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

Abstract

Background Breast 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. Results Compared 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. Conclusions Encapsulation 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.

Study the Anticancer Properties of Thymol‐Loaded PEGylated Bovine Serum Albumin Nanoparticles Conjugated with Folic Acid

“…The effect of such signaling molecules is to increase the permeability of the mitochondrial membrane, thus making it easier for cytochrome c to be released from the mitochondria. In response to the apoptotic signal, caspase genes are activated, resulting in the cleavage of apoptosis‐related proteins (e. g. PARP), which is regulated by the Bcl proteins [38] . This study demonstrated that the synthesized nanoparticles inhibited the expression of Bcl‐2, increased the expression of BAX in a dose‐dependent manner, and that apoptosis can be induced by the change in expression of these genes.…”

“…In response to the apoptotic signal, caspase genes are activated, resulting in the cleavage of apoptosis-related proteins (e. g. PARP), which is regulated by the Bcl proteins. [38] This study demonstrated that the synthesized nanoparticles inhibited the expression of Bcl-2, increased the expression of BAX in a dose-dependent manner, and that apoptosis can be induced by the change in expression of these genes. Activating all phases of the cancer immunity process, pro-inflammatory cytokines (for instance, TNF-α) can contribute to cancer therapy.…”

Study of the anti-cancer activity of a mesoporous silica nanoparticle surface coated with polydopamine loaded with umbelliprenin

“…By stopping the cell cycle, the P53 protein prevents cancer cells from proliferating 53 . After apoptosis signals are received, caspase 3, -6, -7, -8, and -9 are activated, cleaving apoptosis-related proteins 54 . Apoptosis and the production of cytokines are both regulated by caspase-8, a cysteine protease.…”

Targeting the Interplay of Autophagy and ROS for Cancer Therapy: An Updated Overview on Phytochemicals

“…In another study, baicalin was loaded with folic acid-modified albumin nanoparticles (FA-BSANPs/BA) to improve its biocompatibility and prolong its circulation time in vivo. The FA-BSANPs/BA nanoparticles were found to elevate ROS levels, inactivate AKT/mTOR signaling, and induce cytotoxic autophagy and apoptosis in breast cancer [ 137 ]. These results demonstrate that baicalin can regulate ROS-mediated autophagy in cancer.…”