Exploring potential additive effects of 5-fluorouracil, thymoquinone, and coenzyme Q10 triple therapy on colon cancer cells in relation to glycolysis and redox status modulation

Journal of the Egyptian National Cancer Institute, Journal Year: 2025, Volume and Issue: 37(1)

Published: March 10, 2025

Abstract Background To investigate the anticancer effects of 5-Fluorouracil (5-FU), thymoquinone (TQ), and/or coenzyme Q10 (CQ10), alone and combined, in HT29, SW480, SW620 human colorectal cancer (CRC) cell lines. Methods Cell cycle progression apoptosis were assessed by flow cytometry. Gene protein expression molecules involved (BLC2, survivin, BAX, Cytochrome-C, Caspase-3), (CCND1, CCND3, p21, p27), PI3K/AKT/mTOR/HIF1α oncogenic pathway, glycolysis (LDHA, PDH, PDHK1) also analysed quantitative RT-PCR Western blot. Oxidative stress markers (ROS/RNS, MDA, Protein carbonyl groups) antioxidants (GSH CAT) quantified ELISA. Results All treatments resulted depicted arrest apoptosis, with TQ demonstrating greater efficacy than CQ10, both without 5-FU. However, 5-FU/TQ/CQ10 triple therapy exhibited most potent pro-apoptotic activity all lines, portrayed lowest levels oncogenes BCL2, survivin) highest upregulation tumour suppressors (p21, p27, Caspase-3). The showed strongest suppression a concurrent increase its endogenous inhibitors (PTEN AMPKα) lines used. Additionally, favoured glucose oxidation upregulating while decreasing LDHA PDHK1 enzymes. displayed significant decline antioxidant increases oxidative markers. Conclusions This study is first to demonstrate superior compared 5-FU, CRC treatment. Moreover, this report reveal improved therapy, potentially through promoting phosphorylation, attenuating increasing stress-induced apoptosis. Graphical Human colon cells (HT29, & SW620) treated individually for 12h. related PI3K/AKT/mTOR glycolytic enzymes, measured. protocol revealed best

Language: Английский

Novel Perspectives in the Management of Colorectal Cancer: Mechanistic Investigations Into the Reversal of Drug Resistance via Active Constituents Derived From Herbal Medicine

Phytotherapy Research, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 26, 2024

ABSTRACT The high incidence and mortality rate of colorectal cancer have become a significant global health burden. Chemotherapy has been the traditional treatment for demonstrated promising antitumor effects, leading to improvements in patient survival. However, development chemoresistance poses major challenge during chemotherapy cancer, significantly impeding efficacy affecting prognosis. Despite variety novel anticolorectal agents, their effectiveness side effects vary, possibly due complex mechanisms resistance cancer. Abnormal drug metabolism or protein targets are most direct causes resistance. Further studies revealed that these involve biochemical processes such as altered expression, autophagy, epithelial–mesenchymal transitions. Herbal active ingredients offer an alternative option shown promise reversing This paper aims summarize role various key occurrence maintenance Additionally, it elaborates on action herbal article also discusses limitations opportunities developing drugs based medicine.

Language: Английский