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Updated: Jun 29, 2025
Pre-clinical Orthotopic Murine Model of Human Prostate Cancer
Published on: August 29, 2016
Investigating the structural basis of piperine targeting AKT1 against prostate cancer through in vitro and molecular
Prakash Nayana1, Pavan Gollapalli2, Hanumanthappa Manjunatha3
1Department of PG Studies and Research in Biotechnology, Kuvempu University, Shivamogga, Karnataka, India.
Abstract:
AkT1, significantly impacts many tumours cell functions, like transcription, apoptosis, glucose metabolism, cell proliferation, and cell migration. For tumours to develop and spread, aberrant activation of AKT1 is essential. Therefore, a major focus of molecularly targeted PCa treatment is AKT1. The present study investigates the effect of piperine compared to SDF using in-vitro studies, viz colony formation assay, comet assay and AKT1 gene expression studies using human PCa cell line PC3. A cluster of approximately at least 50 cells constitutes a colony. The clonogenic assay showed that the number and size of colonies significantly decreased when treated with compounds (SDF and piperine) in comparison to the untreated cells which effectively proliferated to form more colonies. Piperine treatment showed significant inhibition of colony formation than SDF. Effective genotoxicity was observed in piperine-treated PC3 cells with an increased Tail length of 120 µm and it was moderately observed in SDF with a Tail length of 30 µm treated on PC3 cells. The control group did not show any considerable genotoxicity with a Tail length of 6 µm. Our data, both in vitro and in silico, suggested that piperine would be a good starting point for developing novel drugs for the treatment of PCa. The downstream functions of Akt1 may be inhibited by these effects, which could impede the proliferation of PCa cells. High stability of the piperine-AKT1 complex was found by the MD simulation. Higher hydrophilic residues like Lys268 and Ser205 at the active pocket may be the cause of the binding stability. Overall, the observed results confirmed the anti-PCa effect of piperine by causing effective DNA damage and proved to be genotoxic in nature against the human PCa. These effects may impede the downstream activities of Akt1 and result in PCa cell growth regression.
Insights
Piperine effectively inhibits prostate cancer (PCa) cell growth by causing DNA damage and inhibiting AKT1, showing potential as a novel PCa therapeutic agent. SDF also demonstrated inhibitory effects, but piperine was more potent.
Area of Science:
- Molecular Biology
- Cancer Research
- Pharmacology
Background:
- Aberrant activation of AKT1 is crucial for tumor development and spread, making it a key target in prostate cancer (PCa) treatment.
- AKT1 influences critical cancer cell functions including proliferation, migration, and metabolism.
Purpose of the Study:
- To investigate the in vitro and in silico effects of piperine and SDF on human PCa cell line PC3, focusing on AKT1 gene expression and genotoxicity.
- To evaluate piperine's potential as a starting point for novel PCa drug development.
Main Methods:
- In vitro studies included clonogenic, comet assay, and AKT1 gene expression analysis on PC3 cells.
- In silico methods involved molecular dynamics (MD) simulation to assess the stability of the piperine-AKT1 complex.
- Genotoxicity was assessed by measuring tail length in comet assays.
Main Results:
- Both piperine and SDF significantly reduced colony formation and size in PC3 cells compared to controls, with piperine showing greater inhibition.
- Piperine induced significant genotoxicity (120 µm tail length), while SDF showed moderate genotoxicity (30 µm tail length).
- MD simulations revealed high stability of the piperine-AKT1 complex, attributed to interactions with hydrophilic residues.
Conclusions:
- Piperine demonstrates significant anti-PCa effects by inducing DNA damage and genotoxicity, potentially by inhibiting AKT1 downstream functions.
- Piperine's potent effects and stable interaction with AKT1 suggest its promise as a novel therapeutic agent for prostate cancer.
- The study confirms piperine's anti-PCa activity and its potential for developing new drugs targeting AKT1.
