well as abrogated stromal immune cell activation and nuclear translocation of NF-κB. Finally, in a tamoxifen inducible model of sporadic CRC, GTN-treated mice had significantly fewer tumors and decreased levels of IL-17A, IL-6, S100A9 and TNF-α protein within the tumors. These results suggest that GTN possesses anti-inflammatory and antitumor activities and represents a preventive and therapeutic agent modulating the inflammatory environment in the colon during colitis as well as CAC and CRC development.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 93%

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Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Vendramini–Costa

Francescone

Posocco

et al. 2016

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“…Recent research group has demonstrated that goniothalamin showed cytotoxicity and apoptosis induction in various tumor cell lines, H1299 (non-small cell lung cancer) (16), HepG2 (human hepatoblastoma) (17), SK-BR-3 (human breast cancer) (13), A549 (lung carcinoma) (18), HL60 (promyelocytic leukemia) (19,20), SGC7901 (stomach cancer) (21), HT29 (colon cancer) (22,23), HeLa (cervical cancer) (24), and MDA-MB231 (invasive breast cancer) (25). However, the study of goniothalamin in MM have not yet been reported.…”

Section: Discussionmentioning

confidence: 99%

Mechanism of apoptosis induction associated with ERK1/2 upregulation via goniothalamin in melanoma cells

et al. 2018

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Abstract. The present study aimed to investigate the effect of goniothalamin on apoptosis induction in the A375 melanoma cell line. Melanoma is a type of skin cancer with increased prevalence and no potential standard treatment. Goniothalamin is a plant, bioactive styrly-lactone, which has various bioactivities including anti-microbial, anti-inflammatory and anti-cancer. Apoptosis induction by goniothalamin has been studied in numerous cancer cell lines, however not in the melanoma cell line A375. The results of the MTT assay demonstrated that goniothalamin induced anti-proliferation in a dose dependent manner. Hoechst staining assay demonstrated that goniothalamin induced chromatin condensation and apoptotic bodies in A375 treated cells, and JC-1 staining revealed that goniothalamin induced mitochondrial membrane dysfunction in A375 cells. In addition, goniothalamin decreased the level of anti-apoptotic proteins myeloid cell leukemia 1, B cell lymphoma (Bcl)-2 and Bcl-extra large, whereas it increased the level of pro-apoptotic proteins, Bcl-2 Associated X, apoptosis regulator, t-BID and Bim in A375 treated cells. In addition, goniothalamin also increased active caspase-9, -7 and cleaved-poly (ADP-ribose) polymerase expression in A375 treated cells. Furthermore, phosphorylated (p)-pyruvate dehydrogenase kinase (PDK) 1 (Ser241) and p-RAC-alpha serine/threonine-protein kinase (Akt; Ser473) were decreased, however c-Jun and p-extracellular signal-regulated kinase (ERK)1/2 were increased upon goniothalamin treatment. These results suggest that goniothalamin has an effect, as anti-proliferation and apoptosis induction in A375 cells were associated with upregulated p-ERK1/2, c-Jun and downregulated p-PDK1 (Ser241), p-Akt (Ser473) in A375 cells. Therefore, goniothalamin may be a potential candidate for anti-cancer drug development for melanoma treatment.

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“…The styryl lactone Goniothalamin (GTN) is a secondary metabolite found in plants from Goniothalamus genus . It was first isolated in 1972 and after that, several studies have characterized different GTN properties, such as anti‐proliferative and cytotoxic against cancer cells, anti‐inflammatory, pro‐apoptotic, and gastroprotective .…”

Section: Introductionmentioning

confidence: 99%

Goniothalamin and Celecoxib Effects During Aging: Targeting Pro‐Inflammatory Mediators in Chemoprevention of Prostatic Disorders

et al. 2017

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Goniothalamin prevents the development of chemically induced and spontaneous colitis in rodents and induces apoptosis in the HT-29 human colon tumor cell line

Cited by 22 publications

References 59 publications

Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Anti-inflammatory natural product goniothalamin reduces colitis-associated and sporadic colorectal tumorigenesis

Mechanism of apoptosis induction associated with ERK1/2 upregulation via goniothalamin in melanoma cells

Goniothalamin and Celecoxib Effects During Aging: Targeting Pro‐Inflammatory Mediators in Chemoprevention of Prostatic Disorders

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