CHEMOPREVCHEMOPREV

Indonesian Journal of Cancer ChemopreventionIndonesian Journal of Cancer Chemoprevention

Hepatitis B virus (HBV) reactivation-related hepatocellular carcinoma (HCC) presents a significant threat due to its potential to cause liver failure and mortality. Consequently, the discovery of novel treatments that offer anticancer efficacy and liver protection is urgently needed. Brazilin, a natural compound, has previously been reported to possess cytotoxic and liver-protective properties. This research aimed to investigate the potency of brazilin in suppressing the growth of HCC cells through in silico and in vitro approaches. Hep3B cells, which harbor integrated HBV DNA, were selected as the HCC model, with PGV-1 utilized as a positive control. The in silico study used network pharmacology to predict brazilins potential gene targets. Cytotoxicity was evaluated using the CCK-8 assay, and apoptosis detection was carried out using Annexin V/PI staining followed by flow cytometry. The analysis predicted that brazilin targets key genes such as SRC, EGFR, AKT1, GRB2, IGF1, ESR1, STAT1, MMP9, JAK2, and PPARG involved in cancer proliferation and metastasis. Proteins such as SRC, GRB2, and MMP9 are overexpressed in TP53-mutated HCC and linked to low survival. Brazilin showed moderate cytotoxicity with an IC50 value of 17 µM at 72 h and significantly induced apoptosis in Hep3B cells. These findings suggest that brazilin is a promising apoptosis-inducing agent for HBV-related HCC.

Brazilin and PGV-1 are predicted to share two top target genes, SRC and EGFR, in Hep3B cells.Brazilin specifically targets genes involved in apoptosis regulation, including AKT1, STAT1, MMP9, and PPARG.While exhibiting moderate cytotoxicity against Hep3B cells, brazilin significantly induces apoptosis compared to PGV-1.

Penelitian lebih lanjut perlu dilakukan untuk mengidentifikasi mekanisme molekuler pasti bagaimana brazilin memodulasi jalur pensinyalan AKT1 dan menyebabkan apoptosis pada sel Hep3B. Studi in vivo diperlukan untuk memvalidasi efektivitas dan keamanan brazilin sebagai agen antikanker pada model hewan HCC dengan infeksi HBV. Selain itu, penelitian perlu mengeksplorasi potensi kombinasi brazilin dengan kemoterapi standar untuk meningkatkan efektivitas pengobatan dan mengurangi efek samping, serta mengoptimalkan formulasi dan metode pengiriman brazilin untuk meningkatkan bioavailabilitas dan stabilitasnya dalam tubuh. Investigasi lebih lanjut juga diperlukan untuk memahami peran brazilin dalam menghambat migrasi sel kanker HCC, khususnya dengan menargetkan MMP9, STAT1, dan PPARG, untuk mengembangkan strategi terapeutik yang lebih komprehensif.

  1. #hep3b cell lines#hep3b cell lines
  2. #network pharmacology#network pharmacology
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Pages14
Short Linkhttps://juris.id/p-3bc
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