Novel Anticancer Mechanism of Chamuangone through the Inhibition of Oncogenic Protein-Driven Oxidative Stress
9 affiliations
- 1Department of Pharmacology, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand.
- 2Medical Degree Program, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand.
- 3Department of Physiology, Faculty of Medicine, Srinakharinwirot University, Bangkok, Thailand.
- 4Department of Pharmacology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
- 5Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand.
- 6Department of Biochemistry, Faculty of Science, Kasetsart University, Bangkok, Thailand.
- 7Center for Advanced Studies in Nanotechnology for Chemical, Food and Agricultural Industries, Kasetsart University Institute for Advanced Studies, Kasetsart University, Bangkok, Thailand.
- 8Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand.
- 9Phytomedicine and Pharmaceutical Biotechnology Excellence Center, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla, Thailand.
Abstract
Objective:: To evaluate the anticancer mechanisms of Chamuangone against cholangiocarcinoma (CCA) cells.
Methods:: Chamuangone was tested for cytotoxicity against KKU-100 and KKU-452 cells for 24 and 48 h. Apoptosis, cell proliferation, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were assessed using Annexin V, Ki-67, JC-1 assays, and DCFH-DA fluorescence probe, respectively. Oncology proteins expression was measured.
Results:: Chamuangone inhibited CCA cell growth in a dose- and time- dependent manner, with IC50 values in KKU- 100 cells of 1.175 and 0.331 μg/mL at 24 and 48 hours, respectively; in KKU- 452 cells, the IC50 values were 1.208 and 0.428 μg/mL. Consequently, Chamuangone at 1.5 and 3.0 μg/mL effectively induced both early and late apoptosis in a statistically significant manner, which correlated with a marked reduction in cell proliferation, as evidenced by the decrease in Ki-67 positive populations to 49.04% and 17.02%, respectively. Chamuangone at concentrations of 0.75, 1.5, and 3.0 μg/mL significantly induced mitochondrial dysfunction by reducing the Red/Green fluorescence ratio across all time points (3–24 h), indicating a loss of mitochondrial membrane potential that triggers apoptosis. The induction of intracellular oxidative stress was indicated by a significant increase in the high-dose group of Chamuangone. Moreover, it also suppressed the expression of key ROS- and oxidative stress–associated oncogenic proteins, including Carbonic Anhydrase IX, Enolase2, CXCL8/IL-8, Galectin-3, EGFR/ErbB1, Progranulin, FGF basic, Dkk-1, p27/kip1, Mesothelin, Survivin, leading to redox imbalance and apoptosis in KKU-100 cells.
Conclusion:: Chamuangone inhibits CCA cell proliferation by inducing apoptosis through mechanisms involving the suppression of the Ki67, loss of mitochondrial membrane potential, intracellular ROS accumulation, and downregulation of oncogenic-related proteins involved in proliferation, survival, angiogenesis, and oxidative stress. Thus, Chamuangone has significant potential as a lead compound for the development of novel CCA therapeutics.
Related
- Reversing the Hypoxic Adaptive Response in Breast Cancer Cells through Small-Molecule Inhibition of Oncogenic MicroRNA-210
- RAS inhibition limits oncogenic signaling and tumorigenesis in neuroblastoma regardless of RAS mutational status
- Selective autophagy inhibition alleviates oxidative stress-associated neurodegeneration in an AD+CCH model
- Cysteine promotes islet α-cell glucagon secretion by limiting oxidative inhibition of voltage-gated sodium channels
- Construction of polyethylene glycol-cloaked mesoporous polydopamine nanomaterials co-loaded with anticancer drugs for photo/chemotherapy of lung cancer cells and elucidation of the cell death mechanism.
BibTeX
@article{thianthong2026novel,
title = {{Novel Anticancer Mechanism of Chamuangone through the Inhibition of Oncogenic Protein-Driven Oxidative Stress}},
author = {Woraya Thianthong and Thanyarat Srichainan and Boonya Shuntawiwat and Sahaphum Laprom and Petcharat Chiangsaen and Sarinya Kongpetch and Kiattawee Choowongkomon and Pharkphoom Panichayupakaranant and Papavee Samatiwat},
journal = {Asian Pacific Journal of Cancer Prevention : APJCP},
year = {2026},
month = jun,
doi = {10.31557/apjcp.2026.27.6.2189},
url = {https://doi.org/10.31557/apjcp.2026.27.6.2189},
note = {CC BY-NC 4.0},
}
RIS
TY - JOUR
TI - Novel Anticancer Mechanism of Chamuangone through the Inhibition of Oncogenic Protein-Driven Oxidative Stress
AU - Woraya Thianthong
AU - Thanyarat Srichainan
AU - Boonya Shuntawiwat
AU - Sahaphum Laprom
AU - Petcharat Chiangsaen
AU - Sarinya Kongpetch
AU - Kiattawee Choowongkomon
AU - Pharkphoom Panichayupakaranant
AU - Papavee Samatiwat
PY - 2026
DA - 2026/06/19
JO - Asian Pacific Journal of Cancer Prevention : APJCP
DO - 10.31557/apjcp.2026.27.6.2189
UR - https://doi.org/10.31557/apjcp.2026.27.6.2189
AB - Objective:: To evaluate the anticancer mechanisms of Chamuangone against cholangiocarcinoma (CCA) cells. Methods:: Chamuangone was tested for cytotoxicity against KKU-100 and KKU-452 cells for 24 and 48 h. Apoptosis, cell proliferation, mitochondrial membrane potential, and intracellular reactive oxygen species (ROS) levels were assessed using Annexin V, Ki-67, JC-1 assays, and DCFH-DA fluorescence probe, respectively. Oncology proteins expression was measured. Results:: Chamuangone inhibited CCA cell growth in a dose- and time- dependent manner, with IC50 values in KKU- 100 cells of 1.175 and 0.331 μg/mL at 24 and 48 hours, respectively; in KKU- 452 cells, the IC50 values were 1.208 and 0.428 μg/mL. Consequently, Chamuangone at 1.5 and 3.0 μg/mL effectively induced both early and late apoptosis in a statistically significant manner, which correlated with a marked reduction in cell proliferation, as evidenced by the decrease in Ki-67 positive populations to 49.04% and 17.02%, respectively. Chamuangone at concentrations of 0.75, 1.5, and 3.0 μg/mL significantly induced mitochondrial dysfunction by reducing the Red/Green fluorescence ratio across all time points (3–24 h), indicating a loss of mitochondrial membrane potential that triggers apoptosis. The induction of intracellular oxidative stress was indicated by a significant increase in the high-dose group of Chamuangone. Moreover, it also suppressed the expression of key ROS- and oxidative stress–associated oncogenic proteins, including Carbonic Anhydrase IX, Enolase2, CXCL8/IL-8, Galectin-3, EGFR/ErbB1, Progranulin, FGF basic, Dkk-1, p27/kip1, Mesothelin, Survivin, leading to redox imbalance and apoptosis in KKU-100 cells. Conclusion:: Chamuangone inhibits CCA cell proliferation by inducing apoptosis through mechanisms involving the suppression of the Ki67, loss of mitochondrial membrane potential, intracellular ROS accumulation, and downregulation of oncogenic-related proteins involved in proliferation, survival, angiogenesis, and oxidative stress. Thus, Chamuangone has significant potential as a lead compound for the development of novel CCA therapeutics.
SN - 1513-7368
SN - 2476-762X
ER -