Phyllanthus niruri potentiates apoptosis in Huh-7 cells and mitigates diethylnitrosamine-induced hepatocarcinogenesis
Annapoorna Bangalore Ramachandra1,2, Madan Kumar Perumal3,4
1Department of Biochemistry, CSIR-Central Food Technological Research Institute, Mysore, 570 020, Karnataka, India.
Abstract:
Hepatocellular carcinoma is one of the deadliest cancers occurring worldwide. Substantial evidence suggests that the Hippo-YAP pathway as a promising therapeutic target. Phyllanthus niruri is known for pharmacological activities, including hepatoprotective, anti-viral, and anti-inflammatory effects. However, there is a lacuna of molecular studies on how the bioactives in Phyllanthus niruri interacts with hippo signaling to enhance its potential for liver cancer management. This study aimed to delineate the effects of Phyllanthus niruri extract on cell proliferation and apoptosis, and its mechanisms in modulating the Hippo-YAP signaling, using Huh-7 cells and a diethylnitrosamine-induced liver cancer model in Wistar rats. MTT assay results confirmed that Phyllanthus niruri reduced the viability of Huh-7 cells in a dose-dependent manner. Notably, Phyllanthus niruri extracts decreased nuclear YAP-localization by modulating upstream regulators of the Hippo-YAP pathway and promoted apoptosis, as evidenced by increased ROS levels and the upregulation of Bax and downregulation Bcl-2 protein expression. In diethylnitrosamine-induced liver cancer rats, oral administration of Phyllanthus niruri extract significantly reduced tumor burden, activated hippo signaling, and exhibited therapeutic effects. Overall, Phyllanthus niruri extracts exhibited anti-proliferative, and pro-apoptotic effects in experimental liver cancer models offering valuable insights into their mechanism of action through modulation of the Hippo-YAP signaling pathway.
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