Antitumor Activity of Taxol Engross Taxol-Caveolin-1 Interaction via Lipid Raft Structure-"Caveolae"

Appl Biochem Biotechnol. 2023 Jan 24. doi: 10.1007/s12010-023-04355-7. Online ahead of print.

Abstract

Taxol is one of the most widely used natural antitumor drugs that have shown considerable success in treating cancers of different lineage. However, the development of resistance to taxol is still a significant issue. Caveolae, the cave-like structures found on the surface of many cancerous cells, are enriched in cholesterol and are known to play a pivotal role in drug uptake. Caveolin-1 (Cav-1), the principal structural proteins of the caveolae, interacts with signaling molecules through a scaffolding domain. In the present study, we observed that Cav-1-GFP clusters were instantly recruited to the cell membrane. Interestingly, Caveolae formation followed by internalization was observed after the treatment with time. The recruitment and the formation of the Cav-1-GFP clusters are provided in supplementary video 2 (SV2). The results obtained from molecular docking indicate favorable taxol-Cav-1 interaction. To further confirm the influence of Cav-1 proteins in the uptake and effects of taxol, the cells were treated with beta-cyclodextrin (β-CD), cholesterol, and taxol combinations. The result suggests that the depletion of cholesterol in HeLa cells makes them less susceptible to taxol at a lower concentration. These observations provide evidence of the interaction between Cav-1 and taxol. Further studies that may elucidate the molecular mechanism of uptake of taxol through caveolae/Cav-1 will help to determine if Cav-1 can be used to increase the uptake of taxol by cancer cells and sensitize the drug-resistant cancer cells to taxol.

Keywords: Beta cyclodextrin; Caveolae; Caveolin-1; TIRFM; Taxol.