Piperlongumine mediated apoptosis in cervical cancer cells beyond docking predictions

Cervical cancer is the 4th most prevalent cancer in women. Despite its global health impact, cervical cancer research has achieved limited success with various therapies (chemo, radio, chemo-radio, surgery, etc.). Recent decades have seen no improvement in survival rates due to cancer recurrence and long-term health concerns. These treatments show the need for a new herbal approach as alternative therapy for cancer. Piperlongumine is one of numerous perfected phytochemicals with anticancerous properties. In this study, in silico simulations demonstrate various novel properties of Piperlongumine. Molecular docking was performed between receptor and ligand by simulating molecular interactions in the pro and anti-apoptotic proteins B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and Bcl-2 antagonist/killer (Bak). The docking scores of Piperlongumine with Bcl-2, Bak, and Bax are -7.02, -6.78, and -7.54 kcal/mol, respectively. Piperlongumine was also bio-tested for anticancer activities against cervical cancer cells (SiHa). Piperlongumine showed compromised cell viability, promoted apoptosis, higher nuclear condensation, reduction in mitochondrial membrane potential, increase in reactive oxygen species level, promoted cell cycle arrest, upregulation of pro-apoptotic gene whereas downregulation of anti-apoptotic genes. <i>In vitro</i> studies revealed that Piperlongumine targets apoptotic pathway in cervical cancer and could be a possible effective treatment for cervical cancer. Additional <i>in vivo</i> research is needed to explore the potential of Piperlongumine to improve treatment outcomes.