Improved drug delivery and anti-tumor efficacy of combinatorial liposomal formulation of genistein and plumbagin by targeting Glut1 and Akt3 proteins in mice bearing prostate tumor

• Published in: Colloids and surfaces, B, Biointerfaces Vol. 190; p. 110966
• Main Authors: Song, Yuan-yuan, Yuan, Ye, Shi, Xu, Che, Yuan-yuan
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2020
• Subjects: Animals; antineoplastic activity; antineoplastic agents; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; blood vessels; Cell Proliferation - drug effects; Cells, Cultured; Drug delivery; Drug Delivery Systems; Drug Screening Assays, Antitumor; encapsulation; Genistein; Genistein - chemistry; Genistein - pharmacology; Glucose; Glucose Transporter Type 1 - antagonists & inhibitors; Glucose Transporter Type 1 - metabolism; Humans; Liposomes - chemistry; Male; men; Mice; Nanoliposomes; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; neoplasm cells; Neoplasms, Experimental - drug therapy; Neoplasms, Experimental - metabolism; Neoplasms, Experimental - pathology; Particle Size; PC-3 Cells; Plumbagin; prostatic neoplasms; Prostatic Neoplasms - drug therapy; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Proto-Oncogene Proteins c-akt - antagonists & inhibitors; Proto-Oncogene Proteins c-akt - metabolism; signal transduction; Surface Properties; toxicity; transporters; Wound Healing - drug effects; Nanoliposomes; Drug delivery; Glucose; Plumbagin; Genistein
• ISSN: 0927-7765; 1873-4367; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.110966

[Display omitted] •Development of genistein and plumbagin encapsulated nanoliposomes for prostate cancer treatment.•Formulation lead to the inhibition of PI3K/AKT3 signaling pathway and decrease in Glut-1 transporters.•The formulation showed selective anticancer effect in prostate cancer cells and tumors.•Decrease in proliferative cells and blood vessels were found to be early biological processes leading to anti-tumor effect. Despite the plethora of significant research progress made to develop novel strategies for the treatment of prostate cancer, this disease remains one of the major global health challenges among men. However, using a co-treatment approach utilizing two or more anticancer drugs has shown tremendous success in the treatment of many cancer types. Nanoliposomes are well known to encapsulate multiple drugs and deliver them at the desired site. In this work, we report the synthesis of nanoliposomes (∼100 nm) encapsulating two drugs, plumbagin, and genistein, to synergistically inhibit the growth of prostate cancer cells. The combination of plumbagin and genistein drugs was found inhibiting xenograft prostate tumor growth by ∼80 % without any appreciable toxicity. Mechanistically, the combination of plumbagin and genistein containing nanoliposomes leads to the inhibition of PI3K/AKT3 signaling pathway as well as the decreased population of Glut-1 transporters to impart the retardation in tumor growth. Decrease in proliferative cells and blood vessels are early biological processes that laid the foundation of the observed anti-tumor effect. Thus, a novel, and non-toxic liposomal formulation, containing plumbagin and genistein drugs, is reported, which can deliver anticancer agents to prostate tumors and inhibit the growth.