Baicalin-loaded folic acid-modified albumin nanoparticles (FA-BSANPs/BA) induce autophagy in MCF-7 cells via ROS-mediated p38 MAPK and Akt/mTOR pathway

Fengjie Liu,Dongmei Fan,Tiange Cai,Zhaodi Kong,Meng Lan,Baoqi Ren,Lihong Li,Tengteng Zou,Yu Cai

doi:10.1186/s12645-021-00110-x

Abstract

BackgroundBreast cancer is the most frequently occurring cancer among women. Baicalin has been shown to inhibit breast cancer proliferation, but poor aqueous solubility and unknown mechanism of action limit its application. This study aimed to investigate the antiproliferative effects of baicalin-loaded folic acid-modified albumin nanoparticles (FA-BSANPs/BA) in breast cancer MCF-7 cells and its relationship with autophagy and ROS-mediated p38 MAPK and Akt/mTOR signaling pathways. Cell viability was detected by MTT assay. Flow cytometry and fluorescence microscopy were used to detect cell cycle, apoptosis and autophagy. Western blot was used to detect protein expression.ResultsCompared with the control and free baicalin groups, FA-BSANPs/BA inhibited viability of MCF-7 cells and increased cells in S phase, apoptotic bodies, pro-apoptotic proteins, autophagy markers and autophagosomes. These effects could be reversed when combined with the autophagy inhibitor 3-methyladenine. FA-BSANPs/BA increased the levels of phosphorylated p38 MAPK, inhibited the levels of phosphorylated Akt and mTOR, and increased the level of ROS in MCF-7 cells. The effects of FA-BSANPs/BA could be reversed or enhanced using inhibitors of Akt, mTOR, p38 MAPK and ROS scavengers.ConclusionsEncapsulation in folate albumin nanoparticles improved the antiproliferative activity of baicalin. FA-BSANPs/BA induced autophagy and apoptosis via ROS-mediated p38 MAPK and Akt/mTOR signaling pathways in human breast cancer cells.

Highlights

Breast cancer (BC) remains the most prevalent cancer among women, accounting for22.9% of all cancers in women (De Cicco et al 2019; Siegel et al 2020)
The particle size, zeta-potential, encapsulation efficiency and drug loading of FABSANPs/BA are shown in Table 1, which characterize them as small particle size with narrow distribution range and good polydispersity
folic acid (FA)-BSANPs and FA-BSANPs/BA had the characteristic absorption peak of amide bond in BSA at 1654 cm−1 and the characteristic absorption peak of benzene ring in FA at 1458 cm−1, and that FA-BSANPs/BA had the characteristic absorption peak of phenolic hydroxyl group in BA at 3393 cm−1, indicating that BA was introduced into the conjugates of FA with albumin

Summary

Introduction

Breast cancer (BC) remains the most prevalent cancer among women, accounting for22.9% of all cancers in women (De Cicco et al 2019; Siegel et al 2020). Drugs have been successfully developed using folic acid (FA)modified albumin nanoparticles as carriers, such as paclitaxel (Zhao et al 2010), mitoxantrone (Zhang et al 2010), doxorubicin (Shen et al 2011), resveratrol (Lian et al 2019), and others. Baicalin has been shown to inhibit breast cancer proliferation, but poor aqueous solubility and unknown mechanism of action limit its application. This study aimed to investigate the antiproliferative effects of baicalin-loaded folic acid-modified albumin nanoparticles (FA-BSANPs/BA) in breast cancer MCF-7 cells and its relationship with autophagy and ROS-mediated p38 MAPK and Akt/mTOR signaling pathways. Flow cytometry and fluorescence microscopy were used to detect cell cycle, apoptosis and autophagy.

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