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In Vitro Antitumor Effects of AHR Ligands Aminoflavone (AFP 464) and Benzothiazole (5F 203) in Human Renal Carcinoma Cells
Author(s) -
Luzzani Gabriela A.,
Callero Mariana A.,
Kuruppu Anchala I.,
Trapani Valentina,
Flumian Carolina,
Todaro Laura,
Bradshaw Tracey D.,
Loaiza Perez Andrea I.
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.26114
Subject(s) - apoptosis , cancer research , signal transduction , cancer cell , cell cycle , cell culture , cell migration , cytotoxicity , chemistry , viability assay , flow cytometry , cell , microbiology and biotechnology , biology , in vitro , cancer , medicine , biochemistry , genetics
We investigated activity and mechanism of action of two AhR ligand antitumor agents, AFP 464 and 5F 203 on human renal cancer cells, specifically examining their effects on cell cycle progression, apoptosis, and migration. TK‐10, SN12C, Caki‐1, and ACHN human renal cancer cell lines were treated with AFP 464 and 5F 203. We evaluated cytotoxicity by MTS assays, cell cycle arrest, and apoptosis by flow cytometry and corroborated a mechanism of action involving AhR signal transduction activation. Changes in migration properties by wound healing assays were investigated: 5F 203‐sensitive cells show decreased migration after treatment, therefore, we measured c‐Met phosphorylation by Western blot in these cells. A 5F 203 induced a decrease in cell viability which was more marked than AFP 464. This cytotoxicity was reduced after treatment with the AhR inhibitor α‐NF for both compounds indicating AhR signaling activation plays a role in the mechanism of action. A 5F 203 is sequestered by TK‐10 cells and induces CYP1A1 expression; 5F 203 potently inhibited migration of TK‐10, Caki‐1, and SN12C cells, and inhibited c‐Met receptor phosphorylation in TK‐10 cells. AhR ligand antitumor agents AFP 464 and 5F 203 represent potential new candidates for the treatment of renal cancer. A 5F 203 only inhibited migration of sensitive cells and c‐Met receptor phosphorylation in TK‐10 cells. c‐Met receptor signal transduction is important in migration and metastasis. Therefore, we consider that 5F 203 offers potential for the treatment of metastatic renal carcinoma. J. Cell. Biochem. 118: 4526–4535, 2017. © 2017 Wiley Periodicals, Inc.