title: CCR5 blockage by maraviroc induces cytotoxic and apoptotic effects in colorectal cancer cells.
abstract: Alterations in the expression of C-C chemokine receptor type 5 (CCR5 or CD195) have been correlated with disease progression in different cancers. Recently, a few investigations have reported the blockage of this receptor by an antagonist (maraviroc) and its antineoplastic effects on tumor cell growth. However, little is known about the mechanistic reasons behind these antineoplastic effects of CCR5 blockage by maraviroc. In this study, we blocked the CCR5 receptor by maraviroc in SW480 and SW620 colorectal cancer cells to study the resulting changes in biological properties and related pathways. This blockage induced significantly reduced proliferation and a profound arrest in G1 phase of the cell cycle. Concomitantly, maraviroc caused significant signs of apoptosis at morphological level. Significant modulation of multiple apoptosis-relevant genes was also noticed at mRNA levels. In addition, we found remarkable increases in cleaved caspases at protein level. These modulations led us to propose a signaling pathway for the observed apoptotic effects. In conclusion, blocking the CCR5 by maraviroc induces significant cytotoxic and apoptotic effects in colorectal cancer cells. Thus, maraviroc can be considered a model compound, which may foster the development of further CCR5 antagonists to be used for the treatment of colorectal cancer.
authors.affiliation: Toxicology and Chemotherapy Unit, German Cancer Research Center, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
authors.forename: Asim
authors.initials: A
authors.lastname: Pervaiz
authors.forename: Shariq
authors.initials: S
authors.lastname: Ansari
authors.forename: Martin R
authors.initials: MR
authors.lastname: Berger
authors.forename: Hassan
authors.initials: H
authors.lastname: Adwan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D003510:Cyclohexanes / Q000494:pharmacology*; D016193:G1 Phase; D006801:Humans; D000077592:Maraviroc; D012333:RNA, Messenger / Q000235:genetics; D019713:Receptors, CCR5 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014230:Triazoles / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; C584933:CCR5 protein, human; D003510:Cyclohexanes; D012333:RNA, Messenger; D019713:Receptors, CCR5; D014230:Triazoles; D000077592:Maraviroc
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