Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation

Thirusangu, Prabhu; Vigneshwaran, V.; Avin, B.R. Vijay; Heer, Rakesh; Vikas, H.M.; Prabhakar, B.T.

doi:10.1016/j.bbrc.2017.01.067

Cited by 30 publications

(21 citation statements)

References 24 publications

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“…Moreover, DLL potentially reduced the peroxidized lipids in tumour mice (Fig. 4h), which have been highly implicated in tumour angiogenesis and release of HIF-1a into the tumour microenvironment [48,49]. Together, this evidence highlights DLL's potential in neovascularization inhibition.…”

Section: Discussionmentioning

confidence: 79%

Immunomodulatory glc/man-directedDolichos lablablectin (DLL) evokes anti-tumour responsein vivoby counteracting angiogenic gene expressions

Vigneshwaran

Thirusangu

Avin

et al. 2017

Clinical and Experimental Immunology

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Neovascularization and jeopardized immunity has been critically emphasized for the establishment of malignant progression. Lectins are the diverse class of carbohydrate interacting proteins, having great potential as immunopotentiating and anti-cancer agents. The present investigation sought to demonstrate the anti-proliferative activity of Dolichos lablab lectin (DLL) encompassing immunomodulatory attributes. DLL specific to glucose and mannose carbohydrate moieties has been purified to homogeneity from the common dietary legume D. lablab. Results elucidated that DLL agglutinated blood cells non-specifically and displayed striking mitogenicity to human and murine lymphocytes in vitro with interleukin (IL)-2 production. The DLL-conditioned medium exerted cytotoxicity towards malignant cells and neoangiogenesis in vitro. Similarly, in-vivo anti-tumour investigation of DLL elucidated the regressed proliferation of ascitic and solid tumour cells, which was paralleled with blockade of tumour neovasculature. DLL-treated mice showed an up-regulated immunoregulatory cytokine IL-2 in contrast to severely declined levels in control mice. Mechanistic validation revealed that DLL has abrogated the microvessel formation by weakening the proangiogenic signals, specifically nuclear factor kappa B (NF-κB), hypoxia inducible factor 1α (HIF-1 α), matrix metalloproteinase (MMP)-2 and 9 and vascular endothelial growth factor (VEGF) in malignant cells leading to tumour regression. In summary, it is evident that the dietary lectin DLL potentially dampens the malignant establishment by mitigating neoangiogenesis and immune shutdown. For the first time, to our knowledge, this study illustrates the critical role of DLL as an immunostimulatory and anti-angiogenic molecule in cancer therapeutics.

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Section: Discussionmentioning

confidence: 79%

Immunomodulatory glc/man-directedDolichos lablablectin (DLL) evokes anti-tumour responsein vivoby counteracting angiogenic gene expressions

Vigneshwaran

Thirusangu

Avin

et al. 2017

Clinical and Experimental Immunology

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“…4E and F). In addition, the present study detected the effect of the scutellarein/RAGE axis on the activation of signals which have been reported to be under the regulation of scutellarein, including nuclear factor-κβ (32), PKc (33) and VEGF (34). The results revealed that scutellarein treatment significantly decreased the expression levels of p-p65, PKc and VEGF compared with the control group (P<0.05), whereas the expression levels of p-p65 and VEGF were neutralized when RAGE was overexpressed, while RAGE downregulation further decreased p-p65 and VEGF expression levels compared with the scutellarein group (P<0.05; Fig.…”

Section: Scutellarein Inhibits Cell Proliferation and Promotes Cell Amentioning

confidence: 70%

Scutellarein inhibits the development of colon cancer via CDC4‑mediated RAGE ubiquitination

Wang

Zhong

et al. 2020

Int J Mol Med

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Scutellarein has been identified to serve an anti-tumor function in human colon cancer, but the underlying mechanisms remain largely unclear. The present study further investigated the effect and mechanism of scutellarein, extracted from wild chrysanthemum, in the progression of colon cancer. MTT, clone formation, flow cytometry and tumor-bearing mice assays were used to detect cell viability, clone formation, apoptosis and tumorigenesis, respectively. Western blot and quantitative PcR assays were performed for protein and mRNA expression detection. The results revealed that, compared with the control group, scutellarein treatment significantly inhibited the viability and induced the apoptosis of colon cancer cells (P<0.05), with significant decreases in receptor for advanced glycosylation end products (RAGE) protein expression and stability and an increase in RAGE ubiquitination (P<0.05). However, the effects of scutellarein exerted in cell apoptosis and viability were rescued by RAGE overexpression, and accelerated by RAGE knockdown. Additionally, it was observed that scutellarein treatment induced a significant increase in the expression of cell division control protein 4 (cdc4) compared with the control group (P<0.05), which was then verified to interact with RAGE protein and mediate its ubiquitination. Overexpression of cdc4 inhibited colon cancer cell viability and promoted the apoptosis of SW480 and T84 cells, whereas this function was weakened when RAGE was overexpressed. Furthermore, CDC4 downregulation significantly neutralized scutellarein functions in promoting cell apoptosis and inhibiting cell viability and tumorigenesis in colon cancer cells compared with the scutellarein group (P<0.05). In conclusion, the present study revealed that scutellarein inhibited the development of colon cancer through upregulating cdc4-mediated RAGE ubiquitination.

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“…Experimental proofs suggest that scutellarein has an excellent potential in inhibiting the progress of tumors by modulating the sprouting neovasculature and 40 kDa DNA fragmentation factor-mediated cell death. 83 Scutellarein attenuates proliferation in the lung cancer A549 cell line through the epidermal growth factor receptor pathway by mediating ERK and NF-kB. The cell proliferation of A549 can be obviously suppressed by using 50 mM scutellarein in 24 h and/or 48 h of treatment.…”

Section: Anticancer Effects Of Scutellarein and Scutellarinmentioning

confidence: 97%

Polyphenols of Chinese skullcap roots: from chemical profiles to anticancer effects

et al. 2019

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Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation

Cited by 30 publications

References 24 publications

Immunomodulatory glc/man-directedDolichos lablablectin (DLL) evokes anti-tumour responsein vivoby counteracting angiogenic gene expressions

Immunomodulatory glc/man-directedDolichos lablablectin (DLL) evokes anti-tumour responsein vivoby counteracting angiogenic gene expressions

Scutellarein inhibits the development of colon cancer via CDC4‑mediated RAGE ubiquitination

Polyphenols of Chinese skullcap roots: from chemical profiles to anticancer effects

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