Lophocereus schotti Polar Fraction Reduces TGFB1 Expression in Chemically Induced Hepatocarcinogenesis

Introduction and Objectives

The anticancer effect of Lophocereus schottii polar fraction (LsPF) has been tested in models of lymphoma; however, its action in hepatocellular carcinoma remains to be elucidated. The present study aims to analyse the effect of LsPF on the progress of damage induced by diethylnitrosamine (DEN) and N-2-Fluorenylacetamide (2-AAF) chronic administration.

Materials and Patients

Male Wistar rats (180-200 g) were grouped as follows: a) Control (Ctl; n=5); no treatment (Tx), b) LsPF (n=4), treated with LsPF (50 mg/Kg i.g.) 3 times a week; c) Damage (Dmg; n=6), treated with DEN (50 mg/Kg, i.p) the first day, and with 2-AAF (25 mg/Kg, i.g.) on the third day; d) Damage+LsPF (Dmg+LsPF; n=5) received the Dmg group Tx; then, Tx with LsPF started to be administrated along with the Dmg Tx at the seventh week. The Txs were sustained for 13 weeks; livers and serum were collected afterward. Hematoxylin & Eosin and Masson's Trichrome stains, and serum biochemistry were performed. Statistical parametric Student's t-tests or nonparametric Kruskal-Wallis and Mann-Whitney U were performed using the software GraphPad Prism, version 8. A p value < 0.05 was considered significant.

Results

In contrast to Ctl and LsPf groups, the weights of the groups administrated with Dmg Tx were decreased. Additionally, the Dmg Tx produced discoloration and tumors in the liver of the treated rats, and a significant increase in the ratio between the liver and animal weight. Furthermore, serum ALT, AST, ALKP, GGT, total bilirubin, and total proteins levels were increased; significant differences between the Dmg and the Dmg+LsPF groups were not found. The gene expression analysis demonstrated that expression of CAT, SOD, COL1A, and TGFB1 was significantly increased in the Dmg groups compared to the Ctl group; when these results were compared to the Ctl and the Dmg+LsPF, significant differences were not found. Moreover, TGFB1 expression levels were lower in the Dmg+LsPF compared to Dmg group. LsFP tx increased the ALT and total protein levels in serum, and the expression of CAT and COL1A by itself. Nevertheless, the histological analysis did not display any alterations due to the administration of this fraction.

Conclusions

LsPF administration did not show a significant effect over the damage on the liver; however, the gene expression analysis provided indications that this fraction might be acting over genes related to HCC development.

Ethical statement: The study protocol (code CI-01720) was approved by the Ethics, Research, and Biosecurity Committee of the Universidad de Guadalajara on 20 October 2020.

Declaration of interests: The authors declare no conflict of interest.

Funding: Grant PIN 2021 CUCS, UdeG, P3E 271879-2023 and PRO SNI UdeG.