Anti-cancer activities of metal-based complexes by regulating the VEGF/VEGFR2 signaling pathway and apoptosis-related factors Bcl-2, Bax, and caspase-9 to inhibit angiogenesis and induce apoptosis

Qin, Xiuying; Wang, Ya-Nan; Liu, Han-Fu; Luo, Zhaohui; Zhang, Pei-Lu; Huang, Lifang; Liu, Meirong

doi:10.1039/c9mt00248k

Cited by 22 publications

(10 citation statements)

References 26 publications

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“…Copper is indispensable in the angiogenesis process, the administration of copper sequestering agents as an antitumor approach is under evaluation [5][6][7]. During the angiogenesis process, copper translocates from intracellular to extracellular space [55].…”

Section: Discussionmentioning

confidence: 99%

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The Ionophoric Activity of a Pro-Apoptotic VEGF165 Fragment on HUVEC Cells

Zimbone

Santoro

Mendola

et al. 2020

IJMS

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Copper plays an important role as a regulator in many pathologies involving the angiogenesis process. In cancerogenesis, tumor progression, and angiogenic diseases, copper homeostasis is altered. Although many details in the pathways involved are still unknown, some copper-specific ligands have been successfully used as therapeutic agents. Copper-binding peptides able to modulate angiogenesis represent a possible way to value new drugs. We previously reported that a fragment (VEGF73-101) of vascular endothelial growth factor (VEGF165), a potent angiogenic, induced an apoptotic effect on human umbilical vein endothelial cells. The aim of this study was to investigate the putative copper ionophoric activity of VEGF73-101, as well as establish a relationship between the structure of the peptide fragment and the cytotoxic activity in the presence of copper(II) ions. Here, we studied the stoichiometry and the conformation of the VEGF73-101/Cu(II) complexes and some of its mutated peptides by electrospray ionization mass spectrometry and circular dichroism spectroscopy. Furthermore, we evaluated the effect of all peptides in the absence and presence of copper ions by cell viability and cytofuorimetric assays. The obtained results suggest that VEGF73-101 could be considered an interesting candidate in the development of new molecules with ionophoric properties as agents in antiangiogenic therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

“…Recently, a study regarding the evaluation of novel copper-based complexes was conducted. It showed remarkable activities, both in vitro and in vivo, as a potential anti-cancer and anti-angiogenesis copper-containing drug [7].…”

Section: Introductionmentioning

confidence: 99%

The Ionophoric Activity of a Pro-Apoptotic VEGF165 Fragment on HUVEC Cells

Zimbone

Santoro

Mendola

et al. 2020

IJMS

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“…It was reported that low VEGF levels downregulated the antiapoptotic factor B‐cell lymphoma‐2 (Bcl‐2), 21 but upregulated the pro‐apoptotic factor BCL2‐associated X (Bax) 22 . The expression levels of apoptosis‐related proteins (caspase‐3, caspase‐8, caspase‐9, Bax, Bcl‐2 and VEGF) were detected via immunofluorescence analysis to investigate the antitumour mechanism of SNP.…”

Section: Resultsmentioning

confidence: 99%

Novel polysaccharide extracted from Sipunculus nudus inhibits HepG2 tumour growth in vivo by enhancing immune function and inducing tumour cell apoptosis

Deng-yuan

et al. 2021

J Cellular Molecular Medi

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A novel polysaccharide was extracted from Sipunculus nudus (SNP). The molecular weight (MW) of SNP was determined to be 9223 Da by high‐performance gel permeation chromatography analyses, and the structure of the SNP repeat units was determined to be →3,4‐β‐D‐GlcpNAC (1→ and →4) ‐α‐D‐Glcp (1→ in the ratio of 15:1; →2) ‐α ‐D‐Galp ‐ (1→ as a side chain; and β‐D‐Galp‐(1→ and α‐ D‐Glcp ‐ (1→ as end groups by GC‐MS analysis and NMR assays. The effect of SNP on hepatoma HepG2‐bearing mice was analysed to verify its potential in the clinical treatment of liver cancer. A total of 90 male athymic nu/nu mice were divided into therapeutic and preventive groups and fed with different amounts of SNP. The antitumour effect of SNP on HepG2‐bearing mice and mechanism of such were studied by analysing the tumour size, spleen index, thymus index, immune factors in the blood, tumour apoptosis factors, etc. The results suggest that SNP not only increased the index of immune organs in the body, but also enhanced the secretion of immune factors, including interleukin‐2, interferon gamma and tumour necrosis factor‐alpha in the serum. SNP induced the apoptosis of tumour cells via the mitochondrial apoptosis pathway, which upregulated caspase‐3, caspase‐8, caspase‐9 and BCL2‐associated X, but downregulated B‐cell lymphoma‐2 and vascular endothelial growth factor protein expression. In conclusion, SNP inhibited tumour growth by enhancing immune function and inducing tumour cell apoptosis in HepG2‐bearing mice. Therefore, SNP may be further investigated as a promising candidate for future antitumour drugs.

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“…Caspase9 can be activated in the mitochondrial apoptotic pathway and becomes its active form cleaved-caspase9, which plays an important role in the execution of apoptosis. 34 Studies have shown that PUFA promotes the apoptosis of colorectal cancer cells by inhibiting the expression of Bcl-2 and promoting the activation of caspase9. 35 In this study, we found that Omega-3PUFA inhibits the expression of Bcl-2 in colorectal cancer in vitro and in vivo, and promotes cleaved-caspase9 expression.…”

Section: Discussionmentioning

confidence: 99%

<p>Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling</p>

Huang

Chun-an

Cai

et al. 2020

OTT

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Background: Omega 3 polyunsaturated fatty acid (Omega-3PUFA) is one of the essential nutrients for human body involved in intracellular metabolic regulation and cell signaling. Previous studies have shown that Omega-3PUFA is involved in the pathogenesis of digestive system tumors, including colorectal cancer (CRC), however, the effects of Omega-3PUFA on CRC has not been fully elucidated. In the current study, we evaluated whether Omega-3PUFA can alleviate N-methyl-N-nitrosourea(MNU) induced CRC in a rat model and illustrated the potential mechanism. Methods: The effects of Omga-3PUFA on MNU-induced colorectal cancer in rats were analyzed by in vivo experiments. The viability, apoptosis, colony formation and invasion of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry, clone formation assay and transwell invasion assay. The expression of apoptosis-related proteins in CRC cells treated with Omga-3PUFA was detected by Western blotting. Finally, after adding PI3K activator, the viability, apoptosis and protein expression of CRC cells treated with Omga-3PUFA were detected by CCK8, flow cytometry and Western blotting. Results: Our results showed that Omega-3PUFA attenuated MNU-induced CRC in rats and inhibited AKT/Bcl-2 signaling in rats. In addition, Omega-3PUFA inhibited CRC cell proliferation and induces CRC cell apoptosis. Moreover, Omega-3PUFA inhibited CRC cell colony formation and invasion, and inhibited PI3K/AKT/Bcl-2 signaling in CRC cells. Furthermore, The effects of Omega-3PUFA on cell proliferation and apoptosis were inhibited by blocking PI3K/AKT signaling. Conclusion: Omega-3PUFA can attenuate MNU-induced colorectal cancer in rats by blocking PI3K/AKT/Bcl-2 signaling, which suggests that Omega-3PUFA may be a potent agent for CRC treatment.

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Anti-cancer activities of metal-based complexes by regulating the VEGF/VEGFR2 signaling pathway and apoptosis-related factors Bcl-2, Bax, and caspase-9 to inhibit angiogenesis and induce apoptosis

Abstract: Copper-based complexes exhibited multiple anti-cancer functions by regulating the expressions of Bcl-2, Bax, and caspase-9 and activating the VEGF/VEGFR2 signaling pathway.

Cited by 22 publications

References 26 publications

The Ionophoric Activity of a Pro-Apoptotic VEGF165 Fragment on HUVEC Cells

The Ionophoric Activity of a Pro-Apoptotic VEGF165 Fragment on HUVEC Cells

Novel polysaccharide extracted from Sipunculus nudus inhibits HepG2 tumour growth in vivo by enhancing immune function and inducing tumour cell apoptosis

<p>Omega-3PUFA Attenuates MNU-Induced Colorectal Cancer in Rats by Blocking PI3K/AKT/Bcl-2 Signaling</p>

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