Isopimpinellin extends antiangiogenic effect through overexpression of miR-15b-5p and downregulating angiogenic stimulators

Author(s):  
Sambhavi Bhagavatheeswaran ◽  
Vinu Ramachandran ◽  
Sambantham Shanmugam ◽  
Anandan Balakrishnan
Processes ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 850
Author(s):  
Kristine Guran ◽  
Roxana Buzatu ◽  
Iulia Pinzaru ◽  
Madalina Boruga ◽  
Iasmina Marcovici ◽  
...  

Melissa officinalis is a medicinal herb with an extensive pharmacological profile that has been proven to have beneficial effects in oral and gastrointestinal disorders. However, the effects of this plant in oral, pharyngeal, and colorectal malignancies, types of cancer with an increased incidence in recent years, are less investigated. The present study aims to evaluate the pharmacological profile of a Melissa officinalis total extract for potential benefits in oral, pharynx and colorectal carcinoma. The LC-MS profile of MO total extract (MOte) indicated a rich content in polyphenols, data that support the potent antioxidant capacity exhibited and the antimicrobial activity against both Gram-negative and Gram-positive bacteria. In addition, MOte triggered a dose-dependent and selective decrease in the viability of tumor cells (tongue and pharynx squamous cell carcinomas, and colorectal adenocarcinoma), with the most significant effect being recorded at 100 µg/mL. At the same concentration, MOte exhibited an antiangiogenic effect by inhibiting the process of angiogenesis in ovo. Overall, our findings support the potential benefits of Melissa officinalis leaf total extract as a valuable candidate for the prophylaxis of oral, pharyngeal and colorectal neoplasms.


2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
A. P. Athira ◽  
A. Helen ◽  
K. Saja ◽  
P. Reddanna ◽  
P. R. Sudhakaran

Angiogenesis is a crucial step in the growth of cancer and its metastasis. It is regulated by several endogenous factors which may stimulate or inhibit the new blood vessel growth. Besides these endogenous factors, several exogenous factors including some natural compounds are known to modulate angiogenesis. Angiogenesis being a potential target for drugs against a number of pathological conditions, search for compounds from natural sources that can affect angiogenesis is of great interest. The objective of our present study was to understand the effect of chebulagic acid, a COX-LOX dual inhibitor isolated from the fruits ofTerminalia chebulaRetz., on angiogenesis. The model systems used were rat aortic rings and human umbilical vein endothelial cells. The results showed that chebulagic acid exerts an antiangiogenic effect. This was evidenced from decreased sprouting in rat aortic rings and decrease in biochemical markers in endothelial cells treated with chebulagic acid. It downregulated the production of CD31, E-selectin, and vascular endothelial growth factor in human umbilical vein endothelial cells in culture (HUVEC). Further studies to understand the molecular mechanism of action of chebulagic acid revealed that CA exerts its anti angiogenic effect by modulating VE cadherin-βcatenin signalling in human umbilical vein endothelial cells.


2021 ◽  
Vol 08 ◽  
Author(s):  
Mohammad Sako ◽  
Malek Zihlif ◽  
Fatma Afifi

Background: Angiogenesis is the formation of new blood vessels from pre-existing ones. It occurs in both physiological and pathological conditions. Objectives: We aimed to evaluate the antiangiogenic effect of Elaeagnus angustifolia L. water extract in vivo to determine any anti-proliferative effect of the extract on the A549 lung cancer cell line, and to investigate its effect on VEGF-A and FGF2 expression in the A549 cell line. Methods: Trypan blue exclusion test was implemented to establish any possible anti-proliferative effect of the extract. Then, Matrigel plug assay was performed on mice using the same cell line to test the antiangiogenic effect of the extract. Finally, A549 cells were treated with the extract at concentrations of 25, 12.5, and 6.25 µg/ml to investigate the changes in VEGF-A and FGF2 expression by RT-qPCR. Results: E. angustifolia extract did not exhibit a significant anti-proliferative effect against A549 cells. The extract at concentrations of 12.5 and 6.25 µg/ml demonstrated an inhibitory effect against the growth of new blood vessels by 75.63 and 45.26%, respectively. The extract did not affect the expression of VEGF-A and FGF2 in A549 cells. Conclusion: Our findings show that water extract of E. angustifolia possesses potent antiangiogenic activity, while neither exhibiting significant anti-proliferative effect nor affecting VEGF-A or FGF2 expression in the A459 cell line, suggesting either sole direct antiangiogenic effect, or both direct and indirect effects with paracrine suppression of other genes.


2021 ◽  
Vol 35 (3) ◽  
Author(s):  
Yusuke Ichiyama ◽  
Shumpei Obata ◽  
Yoshitsugu Saishin ◽  
Osamu Sawada ◽  
Masashi Kakinoki ◽  
...  

2010 ◽  
Vol 298 (6) ◽  
pp. G865-G877 ◽  
Author(s):  
Parvaneh Rafiee ◽  
David G. Binion ◽  
Michael Wellner ◽  
Behnaz Behmaram ◽  
Martin Floer ◽  
...  

Radiation therapy is an essential modality in the treatment of colorectal cancers. Radiation exerts an antiangiogenic effect on tumors, inhibiting endothelial proliferation and survival in the tumor microvasculature. However, damage from low levels of irradiation can induce a paradoxical effect, stimulating survival in endothelial cells. We used human intestinal microvascular endothelial cells (HIMEC) to define effects of radiation on these gut-specific endothelial cells. Low-level irradiation (1–5 Gy) activates NF-κB and the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is involved in cell cycle reentry and cell survival in HIMEC. A downstream target of PI3K/Akt is mammalian target of rapamycin (mTOR), which contributes to endothelial proliferation and angiogenesis. The aim of this study was to investigate the signaling molecules involved in the radiosensitizing effects of curcumin on HIMEC subjected to low levels of irradiation. We have demonstrated that exposure of HIMEC to low levels of irradiation induced Akt and mTOR phosphorylation, which was attenuated by curcumin, rapamycin, LY294002, and mTOR small interference RNA (siRNA). Activation of NF-κB by low levels of irradiation was inhibited by curcumin, SN-50, and mTOR siRNA. Curcumin also induced apoptosis by induction of caspase-3 cleavage in irradiated HIMEC. In conclusion, curcumin significantly inhibited NF-κB and attenuated the effect of irradiation-induced prosurvival signaling through the PI3K/Akt/mTOR and NF-κB pathways in these gut-specific endothelial cells. Curcumin may be a potential radiosensitizing agent for enhanced antiangiogenic effect in colorectal cancer radiation therapy.


2006 ◽  
Vol 66 (17) ◽  
pp. 8698-8706 ◽  
Author(s):  
Benjamin D. Zeitlin ◽  
Esther Joo ◽  
Zhihong Dong ◽  
Kristy Warner ◽  
Guoping Wang ◽  
...  

2013 ◽  
Vol 21 (9) ◽  
pp. 837-845 ◽  
Author(s):  
Silvia L. Fialho ◽  
Pedro A. F. Souza ◽  
Gustavo O. Fulgêncio ◽  
Murilo M. O. Miranda ◽  
Bruno G. Pereira ◽  
...  

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
M. Huylebrouck ◽  
S. Lv ◽  
J. Duerinck ◽  
A. Van Binst ◽  
I. Salmon ◽  
...  

Background. Bevacizumab (BEV), a humanized immunoglobulin G1 monoclonal antibody that inhibits VEGF has demonstrated activity against recurrent high-grade gliomas (HGG) in phase II clinical trials.Patients and Methods. Data were collected from patients with recurrent HGG who initiated treatment with BEV outside a clinical trial protocol at two Belgian university hospitals.Results. 19 patients (11 M/8 F) were administered a total of 138 cycles of BEV (median 4, range 1–31). Tumor response assessment by MRI was available for 15 patients; 2 complete responses and 3 partial responses for an objective response rate of 26% for the intent to treat population were observed on gadolinium-enhanced T1-weighted images; significant regressions on T2/FLAIR were documented in 10 out of 15 patients (67%). A reduced uptake on PET was documented in 3 out of 4 evaluable patients. The six-month progression-free survival was 21% (95% CI 2.7–39.5). Two patients had an ongoing tumor response and remained free from progression after 12 months of BEV treatment.Conclusions. The activity and tolerability of BEV were comparable to results from previous prospective phase II trials. Reduced uptake on PET suggests a metabolic response in addition to an antiangiogenic effect in some cases with favorable clinical outcome.


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