Annona senegalensis extract demonstrates anticancer properties in N-diethylnitrosamine-induced hepatocellular carcinoma in male Wistar rats

Omolara F Yakubu; Damilohun S Metibemu; Isaacson B Adelani; Gbolahan O Adesina; Chidera B Edokwe; Oyinkansola E Oseha; Abiodun H Adebayo

doi:10.1016/j.biopha.2020.110786

Annona senegalensis extract demonstrates anticancer properties in N-diethylnitrosamine-induced hepatocellular carcinoma in male Wistar rats

Biomed Pharmacother. 2020 Nov:131:110786. doi: 10.1016/j.biopha.2020.110786. Epub 2020 Sep 30.

Authors

Omolara F Yakubu¹, Damilohun S Metibemu², Isaacson B Adelani³, Gbolahan O Adesina³, Chidera B Edokwe³, Oyinkansola E Oseha³, Abiodun H Adebayo⁴

Affiliations

¹ Department of Biochemistry, College of Science and Technology, Covenant University, Canaan Land, Ota PMB 1023, Ogun State, Nigeria. Electronic address: omolara.yakubu@covenantuniversity.edu.ng.
² Department of Biochemistry, Adekunle Ajasin University, Akungba-Akoko, Ondo State, Nigeria.
³ Department of Biochemistry, College of Science and Technology, Covenant University, Canaan Land, Ota PMB 1023, Ogun State, Nigeria.
⁴ Department of Biochemistry, College of Science and Technology, Covenant University, Canaan Land, Ota PMB 1023, Ogun State, Nigeria. Electronic address: abiodun.adebayo@covenantuniversity.edu.ng.

PMID: 33152944
DOI: 10.1016/j.biopha.2020.110786

Abstract

Background: Hepatocellular carcinoma (HCC) is a common and leading cancer around the globe. This study investigated the anticancer properties of extract of Annona senegalensis in N-diethylnitrosamine (DEN) - induced hepatocellular carcinoma in male Wistar rats.

Methods: Rats were simultaneously induced with a combination of 100 mg/kg b.wt of DEN and 0.5 mL/kg of carbon tetrachloride (CCl₄) intraperitoneally once a week for three weeks in a row. Thereafter, animals were treated with 100 mg/kg and 200 mg/kg b.wt of A. senegalensis extract daily for 21days. Analysis using gas chromatography-mass spectrometry (GC-MS) was carried out to discover the phytoconstituents contained in the n-hexane extract of A. senegelensis. The levels of liver function parameters and antioxidant enzyme activities were determined via spectrophotometric analysis. Reverse transcriptase-polymerase chain reaction technique was used to assess the gene expression patterns of BCL-2, P53, P21, IL-6, FNTA, VEGF, HIF, AFP, XIAP, and EGFR mRNAs.

Results: Treatment of DEN-induced hepatocellular carcinoma Wistar rats with the extract caused significant (p < 0.05) decrease in the activities of ALT and AST. It also resulted in a reduction of the concentration of MDA and a significant increase (p < 0.05) in SOD and GSH activities. IL-6, BCL-2, VEGF, EGFR, XIAP, FNTA, and P21 mRNAs expressions were significantly (p < 0.05) downregulated after treatment. Histopathological analysis revealed that the extract improved the liver architecture.

Conclusion: A. senegelensis n-hexane extract demonstrates its anticancer properties by improving the liver architecture, increasing the antioxidant defense systems, downregulating the pro-inflammatory, anti-apoptotic, angiogenic, alpha-fetoprotein and farnesyl transferase mRNAs expression and hitherto up-regulate the expression of tumor suppressor (P21 and P53) mRNAs.

Keywords: Annona senegalensis; Gene expression; Hepatocellular carcinoma; N-Diethylnitrosamine.

MeSH terms

Animals
Annona / chemistry*
Antineoplastic Agents, Phytogenic / administration & dosage
Antineoplastic Agents, Phytogenic / pharmacology*
Antioxidants / metabolism
Carbon Tetrachloride
Carcinoma, Hepatocellular / drug therapy*
Carcinoma, Hepatocellular / pathology
Diethylnitrosamine
Dose-Response Relationship, Drug
Gene Expression Regulation, Neoplastic
Liver Neoplasms, Experimental / drug therapy*
Liver Neoplasms, Experimental / pathology
Male
Plant Extracts / administration & dosage
Plant Extracts / pharmacology*
Rats
Rats, Wistar

Substances

Antineoplastic Agents, Phytogenic
Antioxidants
Plant Extracts
Diethylnitrosamine
Carbon Tetrachloride