Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Villalobos-Ayala, Krystal; Rivera, Ivannie Ortiz; Alvarez, Ciara; Husain, Kazim; DeLoach, DeVon; Krystal, Gerald; Hibbs, Margaret L.; Jiang, Kun; Ghansah, Tomar

doi:10.3390/cancers12123631

Cited by 21 publications

(34 citation statements)

References 61 publications

(102 reference statements)

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“…Although cancer cells can escape immune-surveillance by tuning down autophagy, phytochemical agents with immunogenic and autophagy-promoting properties may enhance antitumor immunity by inducing autophagic cell death [ 54 ]. For apigenin, luteolin, and chrysoeriol, immunogenic and autophagy-promoting properties have already been reported ( Supplementary Table S6 ) [ 32 , 33 , 38 , 39 , 59 ]. In addition, we previously found that treatment with another purified TTE constituent (Thalassiolin B) fully mimicked ROS production and tumor regression by polyphenolic fraction treatment in a xenograft colorectal cancer model [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Marine Seagrass Extract of Thalassia testudinum Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways

et al. 2021

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Marine plants have become an inexhaustible reservoir of new phytopharmaceuticals for cancer treatment. We demonstrate in vitro/in vivo antitumor efficacy of a standardized polyphenol extract from the marine angiosperm Thalassia testudinum (TTE) in colon tumor cell lines (RKO, SW480, and CT26) and a syngeneic allograft murine colorectal cancer model. MTT assays revealed a dose-dependent decrease of cell viability of RKO, CT26, and SW480 cells upon TTE treatment with IC50 values of, respectively, 175, 115, and 60 μg/mL. Furthermore, TTE significantly prevented basal and bFGF-induced angiogenesis in the chicken chorioallantoic membrane angiogenesis assay. In addition, TTE suppressed bFGF-induced migration of endothelial cells in a wound closure assay. Finally, TTE treatment abrogated CT26 colorectal cancer growth and increased overall organism survival in a syngeneic murine allograft model. Corresponding transcriptome profiling and pathway analysis allowed for the identification of the mechanism of action for the antitumor effects of TTE. In line with our in vitro/in vivo results, TTE treatment triggers ATF4-P53-NFκB specific gene expression and autophagy stress pathways. This results in suppression of colon cancer cell growth, cell motility, and angiogenesis pathways in vitro and in addition promotes antitumor immunogenic cell death in vivo.

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Section: Discussionmentioning

confidence: 99%

Marine Seagrass Extract of Thalassia testudinum Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways

et al. 2021

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“…Further studies on the pelorol agonists ZPR-151 16 and AQX-435 17 would seem to be a logical starting point for this area. Pre-clinical studies clearly indicate a link between SHIP modulation and the growth and development of many cancers [ 185 , 186 ]. Armed with the structural information provided by x-ray crystallographers, medicinal chemistry studies can now be fully engaged to develop paralog selective potent inhibitors and agonists which can then be evaluated in tumor models.…”

Section: Ship Agonistsmentioning

confidence: 99%

Targeting SHIP1 and SHIP2 in Cancer

Pedicone

Meyer

Chisholm

et al. 2021

Cancers

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Membrane-anchored and soluble inositol phospholipid species are critical mediators of intracellular cell signaling cascades. Alterations in their normal production or degradation are implicated in the pathology of a number of disorders including cancer and pro-inflammatory conditions. The SH2-containing 5’ inositol phosphatases, SHIP1 and SHIP2, play a fundamental role in these processes by depleting PI(3,4,5)P3, but also by producing PI(3,4)P2 at the inner leaflet of the plasma membrane. With the intent of targeting SHIP1 or SHIP2 selectively, or both paralogs simultaneously, small molecule inhibitors and agonists have been developed and tested in vitro and in vivo over the last decade in various disease models. These studies have shown promising results in various pre-clinical models of disease including cancer and tumor immunotherapy. In this review the potential use of SHIP inhibitors in cancer is discussed with particular attention to the molecular structure, binding site and efficacy of these SHIP inhibitors.

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“…While PDK1, mTOR, TBK1 and MERTK are Akt-phosphorylating kinases, the lipid phosphatases such as phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and Src homology 2 domain-containing inositol-5-phosphatase (SHIP) can inhibit the phosphorylation of Akt by PI3K pathway [ 112 – 114 ]. Mechanistically, PTEN and SHIP convert PIP3 into PI(4,5)P2 and PI(3,4)P2, respectively.…”

Section: Mechanisms Of Akt Activation and Inactivationmentioning

confidence: 99%

Targeting Akt in cancer for precision therapy

et al. 2021

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Biomarkers-guided precision therapeutics has revolutionized the clinical development and administration of molecular-targeted anticancer agents. Tailored precision cancer therapy exhibits better response rate compared to unselective treatment. Protein kinases have critical roles in cell signaling, metabolism, proliferation, survival and migration. Aberrant activation of protein kinases is critical for tumor growth and progression. Hence, protein kinases are key targets for molecular targeted cancer therapy. The serine/threonine kinase Akt is frequently activated in various types of cancer. Activation of Akt promotes tumor progression and drug resistance. Since the first Akt inhibitor was reported in 2000, many Akt inhibitors have been developed and evaluated in either early or late stage of clinical trials, which take advantage of liquid biopsy and genomic or molecular profiling to realize personalized cancer therapy. Two inhibitors, capivasertib and ipatasertib, are being tested in phase III clinical trials for cancer therapy. Here, we highlight recent progress of Akt signaling pathway, review the up-to-date data from clinical studies of Akt inhibitors and discuss the potential biomarkers that may help personalized treatment of cancer with Akt inhibitors. In addition, we also discuss how Akt may confer the vulnerability of cancer cells to some kinds of anticancer agents.

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Apigenin Increases SHIP-1 Expression, Promotes Tumoricidal Macrophages and Anti-Tumor Immune Responses in Murine Pancreatic Cancer

Cited by 21 publications

References 61 publications

Marine Seagrass Extract of Thalassia testudinum Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways

Marine Seagrass Extract of Thalassia testudinum Suppresses Colorectal Tumor Growth, Motility and Angiogenesis by Autophagic Stress and Immunogenic Cell Death Pathways

Targeting SHIP1 and SHIP2 in Cancer

Targeting Akt in cancer for precision therapy

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