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-κB signaling pathways. In conclusion, the obviously enhanced antitumor effect further demonstrated that HA/TN-DLP may be a promising tumor-targeting agent.