Wortmannin Inhibits Cell Growth and Induces Apoptosis in Colorectal Cancer Cells by Suppressing the PI3K/AKT Pathway


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Abstract

Background:Colorectal cancer (CRC) remains a significant contributor to mortality, often exacerbated by metastasis and chemoresistance. Novel therapeutic strategies are imperative to enhance current treatments. The dysregulation of the PI3K/Akt signaling pathway is implicated in CRC progression. This study investigates the therapeutic potential of Wortmannin, combined with 5‐fluorouracil (5-FU), to target the PI3K/Akt pathway in CRC.

Methods:Anti-migratory and antiproliferative effects were assessed through wound healing and MTT assays. Apoptosis and cell cycle alterations were evaluated using Annexin V/Propidium Iodide Apoptosis Assay. Wortmannin's impact on the oxidant/antioxidant equilibrium was examined via ROS, SOD, CAT, MDA, and T-SH levels. Downstream target genes of the PI3K/AKT pathway were analyzed at mRNA and protein levels using RTPCR and western blot, respectively.

Results:Wortmannin demonstrated a significant inhibitory effect on cell proliferation, modulating survivin, cyclinD1, PI3K, and p-Akt. The PI3K inhibitor attenuated migratory activity, inducing E-cadherin expression. Combined Wortmannin with 5-FU induced apoptosis, increasing cells in sub-G1 via elevated ROS levels.

Conclusion:This study underscores Wortmannin's potential in inhibiting CRC cell growth and migration through PI3K/Akt pathway modulation. It also highlights its candidacy for further investigation as a promising therapeutic option in colorectal cancer treatment.

About the authors

Nastaran Bani

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Farzad Rahmani

Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Neda Shakour

Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Forouzan Amerizadeh

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Ghazaleh Khalili-Tanha

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Majid Khazaei

Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Seyed Mahdi Hassanian

Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Mohammad Amin Kerachian

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Mohammad Reza Abbaszadegan

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Majid Mojarad

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Farzin Hadizadeh

Department of Medicinal Chemistry, School of Pharmacy, Mashhad University of Medical Sciences

Email: info@benthamscience.net

Gordon Ferns

Department of Medical Education, Brighton & Sussex Medical School

Email: info@benthamscience.net

Amir Avan

Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences

Author for correspondence.
Email: info@benthamscience.net

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