Averrhoa carambola extractive inhibits breast cancer via regulating CEPT1 and LYPLA1

Liposomes have been widely exploited as a drug delivery system in treating tumors because of their advantage to enhance anti-tumor efficacy and reduce side effects. In this study, the tumor-targeted 2-dodecyl-6-methoxycyclohexa-2,5-diene-1,4-dione (DMDD, i.e., Averrhoa carambola extractive) liposomes (HA/TN-DLP) were conducted and assessed. HA/TN-DLP showed controllable drug loading (up to 83%) with high stability. In vitro and in vivo studies showed good cell uptake behavior and high inhibition rate of breast cancer compared to free DMDD. HA/TN-DLP might be the suitable for DMDD due to its better advantages in delivery, penetrability, and targeting-tumor capability. For in vivo mouse model tests, HA/TN-DLP effectively inhibited tumor growth compared to free DMDD. Further analyses indicated that HA/TN-DLP inhibited the glycerophospholipid metabolism pathway by reducing the biosynthesis of phosphatidylcholine and 1-acyl-sn-glycero-3-phosphocholine through regulating the expressions of CEPT1 and LYPLA1, and inhibited tumor cell growth by regulating the PI3K/Akt and NF-kappa B signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

Liposomes are widely used for drug delivery in tumor treatment due to their ability to enhance anti-tumor efficacy and reduce side effects. This study evaluated the tumor-targeted liposomes HA/TN-DLP for delivering the drug DMDD. HA/TN-DLP showed high stability and controllable drug loading, and exhibited superior cell uptake behavior and inhibition of breast cancer compared to free DMDD. The significantly enhanced anti-tumor effect demonstrated the potential of HA/TN-DLP as a promising tumor-targeting agent.