Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGF-VEGFR2 signaling pathway

Fu, Zhongping; Xiao, Chen; Guan, Shengwen; Yan, Yanju; Lin, Huan Xin; Hua, Zichun

doi:10.18632/oncotarget.3625

Cited by 89 publications

(45 citation statements)

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“…Curcumin is a polyphenolic phytochemical compound, and it has multiple anti-cancer effects. For example, curcumin promotes apoptosis in several types of cancer cells [ 7 – 10 ] and inhibits migration [ 11 , 12 ] and angiogenesis [ 13 ]. Furthermore, curcumin enhances the cell death of cancer cells by anti-cancer drugs treatment, including TRAIL [ 14 – 16 ], 5-fluorouracil and gemcitabine [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

mTORC1/2 inhibitor and curcumin induce apoptosis through lysosomal membrane permeabilization-mediated autophagy

et al. 2018

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mTOR is an important regulator of cell growth and forms two complexes, mTORC1/2. In cancer, mTOR signaling is highly activated, and the regulation of this signaling, as an anti-cancer strategy, has been emphasized. However, PP242 (inhibitor of mTORC1 and mTORC2) alone did not induce human renal carcinoma cell death. In this study, we found that PP242 alone did not alter cell viability, but combined curcumin and PP242 treatment induced cell death. Combined PP242 and curcumin treatment induced Bax activation and decreased expression of Mcl-1 and Bcl-2. Furthermore, co-treatment with PP242 and curcumin-induced the downregulation of the Rictor (an mTORC2 complex protein) and Akt protein levels, and ectopic overexpression of Rictor or Akt inhibited PP242 plus curcumin induced cell death. Downregulation of Rictor increased cytosolic Ca2+ release from endoplasmic reticulum, which led to lysosomal damage in PP242 plus curcumin-treated cells. Furthermore, damaged lysosomes induced autophagy. Autophagy inhibitors markedly inhibited cell death. Finally, combined curcumin and PP242 treatment reduced tumor growth and induced cell death in xenograft models. Altogether, our results reveal that combined PP242 and curcumin treatment could induce autophagy-mediated cell death by reducing the expression of Rictor and Akt in renal carcinoma cells.

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Section: Introductionmentioning

confidence: 99%

mTORC1/2 inhibitor and curcumin induce apoptosis through lysosomal membrane permeabilization-mediated autophagy

et al. 2018

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“…Curcumin is one cancer chemopreventive compound; it is a polyphenolic phytochemical extracted from the rhizomes of the Curcuma longa plant. Curcumin could induce apoptosis in cancer cells [19] , [20] , [21] , [22] , [23] , [24] as well as inhibit VEGF and osteopontin-induced angiogenesis [25] , [26] . Furthermore, curcumin inhibits H 2 O 2 -induced invasion of pancreatic cancer [27] and blocks invasion of ovarian cancer spheroids into the mesothelial monolayers [28] .…”

Section: Introductionmentioning

confidence: 99%

NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin

Seo

Kim

et al. 2017

Redox Biology

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Thioridazine is known to have anti-tumor effects by inhibiting PI3K/Akt signaling, which is an important signaling pathway in cell survival. However, thioridazine alone does not induce apoptosis in head and neck squamous cell carcinoma (AMC-HN4), human breast carcinoma (MDA-MB231), and human glioma (U87MG) cells. Therefore, we investigated whether combined treatment with thioridazine and curcumin induces apoptosis. Combined treatment with thioridazine and curcumin markedly induced apoptosis in cancer cells without inducing apoptosis in human normal mesangial cells and human normal umbilical vein cells (EA.hy926). We found that combined treatment with thioridazine and curcumin had synergistic effects in AMC-HN4 cells. Among apoptosis-related proteins, thioridazine plus curcumin induced down-regulation of c-FLIP and Mcl-1 expression at the post-translational levels in a proteasome-dependent manner. Augmentation of proteasome activity was related to the up-regulation of proteasome subunit alpha 5 (PSMA5) expression in curcumin plus thioridazine-treated cells. Combined treatment with curcumin and thioridazine produced intracellular ROS in a NOX4-dependent manner, and ROS-mediated activation of Nrf2/ARE signaling played a critical role in the up-regulation of PSMA5 expression. Furthermore, ectopic expression of c-FLIP and Mcl-1 inhibited apoptosis in thioridazine and curcumin-treated cells. Therefore, we demonstrated that thioridazine plus curcumin induces proteasome activity by up-regulating PSMA5 expression via NOX4-mediated ROS production and that down-regulation of c-FLIP and Mcl-1 expression post-translationally is involved in apoptosis.

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“…Additionally, the JH-CX-DG formula may have an anti-tumor angiogenesis effect. An ELISA assay revealed that JH suppressed VEGF secretion from tumor cells and inhibited cancer angiogenesis [17]. Shen et al [18] found that DG could prevent cancer cell proliferation and cancer angiogenesis by inhibiting the PI3K/AKT/mTOR signaling pathway and downregulating the expression of HIF-1α and VEGF.…”

Section: Discussionmentioning

confidence: 99%

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

Liu¹,

Wang

2020

Preprint

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Background: Jianghuang (JH) is a popular ingredient in blood-regulating traditional Chinese Medicine (TCM) that could be effective for the treatment of various diseases. We demonstrate the compatibility laws and system pharmacological mechanisms of the key formula containing JH by leveraging data mining of bioinformatics databases.Material/Methods: The compatibility laws of blood-regulating formulae containing JH from the Chinese Traditional Medicine Formula Dictionary were analyzed using a generalized rule induction (GRI) algorithm implemented. The putative target gene and miRNA were retrieved via a combination of the Arrowsmith knowledge discovery tool and FunRich 3.1.3. System pharmacological mechanisms are traced by their protein-protein interaction (PPI) network, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was conducted using Uniprot, the Human Protein Atlas (HPA), STRING 11.0, and KOBAS 3.0.Results: We found that the JH-CX-DG formula (Ligusticum chuanxiong-Angelica sinensis) could represent a key formula containing JH in blood-regulating TCM formulae. The JH-CX-DG formula was observed to directly target AKT, TLR4, caspase-3, PI3K, mTOR, p38 MAPK, VEGF, iNOS, Nrf2, BDNF, NF-κB, Bcl-2, and Bax 13 targets and regulate targets through 13 miRNA. The PPI network and KEGG pathway enrichment analysis showed that the JH-CX-DG formula possess potential pharmacological effects including anti-inflammatory, improving microcirculation, and anti-tumor through the regulation of multiple pathways including PI3K/Akt, MAPK, Toll-like receptor, T cell receptor, EGFR, VEGFR, Apoptosis, HIF-1 (p < 0.05).Conclusion: The JH-CX-DG formula can exert beneficial pharmacological effects through multi-target and multi-pathway interactions. It can be effectively administered for the treatment of inflammatory diseases, microcirculation disorders, cardiovascular disease, and cancer. We found a new effective drug formula through analyzing the compatibility law and systemic pharmacological mechanism of JH. Our study provides a theoretical basis and directions for subsequent research on the JH-CX-DG formula.

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Curcumin inhibits angiogenesis and improves defective hematopoiesis induced by tumor-derived VEGF in tumor model through modulating VEGF-VEGFR2 signaling pathway

Cited by 89 publications

References 50 publications

mTORC1/2 inhibitor and curcumin induce apoptosis through lysosomal membrane permeabilization-mediated autophagy

mTORC1/2 inhibitor and curcumin induce apoptosis through lysosomal membrane permeabilization-mediated autophagy

NOX4-mediated ROS production induces apoptotic cell death via down-regulation of c-FLIP and Mcl-1 expression in combined treatment with thioridazine and curcumin

System Pharmacological Mechanism and Compatibility Laws of Jianghuang from Traditional Chinese Medicine In Blood-Regulating Formulae

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