Anticancer property of Hemp Bioactive Peptides in Hep3B liver cancer cells through Akt/GSK3β/β‐catenin signaling pathway

Abstract

Foodborne protein hydrolysates exhibit biological activity that may be therapeutic in a number of human disease settings. Hemp peptides (HP) generated by controlled hydrolysis of hemp proteins have a number of health benefits and are of pharmaceutical value. In the present study, we produce small molecular weight HP from hemp seed and investigate its anticancer properties in Hep3B human liver cancer cells. We demonstrate that HP treatment increased apoptosis, reduced cell viability, and reduced cell migration in Hep3B human liver cancer cells without affecting the normal liver cell line L02. We correlate these phenotypes with increased cellular ROS levels, upregulation of cleaved caspase 3 and Bad, and downregulation of antiapoptotic Bcl‐2. HP treatment led to increased Akt and GSK‐3β phosphorylation, with subsequent downregulation of β‐catenin, suggesting β‐catenin signaling modulation as a critical mechanism by which HP exhibits anticancer properties. Our findings suggest HP are of potential therapeutic interest for liver cancer treatment.

Sustainable Food Systems: The Case of Functional Compounds towards the Development of Clean Label Food Products

“…These functional compounds can be obtained via enzymatic hydrolysis and microbial fermentation. There are a great number of review and research articles that have been published in the literature dealing with novel bioactive peptides isolated from different sources, such as food-based ones [ 41 , 43 ], from dairy products [ 44 ], from cereal-based foods such as amaranth, quinoa and chia [ 42 , 45 ], those of microbial origin [ 46 ], and those that are plant-based such as those from hemp [ 47 ].…”

A review on the techno‐functional, biological, and health‐promoting properties of hempseed‐derived proteins and peptides

“…Bioactive proteins derived from legumes, marine organisms and some agricultural wastes, and peptides isolated from them represent emerging anticancer entities due to their remarkable selective cytotoxicity against cancer cells while sparing normal cells (Cicero et al, 2017; Kuerban et al, 2020; Moon et al, 2017). Recently, the effects of HSPs hydrolyzed with papain‐neutral protease against liver cancer (Hep3B) and normal liver (L02) cells were investigated (Wei et al, 2021). At 10 mg/ml, the hydrolysates, composed mainly of low molecular weight peptides, demonstrated selective cytotoxic properties as characterized by reduction in over 50% viability and proliferation of Hep3B cells without affecting L02 cells.…”

“…This study further showed that the hydrolysates elevated matrix metalloproteinase (MMP) level leading to reduced metastasis. Additionally, treatment of Hep3B cells with the hydrolysates increased intracellular and mitochondrial ROS generation and caspase 3 expression leading to apoptosis via an increase in glycogen synthase kinase‐3 beta (GSK‐3β) and β‐catenin phosphorylation, and suppression of protein kinase B (Akt) phosphorylation and Bcl2 expression (Wei et al, 2021). Upregulation of GSK‐3β/β‐catenin signaling has been implicated in the progression and survival of many cancer cells (Zhang et al, 2003; Zhu et al, 2011).…”

Pharmacological properties, therapeutic potential, and legal status of Cannabis sativa L.: An overview

“…According to the findings, hemp peptides may be a potential anticancer treatment for liver cancer; however, more study on the anticancer capabilities of foodborne protein hydrolysates is needed (Wei et al, 2021).…”

“…The approach resulted in Akt and GSK‐3β phosphorylation, followed by β‐catenin downregulation, showing that β‐catenin signaling modulation is the mechanism controlling anticancer ability. According to the findings, hemp peptides may be a potential anticancer treatment for liver cancer; however, more study on the anticancer capabilities of foodborne protein hydrolysates is needed (Wei et al, 2021).…”