Berberine loaded nanoparticles as promising therapeutic modalities for liver and lung cancer.
Paper ID : 1044-ISCBAS
Authors
Doaa Ahmad Ghareeb *
Bio‑screening and preclinical trial lab, Biochemistry Department, Faculty of Science, Alexandria University.
Abstract
The objective of this work was the assessment of different berberine nanoparticles forms' effects on mTOR/PI3K/autophagy/apoptotic/inflammatory signaling pathway in cancer induced in experimental animal and on cancer cell lines. To achieve this objective, AMPK, Sirt1, Sigma 1, P62, mTOR, PI3K, LC3, IL1b, TNF-a and IL 6 were assessed by ELISA or by western blot. P53, BCL2, BAX, Akt, PGC-1a, VEGF, PTEN and GAPDH were analyzed by qPCR in two animal models and in vitro on CaCo-2, HEPG-2 and A549. Our obtained results in vivo and in vitro prove that cancer cells or carcinogenic rats had high level of Sirt1, P62, mTOR, Akt, PGC1 α, PI3K, angiogenesis marker (VEGF) inflammatory markers (IL1β, TNF-α and IL6), cell proliferation markers ((Sirt1 and BCL2) and low level of mTOR inhibitor (AMPK), autophagic marker (S1R, LC3 and Beclin1) and proapoptotic marker (BAX and P53) and anti-angiogenesis marker (PTEN). The treatment with Berberine albumin NPs or berberine liposome improved these abnormalities where they induced autophagy and apoptosis by inhibiting mTOR/PI3K/Akt pathway. Beside that berberine silica NPs had anti lung cancer effect in vitro by stimulating the production of P53. In conclusion, PI3K/AKT/mTOR signaling pathway is active in cancer cells that stimulated lipogenesis, cell proliferation and mitochondria stress. All treatments reversed this mechanism as all of them inhibit PI3K/AKT/mTOR signaling pathway and prevent cell proliferation and angiogenesis. Moreover, the nano-formulations increased the anticancer activity of berberine.
Keywords
Berberine/Silica, Berberine/Albumin, Berberine/liposome, autophagy
Status: Abstract Accepted (Oral Presentation)