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

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Abstract

Aim:

This study was designed to investigate the mechanism underlying cancer cell apoptosis caused by selenophenoquinolinones and coumarins.

Materials and methods:

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.

Results:

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.

Conclusion:

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.

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