Abstract 4594: Reversal of Warburg effect by Apigenin and 5-Fluorouracil loaded dual drug liposomes result in enhanced colorectal chemotherapy

摘要: Proceedings: AACR Annual Meeting 2014; April 5-9, San Diego, CA Recent combinatorial approaches have demonstrated multidrug-based chemotherapy which target multiple pathways simultaneously leading to enhanced efficacy and reduced toxicity. Our study reports simultaneous delivery of 5-Fluorouracil (a clinically approved drug) Apigenin naturally occurring isoflavonoid abundantly present in fruit vegetables) through a single liposome combat control colon cancer effectively in-vitro in-vivo based on synergy studies after screening natural product library. Uniform homogeneous suspension dual drug-loaded large unilamellar vesicles with substantial entrapment both drugs was obtained by modified thin film hydration method. The exhibited excellent hemocompatibility cytocompatibility against normal fibroblasts. cytotoxicity cellular effects individual free drugs, neat or liposomes tested different human cell lines revealed significantly higher dual-drug comparison other formulations. drug loaded liposomal formulation observed be internalized endocytosis inhibition angiogenesis, better reduction proliferation, increased apoptotic potential decreased migration invasion capacity. Cell signaling indicating significant upregulation AMPK activity downstream targets resulted apoptosis, autophagy senescence, suggesting its role the reversal Warburg effect. Enhanced traced ability induce greater oxidative stress generation reactive oxygen nitrogen species. preclinical setting nude mice tumor xenograft model found anti-neoplastic anti-tumorigenic indicated synergistic effect treatment circumvents problem resistance associated This thus, offers new attractive alternative enhance therapeutic potency paves way for clinical applications. Note: abstract not presented at meeting. Citation Format: Kacoli Sen, Shubhadeep Banerjee, Mahitosh Mandal. Reversal result colorectal chemotherapy. [abstract]. In: Proceedings 105th American Association Cancer Research; 2014 Apr 5-9; CA. Philadelphia (PA): AACR; Res 2014;74(19 Suppl):Abstract nr 4594. doi:10.1158/1538-7445.AM2014-4594