Costunolide inhibits osteosarcoma growth and metastasis via suppressing STAT3 signal pathway

Jin, Xinmeng; Wang, Congcong; Wang, Lei

doi:10.1016/j.biopha.2019.109659

Cited by 20 publications

(9 citation statements)

References 24 publications

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“…S1a). Moreover, a previous study reported that CTD suppresses metastasis at a lower concentration in osteosarcoma cells [39], which matches our migration and invasion assay findings (Fig. 2).…”

Section: Discussionsupporting

confidence: 92%

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo

Huang

Park

Zhang

et al. 2021

J Exp Clin Cancer Res

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Background Colorectal cancer (CRC) is a clinically challenging malignant tumor worldwide. As a natural product and sesquiterpene lactone, Costunolide (CTD) has been reported to possess anticancer activities. However, the regulation mechanism and precise target of this substance remain undiscovered in CRC. In this study, we found that CTD inhibited CRC cell proliferation in vitro and in vivo by targeting AKT. Methods Effects of CTD on colon cancer cell growth in vitro were evaluated in cell proliferation assays, migration and invasion, propidium iodide, and annexin V-staining analyses. Targets of CTD were identified utilizing phosphoprotein-specific antibody array; Costunolide-sepharose conjugated bead pull-down analysis and knockdown techniques. We investigated the underlying mechanisms of CTD by ubiquitination, immunofluorescence staining, and western blot assays. Cell-derived tumour xenografts (CDX) in nude mice and immunohistochemistry were used to assess anti-tumour effects of CTD in vivo. Results CTD suppressed the proliferation, anchorage-independent colony growth and epithelial-mesenchymal transformation (EMT) of CRC cells including HCT-15, HCT-116 and DLD1. Besides, the CTD also triggered cell apoptosis and cell cycle arrest at the G2/M phase. The CTD activates and induces p53 stability by inhibiting MDM2 ubiquitination via the suppression of AKT’s phosphorylation in vitro. The CTD suppresses cell growth in a p53-independent fashion manner; p53 activation may contribute to the anticancer activity of CTD via target AKT. Finally, the CTD decreased the volume of CDX tumors without of the body weight loss and reduced the expression of AKT-MDM2-p53 signaling pathway in xenograft tumors. Conclusions Our project has uncovered the mechanism underlying the biological activity of CTD in colon cancer and confirmed the AKT is a directly target of CTD. All of which These results revealed that CTD might be a new AKT inhibitor in colon cancer treatment, and CTD is worthy of further exploration in preclinical and clinical trials.

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Section: Discussionsupporting

confidence: 92%

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo

Huang

Park

Zhang

et al. 2021

J Exp Clin Cancer Res

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“…There are several recent publications describing in vivo costunolide (3) studies, such as the work by Jin et al [92] on costunolide's anticancer effect on osteosarcoma xenografted mice. Results showed a daily 20 mg/kg (b.w.)…”

Section: Biosynthesis Of Costunolide (mentioning

confidence: 99%

Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases

et al. 2020

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Sesquiterpene lactones, a vast range of terpenoids isolated from Asteraceae species, exhibit a broad spectrum of biological effects and several of them are already commercially available, such as artemisinin. Here the most recent and impactful results of in vivo, preclinical and clinical studies involving a selection of ten sesquiterpene lactones (alantolactone, arglabin, costunolide, cynaropicrin, helenalin, inuviscolide, lactucin, parthenolide, thapsigargin and tomentosin) are presented and discussed, along with some of their derivatives. In the authors’ opinion, these compounds have been neglected compared to others, although they could be of great use in developing important new pharmaceutical products. The selected sesquiterpenes show promising anticancer and anti-inflammatory effects, acting on various targets. Moreover, they exhibit antifungal, anxiolytic, analgesic, and antitrypanosomal activities. Several studies discussed here clearly show the potential that some of them have in combination therapy, as sensitizing agents to facilitate and enhance the action of drugs in clinical use. The derivatives show greater pharmacological value since they have better pharmacokinetics, stability, potency, and/or selectivity. All these natural terpenoids and their derivatives exhibit properties that invite further research by the scientific community.

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“…Costunolide (COST; Figure 1 A) is a naturally occurring sesquiterpene lactone isolated from several Compositae plants. Several notable biological activities have been attributed to COST, notably its anticancer efficacy against bone, breast and blood cancer [ 11 , 12 ]. COST was also reported to show several other bioactivities including antioxidant, anti-inflammatory, antiulcer, antidiabetic and neuroprotective properties [ 11 , 13 , 14 , 15 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis

Wen

Wang

et al. 2022

Molecules

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Doxorubicin (DXB) is one of the most commonly used anticancer agents for treating solid and hematological malignancies; however, DXB-induced cardiorenal toxicity presents a limiting factor to its clinical usefulness in cancer patients. Costunolide (COST) is a naturally occurring sesquiterpene lactone with excellent anti-inflammatory, antioxidant and antiapoptotic properties. This study evaluated the effect of COST on DXB-induced cardiorenal toxicity in rats. Rats were orally treated with COST for 4 weeks and received weekly 5 mg/kg doses of DXB for three weeks. Cardiorenal biochemical biomarkers, lipid profile, oxidative stress, inflammatory cytokines, histological and immunohistochemical analyses were evaluated. DXB-treated rats displayed significantly increased levels of lipid profiles, markers of cardiorenal dysfunction (aspartate aminotransferase, creatine kinase, lactate dehydrogenase, troponin T, blood urea nitrogen, uric acid and creatinine). In addition, DXB markedly upregulated cardiorenal malondialdehyde, tumor necrosis factor-α, interleukin-1β, interleukin-6 levels and decreased glutathione, superoxide dismutase and catalase activities. COST treatment significantly attenuated the aforementioned alterations induced by DXB. Furthermore, histopathological and immunohistochemical analyses revealed that COST ameliorated the histopathological features and reduced p53 and myeloperoxidase expression in the treated rats. These results suggest that COST exhibits cardiorenal protective effects against DXB-induced injury presumably via suppression of oxidative stress, inflammation and apoptosis.

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Costunolide inhibits osteosarcoma growth and metastasis via suppressing STAT3 signal pathway

Cited by 20 publications

References 24 publications

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo

Targeting AKT with costunolide suppresses the growth of colorectal cancer cells and induces apoptosis in vitro and in vivo

Applications of Sesquiterpene Lactones: A Review of Some Potential Success Cases

Cardiorenal Protective Effect of Costunolide against Doxorubicin-Induced Toxicity in Rats by Modulating Oxidative Stress, Inflammation and Apoptosis

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