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Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway
Mariana Magalhães1,2,3,4, Eva María Domínguez-Martín5,6, Joana Jorge7,8
1PhD Programme in Experimental Biology and Biomedicine, Institute for Interdisciplinary Research (IIIUC), University of Coimbra, Coimbra, Portugal.
Abstract:
Glioblastoma (GB) is the most malignant and frequent primary tumor of the central nervous system. The lack of diagnostic tools and the poor prognosis associated with this tumor type leads to restricted and limited options of treatment, namely surgical resection and radio-chemotherapy. However, despite these treatments, in almost all cases, patients experience relapse, leading to survival rates shorter than 5 years (∼15-18 months after diagnosis). Novel therapeutic approaches are urgently required (either by discovering new medicines or by repurposing drugs) to surpass the limitations of conventional treatments and improve patients' survival rate and quality of life. In the present work, we investigated the antitumor potential of parvifloron D (ParvD), a drug lead of natural origin, in a GB cell line panel. This natural drug lead induced G2/M cell cycle arrest and apoptosis via activation of the intrinsic mitochondria-dependent pathway. Moreover, the necessary doses of ParvD to induce pronounced inhibitory effects were substantially lower than that of temozolomide (TMZ, first-line treatment) required to promote comparable effects. Therefore, ParvD may have the potential to overcome the resistance related to TMZ and contribute to the pursuit of hopeful treatments based on ParvD as a drug lead for future chemotherapeutics.
Insights
Parvifloron D, a natural compound, shows promise against glioblastoma by inducing cell cycle arrest and apoptosis. It may overcome resistance to temozolomide, offering a potential new therapeutic avenue.
Area of Science:
- Neuro-oncology
- Natural Product Chemistry
- Cancer Therapeutics
Background:
- Glioblastoma (GB) is the most aggressive primary brain tumor with limited treatment options and poor prognosis.
- Conventional treatments like surgery, radio-chemotherapy often lead to relapse and short survival rates.
- Novel therapeutic strategies are crucial to improve glioblastoma patient outcomes.
Purpose of the Study:
- To investigate the anti-glioblastoma potential of parvifloron D (ParvD), a natural compound.
- To evaluate ParvD's efficacy in glioblastoma cell lines.
- To compare ParvD's effectiveness with temozolomide (TMZ), the current first-line treatment.
Main Methods:
- Screening of parvifloron D in a panel of glioblastoma cell lines.
- Assessment of cell cycle progression and apoptosis induction.
- Comparative dose-response analysis against temozolomide.
Main Results:
- Parvifloron D induced G2/M cell cycle arrest and apoptosis in glioblastoma cells.
- The mechanism of action involves the intrinsic mitochondria-dependent pathway.
- Effective doses of ParvD were significantly lower than those of temozolomide for comparable effects.
Conclusions:
- Parvifloron D exhibits significant antitumor activity against glioblastoma.
- ParvD demonstrates potential to overcome temozolomide resistance.
- ParvD represents a promising drug lead for developing novel glioblastoma chemotherapeutics.
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