Parvifloron D-based potential therapy for glioblastoma: Inducing apoptosis via the mitochondria dependent pathway

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.

Essential Oils from Côa Valley Lamiaceae Species: Cytotoxicity and Antiproliferative Effect on Glioblastoma Cells

“…Thus, these data allowed to conclude that both EOs have a dose-dependent effect, and the most likely mechanism is inducing cell death by apoptosis through DNA damage and downregulation of the cyclin-dependent kinase1 (cdk1)/cyclin B1 complex with an enhancement of p21 expression [ 11 , 71 ].…”

Unveiling the Antitumor Mechanism of 7α-Acetoxy-6β-Hydroxyroyleanone from<em> Plectranthus hadiensis</em> in Glioblastoma

“…Regarding this, terpenes, a prominent class of secondary metabolites in plants, are an example of natural compounds with enhanced therapeutic potential, including marked antitumor properties, that are worth exploring for designing future therapies for GB [13]. In addition, terpenes alluring bioactivities have already rendered them noteworthy assets across diverse industries, such as cosmetics and pharmaceuticals [10,14,22].…”

“…Half-maximal inhibitory concentration (IC50) values were further calculated using GraphPad Prism Software v.10.1.0 (GraphPad Software, Inc.) [22].…”

“…Cell death was measured using the Annexin V (AV)/PI assay by flow cytometry, as previously described [22]. Briefly, 24 h before treatment, 20×10 4 cells per well were seeded in 12-well plates.…”

An anti-glioblastoma gold(i)–NHC complex distorts mitochondrial morphology and bioenergetics to induce tumor growth inhibition

“…Increasing evidence supports the reliance of glioblastoma growth on mitochondrial functional states and OXPHOS. [38][39][40] Given the potential for three-coordinate Au(I) complexes to distort the mitochondrial structure, 9 we hypothesized that AuTri-C complexes will be effective against the mitochondria-dependent GBM. Using BT333 -a patient-derived glioblastoma cell line -we profiled the library of AuTri-C 1-6 for anticancer activity.…”