Modulation of glycolysis and lipogenesis by novel PI3K selective molecule represses tumor angiogenesis and decreases colorectal cancer growth.

Autor: Hussain A; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Qazi AK; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Mupparapu N; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Guru SK; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Kumar A; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Sharma PR; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Singh SK; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Singh P; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Dar MJ; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Bharate SB; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Zargar MA; Department of Biochemistry, University of Kashmir, Srinagar, 190006, India., Ahmed QN; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Bhushan S; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Vishwakarma RA; Medicinal Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India., Hamid A; Cancer Pharmacology Division, CSIR-Indian Institute of Integrative Medicine, Jammu, 180001, India. Electronic address: ahdar@iiim.ac.in.
Jazyk: angličtina
Zdroj: Cancer letters [Cancer Lett] 2016 May 01; Vol. 374 (2), pp. 250-60. Date of Electronic Publication: 2016 Feb 23.
DOI: 10.1016/j.canlet.2016.02.030
Abstrakt: Phosphatidylinositol 3-kinase (PI3K) pathway drives cancer progression through direct regulation of most oncogenic properties. Here, we report that PI3K pathway signaling up-regulates cancer cell proliferation, metastasis and angiogenesis through modulation of cancer metabolism. These oncogenic metabolic processes were disrupted, by a novel PI3K inhibitor, 3-Dihydro-2-(naphthalene-1-yl) quinazolin-4(1H)-one (DHNQ) in colon cancer cells. DHNQ inhibited the Warburg effect and lipid synthesis by reducing gene expression of glycolytic and lipogenesis regulatory enzymes. This downregulation at gene level by DHNQ inhibited metabolic flux to repress proliferation, migration and invasion characteristics of colon cancer. Furthermore, the metabolic attenuation caused repression of in vitro/in vivo angiogenesis providing new insights in PI3K regulated angiogenesis via metabolic alterations. Our results suggest that multifaceted targeting of oncogenic metabolism by their upstream PI3K regulatory signaling may be an effective cancer treatment approach.
(Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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