Peptide of Trichinella spiralis Infective Larval Extract That Harnesses Growth of Human Hepatoma Cells

Abstract

Trichinella spiralis, a tissue-dwelling helminth, causes human trichinellosis through ingestion of undercooked meat containing the parasite’s infective larvae. However, benefits from T. spiralis infection have been documented: reduction of allergic diseases, inhibition of collagen-induced arthritis, delay of type 1 diabetes progression, and suppression of cancer cell proliferation. Since conventional cancer treatments have limited and unreliable efficacies with adverse side effects, novel adjunctive therapeutic agents and strategies are needed to enhance the overall treatment outcomes. This study aimed to validate the antitumor activity of T. spiralis infective larval extract (LE) and extricate the parasite-derived antitumor peptide. Extracts of T. spiralis infective larvae harvested from striated muscles of infected mice were prepared and tested for antitumor activity against three types of carcinoma cells: hepatocellular carcinoma HepG2, ovarian cancer SK-OV-3, and lung adenocarcinoma A549. The results showed that LE exerted the greatest antitumor effect on HepG2 cells. Proteomic analysis of the LE revealed 270 proteins. They were classified as cellular components, proteins involved in metabolic processes, and proteins with diverse biological functions. STRING analysis showed that most LE proteins were interconnected and played pivotal roles in various metabolic processes. In silico analysis of anticancer peptides identified three candidates. Antitumor peptide 2 matched the hypothetical protein T01_4238 of T. spiralis and showed a dose-dependent anti-HepG2 effect, not by causing apoptosis or necrosis but by inducing ROS accumulation, leading to inhibition of cell proliferation. The data indicate the potential application of LE-derived antitumor peptide as a complementary agent for human hepatoma treatment.

Trichinella spiralis Larval Extract as a Biological Anti‐Tumor Therapy in a Murine Model of Ehrlich Solid Carcinoma

“…Moreover, Ruenchit et al. [68] demonstrated that the extract of T. spiralis‐ infective larvae inhibited the proliferation of human hepatoma, ovarian cancer and lung adenocarcinoma cells. Both larvae and their derived anti‐tumor peptides (identified by proteomics and bioinformatics) showed dose‐dependent detrimental effects against hepatoma cell line (HepG2) [68].…”

“…Wang et al [64] and Elhasawy et al [4] found that T. spiralis and its extract had anti-proliferative effect in vitro in the hepatoma cell line (H7402) and in vivo in rats. Moreover, Ruenchit et al [68] demonstrated that the extract of T. spiralis-infective larvae inhibited the proliferation of human hepatoma, ovarian cancer and lung adenocarcinoma cells. Both larvae and their derived anti-tumor peptides (identified by proteomics and bioinformatics) showed dose-dependent detrimental effects against hepatoma cell line (HepG2) [68].…”

Metabolite profiling of Trichinella spiralis adult worms and muscle larvae identifies their excretory and secretory products

“…To obtain adult worms, three mice were euthanized by carbon dioxide gas after being infected for seven days. By flushing the digestive tracts with normal saline, adult worms were collected and kept at -80°C ( Ruenchit et al., 2022 ). For larvae preparation, the six infected mice were euthanized by carbon dioxide gas after 2 months of infection.…”

Omics: Applications related to diagnosis, treatment, prevention and control of parasitic diseases. Part II. Helminths

“…In silico analysis of anticancer peptides identified three candidates. Antitumor peptide 2 matched the hypothetical protein T01_4238 of T. spiralis and showed a diverse dosedependent effect on the human liver cancer HepG2 cell line, not by causing apoptosis or necrosis but by inducing ROS accumulation, leading to inhibition of cell proliferation [74] .…”