Cryptolepine Analog exhibits Antitumor Activity against Ehrlich Ascites Carcinoma Cells in Mice via Targeting Cell Growth, Oxidative Stress, and PTEN/Akt/mTOR Signaling Pathway

Bishoy El-Aarag; Eman S Shalaan; Abdullah A S Ahmed; Ibrahim El Tantawy El Sayed; Wafaa M Ibrahim

doi:10.2174/0118715206274318231128072821

Cryptolepine Analog exhibits Antitumor Activity against Ehrlich Ascites Carcinoma Cells in Mice via Targeting Cell Growth, Oxidative Stress, and PTEN/Akt/mTOR Signaling Pathway

Anticancer Agents Med Chem. 2024 Jan 4. doi: 10.2174/0118715206274318231128072821. Online ahead of print.

Authors

Bishoy El-Aarag^{1

2

3}, Eman S Shalaan¹, Abdullah A S Ahmed⁴, Ibrahim El Tantawy El Sayed⁴, Wafaa M Ibrahim⁵

Affiliations

¹ Center for Targeted Drug Delivery, Department of Biomedical and Pharmaceutical Sciences, Chapman University School of Pharmacy, Harry and Diane Rinker Health Science Campus, Irvine, CA, 92618, USA.
² Division of Chemistry and Biotechnology, Graduate School of Natural Science and Technology, Okayama University, Okayama, 7008530, Japan.
³ Biochemistry Division, Department of Chemistry, Faculty of Science, Menoufia University, Shebin El-Koom, 32512, Egypt.
⁴ Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Koom, Egypt.
⁵ Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt.

PMID: 38305388
DOI: 10.2174/0118715206274318231128072821

Abstract

Background: The efficacy of chemotherapy continues to be limited due to associated toxicity and chemoresistance. Thus, synthesizing and investigating novel agents for cancer treatment that could potentially eliminate such limitations is imperative.

Objective: The current study aims to explore the anticancer potency of cryptolepine (CPE) analog on Ehrlich ascites carcinoma cells (EACs) in mice.

Methods: The effect of a CPE analog on EAC cell viability and ascites volume, as well as malonaldehyde, total antioxidant capacity, and catalase, were estimated. The concentration of caspase-8 and mTOR in EACs was also measured, and the expression levels of PTEN and Akt were determined.

Results: Results revealed that CPE analog exerts a cytotoxic effect on EAC cell viability and reduces the ascites volume. Moreover, this analog induces oxidative stress in EACs by increasing the level of malonaldehyde and decreasing the level of total antioxidant capacity and catalase activity. It also induces apoptosis by elevating the concentration of caspase-8 in EACs. Furthermore, it decreases the concentration of mTOR in EACs. Moreover, it upregulates the expression of PTEN and downregulates the expression of Akt in EACs.

Conclusion: Our findings showed the anticancer activity of CPE analog against EACs in mice mediated by regulation of the PTEN/Akt/mTOR signaling pathway.

Keywords: Akt; Caspase 8.; Cryptolepine; Ehrlich carcinoma cells; PTEN; mTOR.