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Exploring the cytotoxicity and anticancer effects of doxycycline and azithromycin on human glioblastoma multiforme
Siti Nazihahasma Hassan1,2, Abdul Aziz Mohamed Yusoff1,2,3, Zamzuri Idris1,2
1Department of Neurosciences, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian Kelantan, Malaysia.
Background:
Previous studies had reported on the cytotoxic activities of generic antibiotics such as doxycycline (DOXY) and azithromycin (AZI) in multiple types of human cancers. Given that resistance to standard anti-glioblastoma multiforme (GBM) drug [temozolomide (TMZ)] is common and inevitable, alternative candidates are greatly needed.
Purpose And Method:
The present study was undertaken to explore the cytotoxicity and anticancer effects of DOXY and AZI on human GBM U87 cells via 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), Hoechst, Annexin V-FITC/PI, and clonogenic assays. CompuSyn software was used to determine the combination index (CI) for DOXY+AZI.
Result:
Individual treatment with DOXY and AZI decreased U87 cell viability in dose- and time-dependent, and quantitatively comparable to TMZ. Nevertheless, combinations of both antibiotics evidenced antagonistic behaviour in U87 cells. Increased apoptotic event was also observed with the individual treatment of DOXY and AZI. Furthermore, the proliferative and clonogenic capability of 21-day survived U87 cells was completely terminated by DOXY and AZI, but not TMZ.
Conclusion:
The antiproliferative and apoptosis-inducing activity exhibited by both antibiotics against U87 cells demonstrates their potential as a likely alternative to combat GBM. It would be interesting to find out more about their molecular players and cytotoxic effects in different types of GBM cells, including glioma stem cells (GSCs).
Insights
Doxycycline and azithromycin show promise as glioblastoma treatments, effectively reducing cancer cell viability and proliferation. These antibiotics offer a potential alternative for glioblastoma multiforme (GBM) therapy, especially where drug resistance is a concern.
Area of Science:
- Oncology
- Pharmacology
- Cell Biology
Background:
- Doxycycline (DOXY) and azithromycin (AZI) exhibit cytotoxic activities in various human cancers.
- Temozolomide (TMZ) resistance is common in glioblastoma multiforme (GBM), necessitating alternative therapeutic agents.
Purpose of the Study:
- To investigate the cytotoxicity and anticancer effects of DOXY and AZI on human GBM U87 cells.
- To evaluate the combined effects of DOXY and AZI using CompuSyn software.
Main Methods:
- Cell viability assessed using MTT assay.
- Apoptosis evaluated via Hoechst and Annexin V-FITC/PI staining.
- Clonogenic assays determined long-term cell survival and proliferation.
Main Results:
- Both DOXY and AZI individually reduced U87 cell viability comparable to TMZ.
- Combined DOXY and AZI treatment showed antagonistic effects.
- Individual DOXY and AZI treatments induced apoptosis and terminated proliferative/clonogenic potential in surviving cells.
Conclusions:
- DOXY and AZI demonstrate antiproliferative and apoptosis-inducing potential against GBM U87 cells.
- These antibiotics represent a potential alternative for GBM treatment.
- Further research into molecular mechanisms and efficacy in diverse GBM cell types, including glioma stem cells (GSCs), is warranted.
