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Anti-Cancer Agents in Medicinal Chemistry

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ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

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Research Article

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

Author(s): Nastaran Bani, Farzad Rahmani, Neda Shakour, Forouzan Amerizadeh, Ghazaleh Khalili-Tanha, Majid Khazaei, Seyed Mahdi Hassanian, Mohammad Amin Kerachian, Mohammad Reza Abbaszadegan, Majid Mojarad, Farzin Hadizadeh, Gordon A. Ferns and Amir Avan*

Volume 24, Issue 12, 2024

Published on: 04 April, 2024

Page: [916 - 927] Pages: 12

DOI: 10.2174/0118715206296355240325113920

Price: $65

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.

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