Inhibition of phosphoinositide 3-kinase is associated with reduced angiogenesis and an altered expression of angiogenic markers in endothelioma cells

Mabeta, Peaceful Lucy

doi:10.1016/j.biopha.2014.03.017

Cited by 5 publications

(4 citation statements)

References 29 publications

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“…These findings highlight the close relation between EGFR and VEGF inhibition and downstream signal transduction via the PI3-K/AKT pathway. This is corroborated by in vitro experiments using PI3-K inhibitor LY294002 which interrupts the PI3-K/AKT pathway resulting in decreased VEGF expression 98 .…”

Section: Pi3-k/akt Signaling Pathway and Radiation Resistancementioning

confidence: 63%

Targeting the AKT pathway: Repositioning HIV protease inhibitors as radiosensitizers

Goda¹,

Pachpor²,

Basu³

et al. 2016

Indian J Med Res

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Cellular resistance in tumour cells to different therapeutic approaches has been a limiting factor in the curative treatment of cancer. Resistance to therapeutic radiation is a common phenomenon which significantly reduces treatment options and impacts survival. One of the mechanisms of acquiring resistance to ionizing radiation is the overexpression or activation of various oncogenes like the EGFR (epidermal growth factor receptor), RAS (rat sarcoma) oncogene or loss of PTEN (phosphatase and tensin homologue) which in turn activates the phosphatidyl inositol 3-kinase/protein kinase B (PI3-K)/AKT pathway responsible for radiation resistance in various tumours. Blocking the pathway enhances the radiation response both in vitro and in vivo. Due to the differential activation of this pathway (constitutively activated in tumour cells and not in the normal host cells), it is an excellent candidate target for molecular targeted therapy to enhance radiation sensitivity. In this regard, HIV protease inhibitors (HPIs) known to interfere with PI3-K/AKT signaling in tumour cells, have been shown to sensitize various tumour cells to radiation both in vitro and in vivo. As a result, HPIs are now being investigated as possible radiosensitizers along with various chemotherapeutic drugs. This review describes the mechanisms by which PI3-K/AKT pathway causes radioresistance and the role of HIV protease inhibitors especially nelfinavir as a potential candidate drug to target the AKT pathway for overcoming radioresistance and its use in various clinical trials for different malignancies.

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Section: Pi3-k/akt Signaling Pathway and Radiation Resistancementioning

confidence: 63%

Targeting the AKT pathway: Repositioning HIV protease inhibitors as radiosensitizers

Goda¹,

Pachpor²,

Basu³

et al. 2016

Indian J Med Res

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“…For instance, high levels of VEGF have been measured in the urine samples of patients with proliferating IH [ 1 ]. Also, previously, the inhibition of VEGF secretion was shown to correlate with reduced tumor cell growth in human and murine hemangioma cells [ 21 , 22 ]. Furthermore, targeting downstream effectors in the VEGF signaling pathway resulted in the diminished growth of endothelial cells isolated from the murine hemangiomas [ 23 , 24 ].…”

Section: Vascular Endothelial Growth Factormentioning

confidence: 89%

Oncosuppressors and Oncogenes: Role in Haemangioma Genesis and Potential for Therapeutic Targeting

Mabeta

2018

IJMS

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Genetic lesions in proto-oncogenes result in the perturbation of angiogenesis, the formation of neovessels from a pre-existing microvasculature. Similarly, the subversion of tumor suppressor genes promotes tumor vascularization. Excessive neovessel formation is associated with various neoplasms such as infantile hemangiomas (IH). Hemangiomas are the most common tumors in pediatric patients and at present have no definitive treatment. The pathogenesis of IH is not well understood; however, both vasculogenesis and angiogenesis are associated with hemangioma genesis. A number of factors that modulate angiogenesis and vasculogenesis have been shown to be dysregulated in IH. Several of the oncogenes and tumor suppressors linked to the promotion of angiogenesis are also altered in infantile hemangioma. In this review, the roles of oncogenes and tumor suppressor genes during neovascularization and hemangioma genesis are explored. In addition, the potential for targeting these genes in IH therapy is discussed.

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“…Three wells were analysed for each concentration. The percentage of viable cells was calculated as follows: viability (%) = [A570 (treated) − A570 (blank)]/[A570 (control) − A570 (blank)] × 100 [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Novel 2,3-Dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones: Synthesis and Biological Evaluation

2016

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Herein we describe the synthesis and evaluation of a series of novel 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones for in vitro cytotoxicity against three human cancer cell lines as well as for potential antimalarial activity against the chloroquine-sensitive strain 3D7 of Plasmodium falciparum. The title compounds were prepared via PdCl2-mediated endo-dig cyclization of 2-aryl-8-(arylethynyl)-6-bromo-2,3-dihydroquinazolin-4(1H)-ones. The latter were prepared, in turn, via initial Sonogashira cross-coupling of 2-amino-5-bromo-3-iodobenzamide with aryl acetylenes followed by boric acid-mediated cyclocondensation of the intermediate 2-amino-3-(arylethynyl)-5-bromobenzamides with benzaldehyde derivatives. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4a–k were evaluated for potential in vitro cytotoxicity against the breast (MCF-7), melanoma (B16) and endothelioma (sEnd.2) cell lines. All of the compounds except 4h and 4i were found to be inactive against the three cancer cell lines. Compound 4h substituted with a 4-methoxyphenyl and 4-fluorophenyl groups at the 3- and 5-positions was found to exhibit significant cytotoxicity against the three cancer cell lines. The presence of phenyl and 3-chlorophenyl groups at the 3- and 5-posiitons of the pyrroloquinazolinone 4i, on the other hand, resulted in significant cytotoxicity against vascular tumour endothelial cells (sEnd.2), but reduced activity against the melanoma (B16) and breast cancer (MCF-7) cells except at higher concentrations. The 2,3-dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones 4a–l were found to be inactive against the chloroquine sensitive 3D7 strain of Plasmodium falciparum.

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Inhibition of phosphoinositide 3-kinase is associated with reduced angiogenesis and an altered expression of angiogenic markers in endothelioma cells

Cited by 5 publications

References 29 publications

Targeting the AKT pathway: Repositioning HIV protease inhibitors as radiosensitizers

Targeting the AKT pathway: Repositioning HIV protease inhibitors as radiosensitizers

Oncosuppressors and Oncogenes: Role in Haemangioma Genesis and Potential for Therapeutic Targeting

Novel 2,3-Dihydro-1H-pyrrolo[3,2,1-ij]quinazolin-1-ones: Synthesis and Biological Evaluation

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