Glycyrrhizin Mediates Downregulation of Notch Pathway Resulting in Initiation of Apoptosis and Disruption in the Cell Cycle Progression in Cervical Cancer Cells

Abstract

Growing emphasis on exploring the antiproliferative potential of natural compounds has gathered momentum for the formulation of anticancer drugs. In the present study, the anticancer and apoptotic potential of glycyrrhizin (GLY) was studied on HPV^– C33A cervical cancer (CCa) cells. Our results indicated that GLY exerted antiproliferative effects in the C33A cells by inducing significant cytotoxicity. Treatment with GLY substantially increases the apoptosis in a dose-dependent manner via disrupting the mitochondrial membrane potential. GLY induced apoptosis in C33A cells via activation of capsase-9 (intrinsic pathway) and caspase-8 (extrinsic pathway) along with the modulation of pro- and antiapoptotic protein expression. Moreover, GLY also exerted cell cycle arrest in C33A cells at G₀/G₁ phase which was associated with the decreased expression of cyclin D1 and cyclin-dependent kinase 4 (CDK4) along with the increased expression of CDK inhibitor p21^Cip1. Furthermore, GLY treated CCa cells exhibited significant downregulation of Notch signaling pathway which may be associated with increased apoptosis as well as cell cycle arrest in C33A CCa cells. Thus, GLY could be an appendage in the prevention and management of CCa.

Additional information

Funding

The authors are thankful to the Deanship of Scientific Research, King Khalid University, Abha, Saudia Arabia, for financially supporting this work through the General Research Project under grant number (R.G.P. 01/48/42).