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  • Selenopheno quinolinones and coumarins promote cancer cell apoptosis by ROS depletion and caspase-7 activation.

Selenopheno quinolinones and coumarins promote cancer cell apoptosis by ROS depletion and caspase-7 activation.

Life sciences (2017-08-16)
Ilona Domracheva, Iveta Kanepe-Lapsa, Ludmila Jackevica, Jelena Vasiljeva, Pavel Arsenyan
ABSTRACT

This study was designed to investigate the mechanism underlying cancer cell apoptosis caused by selenophenoquinolinones and coumarins. Twelve derivatives were studied according to their ability to suppress the proliferation of cancer cells in vitro (i.e., HepG2, MH-22A, MCF-7), induce cell apoptosis, modulate cellular antioxidant enzyme system activities (i.e., SOD, GPx, TrxR), influence the level of ROS, and modulate caspase activity. A plausible mechanism of apoptosis is presented. The lack of change in the activity of caspase-8 demonstrates that these compounds affect the intrinsic rather than the extrinsic pathway; moreover, the absence of caspase-9 activation suggests that the studied compounds are involved in the intrinsic pathway of apoptosis in a non-canonical manner. Provisionally, the increase in Smac/Diablo released from the mitochondria removes the inhibitory effect and activates caspase-7, leading to apoptosis. Additionally, the activation of caspase-1 activates effector caspase-7, thereby increasing the amount of cytochrome c and Smac/Diablo released from the mitochondria and ultimately leading to apoptosis. This present study provides scientific evidence that selenopheno quinolinones and coumarins promote cancer cell apoptosis by ROS depletion and caspase-7 activation in malignant cells.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Acridine Orange hydrochloride solution, ≥95.0% (HPLC), 10 mg/mL in H2O
Sigma-Aldrich
N-Acetyl-Tyr-Val-Ala-Asp-7-amido-4-trifluoromethylcoumarin, ≥95% (HPLC), powder
Sigma-Aldrich
2′,7′-Dichlorodihydrofluorescein diacetate, ≥97%
Sigma-Aldrich
N-Acetyl-Leu-Glu-His-Asp-7-amido-4-trifluoromethylcoumarin, ≥95% (HPLC), powder
Sigma-Aldrich
N-Acetyl-Asp-Glu-Val-Asp-7-amido-4-trifluoromethylcoumarin, ≥90% (HPLC), powder