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Combining 5-ALA-PDT with berbamine as an in vitro multimodal therapy approach against bladder cancer cells
Muriel Kabus1,2, Maximilian Aumiller3,4, Adrain Rühm3,4
1Laboratory of Tumor Immunology, LIFE Center, LMU University Hospital, LMU Munich, Fraunhoferstr. 20, 82152, Planegg, Germany. Muriel.Kabus@campus.lmu.de.
Abstract:
Bladder cancer is a common urogenital malignancy that remains difficult to treat, particularly due to therapeutic resistance, such as resistance to cisplatin, in which cancer stem cells (CSCs) play a central role. This study investigates the combination of 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and berbamine as a potential multimodal treatment strategy using the bladder cancer cell lines RT112 and J82, their cisplatin-resistant variants, and generated CSC-like cells. Berbamine is a natural plant compound and was confirmed in this study to have anticancer properties by inhibiting cell migration and invasion, and by inducing apoptosis. This study also showed that berbamine enhances the accumulation of protoporphyrin IX (PpIX), the photosensitizer induced by 5-ALA. 5-ALA-PDT destroys cancer cells by stimulating PpIX via 635 nm red laser light to produce reactive oxygen species (ROS). This was found to happen in all tested cell lines, whereas berbamine could modulate the cell destruction in a concentration-dependent manner and was influenced by the specific biological characteristics of the tested cell variants. CSCs showed the strongest response to the combination therapy approach, suggesting that they may represent more vulnerable cell variants to the tested treatment. Cisplatin-resistant cell lines could also be treated successfully with 5-ALA-PDT, whereas berbamine could enhance its efficacy in the cisplatin-resistant J82 LTT. These findings suggest that the combination treatment of 5-ALA-PDT and berbamine may serve as a promising approach to overcome therapeutic resistance in bladder cancer, particularly in cisplatin-resistant and CSC-enriched tumour types.
Insights
This study shows that combining 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) with berbamine effectively targets bladder cancer, including resistant and cancer stem cells (CSCs). This combination therapy offers a promising strategy to overcome treatment resistance in bladder cancer.
Area of Science:
- Oncology
- Photomedicine
- Pharmacology
Background:
- Bladder cancer presents significant treatment challenges, especially concerning therapeutic resistance mediated by cancer stem cells (CSCs).
- Cisplatin resistance is a major hurdle in effectively treating bladder cancer.
- Cancer stem cells (CSCs) are implicated in therapeutic resistance and tumor recurrence.
Purpose of the Study:
- To investigate the efficacy of a combination therapy using 5-aminolevulinic acid-mediated photodynamic therapy (5-ALA-PDT) and berbamine against bladder cancer.
- To evaluate the impact of this combination on cisplatin-resistant bladder cancer cell lines and CSC-like cells.
- To determine if berbamine enhances the photosensitizing effects of 5-ALA-PDT.
Main Methods:
- Utilized bladder cancer cell lines (RT112, J82) and their cisplatin-resistant variants, alongside generated CSC-like cells.
- Administered 5-ALA-PDT using 635 nm red laser light to induce protoporphyrin IX (PpIX) accumulation and subsequent reactive oxygen species (ROS) generation.
- Assessed the effects of varying concentrations of berbamine on cell viability, migration, invasion, and apoptosis in conjunction with 5-ALA-PDT.
Main Results:
- Berbamine demonstrated intrinsic anticancer properties, inhibiting cell migration and invasion while inducing apoptosis.
- Berbamine enhanced PpIX accumulation, potentiating the efficacy of 5-ALA-PDT across all tested cell lines.
- Cancer stem cells (CSCs) exhibited the most significant response to the combination therapy, indicating increased vulnerability.
- The combination therapy successfully treated cisplatin-resistant cell lines, with berbamine improving 5-ALA-PDT efficacy in cisplatin-resistant J82 cells.
Conclusions:
- The combination of 5-ALA-PDT and berbamine presents a potent strategy for overcoming therapeutic resistance in bladder cancer.
- This multimodal approach is particularly promising for treating cisplatin-resistant and CSC-enriched bladder tumors.
- The findings suggest that targeting CSCs with this combination therapy could lead to improved patient outcomes.
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