Mechanistic exploration of the activities of poly(lactic-co-glycolic acid)-loaded nanoparticles of betulinic acid against hepatocellular carcinoma at cellular and molecular levels

• Published in: Archives of physiology and biochemistry Vol. 128; no. 3; pp. 836 - 848
• Main Authors: Kumar, Pranesh, Gautam, Anurag Kumar, Kumar, Umesh, Bhadauria, Archana S., Singh, Ashok K., Kumar, Dinesh, Mahata, Tarun, Maity, Biswanath, Bera, Hriday, Saha, Sudipta
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.05.2022
• Subjects: Bcl-2; Bcl-xl and BAX proteins; betulinic acid; H-NMR-based metabolomics; hepatocellular carcinoma; PLGA nanoparticles; Bcl-2; 1H-NMR-based metabolomics; Bcl-xl and BAX proteins; betulinic acid; PLGA nanoparticles; hepatocellular carcinoma
• ISSN: 1381-3455; 1744-4160
• DOI: 10.1080/13813455.2020.1733024

The effectiveness of betulinic acid (B) and PLGA loaded nanoparticles of B (Bnp) against hepatocellular carcinoma (HCC) was established and reported earlier. In continuation of our previous report, the present study described the molecular mechanisms of their antineoplastic responses. In this context, the antineoplastic properties of both B and Bnp were evaluated on DEN-induced HCC rat model. The quantitative real-time polymerase chain reaction and western blot analyses revealed that HCC was developed through lower expressions of e-NOS, BAX, BAD, Cyt C and higher expressions of i-NOS, Bcl-xl, Bcl-2. B and Bnp normalised the expressions of these apoptogenic markers. Particularly, both activated i-NOS and e-NOS mediated Bcl-2 family proteins→CytC→Caspase 3 and 9 signalling cascades. The 1 H-NMR-based metabolomics study also demonstrated that the perturbed metabolites in DEN-induced rat serum restored to the normal level following both treatments. Moreover, the antineoplastic potential of Bnp was found to be comparable with the marketed product, 5-flurouracil.