Publication: Andrographolide Induces Mitochondrial Dysfunction and Alters Stemness-related Gene Expression in MCF7 Breast Cancer Cells
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Issued Date
2026-01-01
Resource Type
ISSN
02507005
eISSN
17917530
Scopus ID
2-s2.0-105026436657
Pubmed ID
41469131
Journal Title
Anticancer Research
Volume
46
Issue
1
Start Page
263
End Page
272
Rights Holder(s)
SCOPUS
Bibliographic Citation
Anticancer Research Vol.46 No.1 (2026) , 263-272
Suggested Citation
Suwan N., Teerawongsuwan S., Jenjittikul S., Senaweenin Y., Watanapokasin R., Rungsiwiwut R. Andrographolide Induces Mitochondrial Dysfunction and Alters Stemness-related Gene Expression in MCF7 Breast Cancer Cells. Anticancer Research Vol.46 No.1 (2026) , 263-272. 272. doi:10.21873/anticanres.17940 Retrieved from: https://hdl.handle.net/20.500.14740/55283
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Abstract
Background/Aim: Andrographolide, a compound derived from Andrographis paniculata, has exhibited promising antineoplastic effects; however, its effects on pluripotency and cancer stemness remain unclear. Since pluripotency and cancer stemness are key factors in treatment resistance and relapse, it is important to investigate how andrographolide affects these properties. Materials and Methods: MCF7 cells were treated with andrographolide (7.5-120 µM) for 24 or 48 h. Cell viability was evaluated using the MTT assay. Mitochondrial membrane potential was measured using TMRE. Gene expression of TOMM20, caspase-3, BAX, BCL2 and OCT4 was analyzed using RT-qPCR. Mammosphere and colony formation assays were performed to assess self-renewal and proliferation. Results: MTT assays revealed a dose- and time-dependent reduction in the cell viability following andrographolide treatment. TMRE staining revealed a decrease in the mitochondrial membrane potential of andrographolide-treated MCF7 cells, indicating mitochondrial dysfunction. RT-qPCR analysis showed down-regulation of TOMM20 and caspase-3 expression, although MCF7 cells are typically caspase-3 deficient. Notably, BAX expression was up-regulated following treatment with 60 µM andrographolide, suggesting the induction of apoptosis. A dose-dependent increase in OCT4 expression was observed, with a 13.52-fold rise at 60 µM, indicating a potential shift toward a pluripotent-like state. Gene correlation analysis revealed a negative correlation between TOMM20 and OCT4 expression, suggesting that TOMM20 down-regulation enhances pluripotency. The positive correlation between OCT4 and BAX expression suggests a complex link between apoptosis and stemness. Immunocytochemistry confirmed TOMM20 localization in the cytoplasm. Reduced mammosphere and colony formation indicated decreased self-renewal and proliferation. Conclusion: Andrographolide exerts anti-cancer effects through mitochondrial dysfunction and apoptosis, while paradoxically increases OCT4 expression. These findings may indicate an adaptive cellular survival mechanism, in which OCT4 up-regulation and TOMM20 down-regulation are correlated with cancer-like characteristics.