Bee venom and its active component Melittin synergistically potentiate the anticancer effect of Sorafenib against...

Area of Science:

• Oncology
• Pharmacology
• Biochemistry

Background:

• Advanced hepatocellular carcinoma (HCC) treatment faces challenges with Sorafenib (Sorf) due to severe side effects and drug resistance.
• Bee Venom (BV) and its component Melittin (Mel) possess therapeutic properties suggesting potential as anti-cancer agents or chemotherapy adjuvants.

Purpose of the Study:

• To evaluate the combined effects of BV and Mel with Sorf on HepG2 cells.
• To investigate the molecular mechanisms underlying the synergistic action of these compounds.
• To assess the potential of BV and Mel as adjuvants in HCC chemotherapy.

Main Methods:

• Computational docking of Melittin (Mel) with tumor markers.
• Cytotoxicity assays of BV, Mel, and Sorf on HepG2 and THLE-2 cells.
• Combination synergy studies (BV/Sorf, Mel/Sorf) and analysis of gene expression, oxidative stress, and cell cycle progression.

Main Results:

• Melittin (Mel) demonstrated potential binding and inhibition of key cancer-related proteins (XIAP, Bcl2, MDM2, CDK2, MMP12).
• Combinations of BV/Sorf and Mel/Sorf exhibited synergistic anti-cancer effects (Combination Index < 1) on HepG2 cells.
• Significant modulation of cancer-related gene expression (upregulation of p53, Bax, Cas3, Cas7, PTEN; downregulation of Bcl-2, Cyclin-D1, Rac1, Nf-κB, HIF-1a, VEGF, MMP9) and G2/M cell cycle arrest were observed.

Conclusions:

• Bee Venom (BV) and Melittin (Mel) demonstrate a synergistic anti-cancer effect when combined with Sorafenib (Sorf) against HepG2 cells.
• This synergistic action, involving modulation of key cancer pathways and cell cycle arrest, suggests a promising strategy for enhancing HCC treatment.
• The findings support the potential of BV and Mel as novel adjuvants in combination chemotherapy for advanced hepatocellular carcinoma.