Nano-liposomal zein hydrolysate for improved apoptotic activity and therapeutic index in lung cancer treatment

Abstract

Lung cancer is one of the most common cancers in the world with a high mortality rate. Zein is a protein compound whose protein isolate is not useful and whose protein hydrolysis produces biological activity. By encapsulating this bioactive compound inside the nanoparticles (NPs), it causes itself to reach the tumor site and destroy it rapidly. In this study, the effects of zein hydrolysate (ZH) and nano-liposomal ZH (N-ZH) were investigated on the human A549 cell line. Western blotting and cell cycle analyses showed that ZH and N-ZH caused cytotoxicity. They induced apoptosis via cell cycle arrest at the G0 phase, as well as significant increases in pro-apoptotic genes, such as Bax, caspase-3, -8, -9, and p53, accompanied with significant decreases in the anti-apoptotic marker Bcl-2. Based on the results, the cytotoxic and anticancer effects of N-ZH were higher than those of free ZH. In conclusion, liposomes improved the performance of ZH and dramatically reduced the IC 50 value of ZH. These findings provided the experimental evidence that N-ZH with favorable anticancer activity can be used as a therapeutic agent and strategy for lung cancer treatment in future clinical trials.

ZIP transporters‐regulated Zn2+ homeostasis: A novel determinant of human diseases

“…Lung cancer is a malignant tumor originating from the epithelium or glands of the bronchial mucosa (Bai et al, 2022). Chemotherapy, radiation therapy, targeted biological therapy, and immunotherapy are the current methods for treating lung cancer (Mazloum‐Ravasan et al, 2022). However, chemotherapy failure is a major challenge in the treatment of lung cancer.…”

In vitro/in vivo identification of zein degraded peptides using HPLC-MS/MS and their safety evaluation

“…Liang et al reported that zein hydrolysate produced by thermolysin had no cytotoxicity against Caco-2 cell lines up to 50 mg ml −1 [29]. However, a few recent reports reported that zein hydrolysate produced by alcalase enzyme has cytotoxicity and can be used for controlling growth of HepG2 or A549 cells [30,31]. The composition of peptides present in zein hydrolysate may vary depending upon enzyme used, that may cause different cytocompatibility.…”

Effect of chitosomes loaded zein on physicochemical, mechanical, microbial, and sensory characteristics of probiotic Kashk during cold storage

“…Zein, an alcohol-soluble protein comprising 45–50% of maize endosperm protein, is considered GRAS (generally recognized as safe), non-toxic, and biodegradable. It forms spherical nanoparticles widely used in pharmaceuticals, food, and biotechnology ( Liang et al, 2018 ; Mazloum-Ravasan et al, 2022 ). Despite being widely used, zein isolate (native zein) is unsuitable for direct human consumption due to its negative nitrogen balance and poor water solubility.…”

“…Despite being widely used, zein isolate (native zein) is unsuitable for direct human consumption due to its negative nitrogen balance and poor water solubility. Protein hydrolysis can be used to overcome these issues, which improves zein's functionality by chemically or biologically modifying its structure and properties ( Mazloum-Ravasan et al, 2022 ; Najafi Rashed et al, 2024 ). Zein hydrolysate offers anti-inflammatory, antioxidant, and antibacterial benefits, but stomach acid might weaken these effects ( Liang et al, 2018 ).…”

“…Notably, liposomes are attractive due to their ability to shield bioactive compounds from stomach acid and enhance intestinal absorption, ultimately improving the bioactivity and bioavailability of encapsulated zein hydrolysate ( Ramezanzade et al, 2017 ). Their unique structure allows them to encapsulate various molecules, including zein hydrolysate ( Mazloum-Ravasan et al, 2022 ). However, liposomes face limitations, such as degradation by digestive enzymes and aggregation, which can hinder release.…”