Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Siegesbeckia orientalis Suppresses Growth and Migration through Apoptosis and Inhibition of Matrix Metalloproteinases Expression on Hepatoma in Mice

Version 1 : Received: 19 February 2024 / Approved: 19 February 2024 / Online: 20 February 2024 (05:59:14 CET)

How to cite: Chen, T.; Houng, J.; Chang, T.; Chen, Y.; Chang, C.; Chang, L. Siegesbeckia orientalis Suppresses Growth and Migration through Apoptosis and Inhibition of Matrix Metalloproteinases Expression on Hepatoma in Mice. Preprints 2024, 2024021041. https://doi.org/10.20944/preprints202402.1041.v1 Chen, T.; Houng, J.; Chang, T.; Chen, Y.; Chang, C.; Chang, L. Siegesbeckia orientalis Suppresses Growth and Migration through Apoptosis and Inhibition of Matrix Metalloproteinases Expression on Hepatoma in Mice. Preprints 2024, 2024021041. https://doi.org/10.20944/preprints202402.1041.v1

Abstract

This study investigated the inhibitory effect of Siegesbeckia orientalis ethanolic extract (SOE) on growth and metastasis of hepatic tumors in C57BL/6JNarl mice, which is the model of tumor-igenesis induced by subcutaneous injection of Hepa1-6 murine hepatoma cells on the back of mice. Feeding 25 mg SOE/kg BW daily for 14 days effectively reduced the hepatoma weight in tu-mor-bearing mice by 59.7%. SOE intervention reduced the expression of anti-apoptotic Bcl-2 gene in tumor tissue by 48.5% and down-regulated the antioxidant system, by reducing the gene ex-pression of catalase (48.0%), glutathione peroxidase (46.3%), and superoxide dismutase (32.0%). In addition, SOE intervention increased the production of ROS by 21.4%, and the gene expression of pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 by 135.3%, 179.3% and 91.7%, respectively, indicating that SOE intervention promoted the acute inflammatory response. Results of H&E staining analysis showed that SOE had the ability to inhibit angiogenesis in tumor tissue. Fur-thermore, SOE treatment inhibited the expression of migration-related genes, such as MMP-2, MMP-7, MMP-9 and β-catenin, and the inhibition rates were 24.8%, 27.4%, 10.4% and 21.9%, respectively. These results imply that SOE had the ability to suppress tumor metastasis. On the other hand, SOE intervention decreased the serum contents of inflammatory cytokines, such as TNF-α, IL-1β and IL-6 by 27.4%, 30.4%, and 30.7%, respectively, indicating that SOE intervention has an anti-inflammatory effect on normal tissues of mice. Since SOE intervention had no signif-icant effect on liver and kidney weights, and no mice died throughout the experiment, it shows that it is safe to feed SOE under this experimental condition. Based on the above results, SOE has a great potential to be used in the treatment of hepatoma.

Keywords

Siegesbeckia orientalis; hepatoma-bearing mice; tumor growth; apoptosis; oxidative stress; inflammatory response

Subject

Medicine and Pharmacology, Complementary and Alternative Medicine

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