Targeting the PI3K/pAKT/mTOR/NF-κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk

Mohamed S Abdel-Bakky; Hamdoon A Mohammed; Nesreen I Mahmoud; Elham Amin; Mansour Alsharidah; Osamah Al Rugaie; Mohamed G Ewees

doi:10.1002/tox.24217

Targeting the PI3K/pAKT/mTOR/NF-κB/FOXO3a signaling pathway for suppressing the development of hepatocellular carcinoma in rats: Role of the natural remedic Suaeda vermiculata forssk

Environ Toxicol. 2024 Mar 20. doi: 10.1002/tox.24217. Online ahead of print.

Authors

Mohamed S Abdel-Bakky^{1

2}, Hamdoon A Mohammed^{3

4}, Nesreen I Mahmoud⁵, Elham Amin^{3

6}, Mansour Alsharidah⁷, Osamah Al Rugaie⁸, Mohamed G Ewees⁵

Affiliations

¹ Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Saudi Arabia.
² Department of Pharmacology and Toxicology, Faculty of Pharmacy, Al-Azhar University, Egypt.
³ Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, Qassim University, Saudi Arabia.
⁴ Department of Pharmacognosy and Medicinal Plants, Faculty of Pharmacy (Boys), Al-Azhar University, Egypt.
⁵ Department of Pharmacology and Toxicology, Faculty of Pharmacy, Nahda University, Egypt.
⁶ Department of Pharmacognosy, Faculty of Pharmacy, Beni-Suef University, Egypt.
⁷ Department of Physiology, College of Medicine, Qassim University, Saudi Arabia.
⁸ Department of Basic Medical Sciences, College of Medicine and Medical Sciences, Qassim University, Unaizah, Qassim, Saudi Arabia.

PMID: 38506534
DOI: 10.1002/tox.24217

Abstract

Liver malignancy is well recognized as a prominent health concern, with numerous treatment options available. Natural products are considered a renewable source, providing inspiring chemical moieties that could be used for cancer treatment. Suaeda vermiculata Forssk has traditionally been employed for management of hepatic conditions, including liver inflammation, and liver cirrhosis, as well as to improve general liver function. The findings of our earlier study demonstrated encouraging in vivo hepatoprotective benefits against liver injury generated by paracetamol and carbon tetrachloride. Additionally, Suaeda vermiculata Forssk exhibited cytotoxic activities in vitro against Hep-G2 cell lines and cell lines resistant to doxorubicin. The present investigation aimed to examine the potential in vivo hepatoprotective efficacy of Suaeda vermiculata Forssk extract (SVE) against hepatocellular carcinoma induced by diethylnitrosamine (DENA) in rats. The potential involvement of the PI3K/AKT/mTOR/NF-κB pathway was addressed. Sixty adult male albino rats were allocated into five groups randomly (n = 10). First group received a buffer, whereas second group received SVE only, third group received DENA only, and fourth and fifth groups received high and low doses of SVE, respectively, in the presence of DENA. Liver toxicity and tumor markers (HGFR, p-AKT, PI3K, mTOR, NF-κB, FOXO3a), apoptosis markers, and histopathological changes were analyzed. The current results demonstrated that SVE inhibited PI3K/AKT/mTOR/NF-κB pathway as well as increased expression of apoptotic parameters and FOXO3a levels, which were deteriorated by DENA treatment. Furthermore, SVE improved liver toxicity markers and histopathological changes induced by DENA administration. This study provided evidence for the conventional hepatoprotective properties attributed to SV and investigated the underlying mechanism by which its extract, SVE, could potentially serve as a novel option for hepatocellular carcinoma (HCC) treatment derived from a natural source.

Keywords: FOXO3a; NF-κB; Suaeda vermiculata; apoptosis; hepatocellular carcinoma; p-AKT.

Grants and funding

QU-IF-1-2-2/Deputyship for Research & Innovation, Ministry of Education in Saudi Arabia