Umbelliprenin shows antitumor, antiangiogenesis, antimetastatic, anti‐inflammatory, and immunostimulatory activities in 4T1 tumor‐bearing Balb/c mice

Abstract

Umbelliprenin (UMB) has shown various pharmacological properties in vitro. We investigated the antineoplastic and immunostimulatory effects of UMB in 4T1 mammary-tumor-bearing mice. Two-hundred microliter of UMB (12.5 mg/ml) was intraperitoneally administrated to healthy and tumor-bearing female Balb/c mice for a period of 18 days. Data was analyzed using GraphPad Prism 5 software for Windows (version 5, La Jolla, CA). UMB caused a significant decrease in tumor size (P < 0.01). Serum interferon gamma (IFNγ) was augmented in both healthy and tumor-bearing animals (P < 0.01), and IL-4 declined in healthy animals (P < 0.01) treated with UMB. Expressions of Ki-67, VEGF, CD31, MMP2, MMP9, VCAM1, and NF-κB were significantly decreased in tumors from UMB-treated animals (P < 0.001), whereas E-Cadherin and TNFR1 expressions were markedly increased (P < 0.001). The rates of liver and lung metastases in UMB-administrated animals were smaller compared to the control. UMB can potently inhibit tumor growth, angiogenesis, metastasis, and inflammation and potentiate an antitumor immune response in vivo. However, further investigations are required to evaluate the UMB mechanisms of action in cancerous cells.

Coumarins fromMagydaris pastinaceaas inhibitors of the tumour-associated carbonic anhydrases IX and XII: isolation, biological studies and in silico evaluation

“…Umbelliprenin (15) showed moderate cytotoxicity against HeLa cells (IC 50 75 lM) and this result is in accord with other studies reporting the low cytotoxicity of the compound towards the breast cancer cell lines MCF and 4T1 50,51 . However, umbelliprenin was effective to inhibit tumour growth, angiogenesis and metastasis in mammary tumour-bearing mice when intraperitoneally administrated 52 . These data were confirmed by Zhang et al 53 , which provided evidence that umbelliprenin may inhibit the growth, invasion and migration of gastric cancer cells by targeting the Wnt signalling pathway, with little to no harm in the lung, heart and kidney.…”

Assessment of the Antitumor Potential of Umbelliprenin, a Naturally Occurring Sesquiterpene Coumarin

“…The studies on breast cancer cell line, i.e., MCF-7, showed increased cell death and decreased cell viability upon treatment with UMB in a dose dependent manner [51]. The IC50 values for UMB in different breast cancer cell lines varied in different studies ranging from 30-75 µM in a concentration dependent manner [48,65].…”

“…Studies using UMB as a potential antitumor agent (10 mg/mL) against colon cancer cells (DLD-1) showed reduced viability in a dose dependent manner [51]. IC50 values for UMB in human colon cancer cells (HT29) were noted to be 36.4 ± 1.6 and in mouse colon cancer cells (CT26) 51.4 ± 2.9 after 24 h of treatment [65]. UMB exhibited cytotoxic actions against invasive colon cancer cells (SW48), while non-invasive colon cancer cells (SW1116) showed enhanced proliferation when exposed to different concentrations of UMB [71].…”

Expression of Diverse Angiogenesis Factor in Different Stages of the 4T1 Tumor as a Mouse Model of Triple-Negative Breast Cancer

“…Various breast cancer models in mice have been developed previously, but each model has its own strength and limitations. 18,22,23 Even though the syngeneic models have some weakness points such as quick progression and metastasis, still, are the simplest models for research of tumor growth and metastasis. 7,24,25 Although we have been working on the production of this model for many years successfully, we have never fully comprehended this tumor in terms of these significant angiogenesis markers.…”