Curcumin-loaded nanostructured lipid carrier induced apoptosis in human HepG2 cells through activation of the DR5/caspase-mediated extrinsic apoptosis pathway.

Abstract

Curcumin is a lipophilic anti-cancer compound extracted from turmeric. Our previous study demonstrated that the curcumin-loaded nanostructured lipid carrier (Cur-NLC) exhibits superior anti-cancer activity in inhibiting proliferation as well as inducing apoptosis of human HepG2 cells compared to native curcumin. This study aims to unveil the mechanisms underlying the pro-apoptotic effect of Cur-NLC on HepG2 cells. Evidence indicates that low expression of death receptors (DRs) on cancer cell membranes leads to attenuated apoptosis signaling. This study showed that Cur-NLC significantly increased total expression of DR5 protein while simultaneously upregulated cell membrane expression of DR5. Cur-NLC significantly increased caspase-8 and caspase-3 activities, accompanied by increased apoptosis. Furthermore, enhanced apoptosis was inhibited in the presence of a pan-caspase inhibitor, Z-VAD-FMK. Therefore, Cur-NLC induced activation of the extrinsic apoptosis pathway via modulating the DR5/caspase-8/-3 mediated apoptosis pathway in HepG2 cells, suggesting that Cur-NLC is a promising therapeutic agent or supplement for the treatment of hepatocellular carcinoma.

• Authors: Fengling Wang, Xi Ye, Dandan Zhai, Wenting Dai, Yifan Wu, Jin Chen, Weidong Chen
• Journal: Acta pharmaceutica (Zagreb, Croatia) (Acta Pharm) Vol. 70 Issue 2 Pg. 227-237 (Jun 01 2020) ISSN: 1846-9558 [Electronic] Poland
• PMID: 31955141 (Publication Type: Journal Article)

Chemical References

• Drug Carriers
• Lipids
• Receptors, TNF-Related Apoptosis-Inducing Ligand
• TNFRSF10B protein, human
• Caspases
• Curcumin

Topics

• Apoptosis (drug effects)
• Carcinoma, Hepatocellular (diet therapy)
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Curcumin (pharmacology)
• Drug Carriers (chemistry)
• Gene Expression Regulation, Neoplastic (drug effects)
• Hep G2 Cells
• Humans
• Lipids (chemistry)
• Liver Neoplasms (drug therapy)
• Nanostructures (administration & dosage)
• Receptors, TNF-Related Apoptosis-Inducing Ligand (metabolism)
• Signal Transduction (drug effects)