New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy
Abstract
1. Introduction
2. Enhancing Temozolomide Response with Phytochemicals
3. Strategies for the Improved Phytocompound Delivery to the Brain—The Advantages of Phyto-Nanocarriers
4. Chemical Modifications of Phytocompounds as a Way to Improve Their Solubility, Bioavailability, and Efficacy
5. Phytocompound-Based Immunotherapy
6. Phytocompounds Used as Photosensitizers in GBM Photodynamic Therapy (PDT)
7. Unraveling the Emerging Role of Less Studied Plant-Derived Substances with Anti-GBM Potential
8. Epidemiological Studies of Dietary Phytocompounds—Novel Trend in GBM Research?
9. Phytocompounds or Phytocompound-Based Products That Reached the Clinical Trials Phase in GBM Research
10. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | Group | Cell Line | Model | Results | Reference |
---|---|---|---|---|---|
Bevacizumab + elagic acid | phenolic acid | C6 | in vitro | Antiproliferative efficacy. Inhibition of MGMT expression and time-dependent inhibition of MDR1. | [27] |
5-Fluorouracil + thymoquinone | quinones | U-251MG | in vitro | Reduced cell viability and proliferation in GBM cells. Strong synergistic anticancer effect. | [28] |
Irinotekan + elagic acid | phenolic acid | C6 | in vitro | Synergistic effect. Reduced cell proliferation by inhibiting the cadherin switch and promoting the antiangiogenic processes. | [29] |
Temozolomide + berberine | alkalod | U87 U251 | in vitro/ in vivo mice | Enhanced autophagy and apoptosis in TMZ-resistant cells linked with ERK1/2 signaling. In vivo increased GBM sensitivity to TMZ through the ERK1/2 signaling pathway. | [30] |
Temozolomide + harmine | alkaloid | T98G | in vitro | Decreased cancer cells’ migration, invasion, and adhesion potentials, as well as the expression of metalloproteinases 2 and 9. | [31] |
Temozlomide + piperine | alkaloid | U251MG T98G | in vitro | Apoptosis induction by activation of caspase-8/-9/-3, MMP loss, and inhibition of cell motility. | [32] |
Temozlomide + cannabidiol | canabinoid | U87MG | in vivo mice | Controlling tumor size and improving survival. | [33] |
Temozolomide + osthol | coumarin | T98G | in vitro | Apoptosis, correlated with Bcl-2/Beclin 1 complex formation. | [34] |
Temozolomide + biohanin A | isoflavone | U251 U87 C6 | in vitro/ in vivo rats/ in silico | Enhanced cells sensitivity to TMZ in vitro and in vivo. Inhibited TMZ-induced autophagy in GBM cells by activating the AMPK/ULK1 pathway in silico. | [35] |
Temozolomide + apigenine | flavonoid | glioma cells | in vitro/ in vivo mice | Synergistic inhibition of glioma growth through the PI3K/AKT pathway. | [36] |
Temozolomide + morusin | flavonoid | U87 U251 | in vitro/ in vivo mice | Enhanced endoplasmic reticulum stress, synergistic effect in GBM cells, suppressed tumor progression in an orthotopic xenograft model. | [37] |
Temozolomide + naringenin | flavonoid | C6 U87MG LN229 HEK-293 T | in vitro/ in vivo rats | Synergistically increased efficacy of TMZ on glioma in vitro and in vivo. | [38] |
Temozolomide + xantohumol | flavonoid | U87 MG A172 | in vitro | miR-4749-5p targeting RFC2 signaling participates in XN-enhanced TMZ cytotoxicity. | [39] |
Temozolomide + honokiol | lignan | U87MG GL261 U87MG-R9 | in vitro | Significantly enhanced TMZ-induced insults. Induced greater caspase-3 activation, DNA fragmentation, cell apoptosis, and cell-cycle arrest at the G1 phase. Autophagy and consequent apoptosis in U87-MG-R9. | [40] |
Temozolomide + honokiol | lignan | U373MG GL261 U87MG | in vitro | Improved TMZ-induced insults to human malignant glioma cells. Enhanced TMZ-induced apoptosis and suppression of proliferation in human glioma cells. | [41] |
Temozolomide + magnolol | lignan | LN18 U87MG LN229 T98G HEK293 C6 | in vitro/ in vivo | Potentiation of TMZ-induced apoptosis in glioma by inhibiting NF-κB pathway-mediated MGMT activation. | [42] |
Temozoomide + elagic acid | phenolic acid | C6 | in vitro | Antiproliferative efficacy by inhibiting MGMT expression and activating apoptotic protein, p53, and caspase-3 expression. | [43] |
Temozolomide + tannic acid | phenolic acid | C6 | in vitro/ in vivo rats | Not cytotoxic to astrocytes. Induced anti-glioma activity, apoptosis, and cell-cycle arrest. Reduced the formation and size of colonies, and cell migration/adhesion. In vivo: decreased tumor volume and increased the area of intratumoral necrosis and infiltration of lymphocytes. | [44] |
Temozolomide + elagic acid | phenolic acid | C6 | in vitro | Inhibited the cadherin switch and angiogenesis. | [45] |
Temozolomide + gallic acid | phenolic acid | U87MG | in vitro | Potential augmentation of the anticancer effect of TMZ via the repression of Bcl-2 expression and Akt activation and the enhancement of the p38 MAPK pathway. | [46] |
Temozolomide + steroidal saponin (N45) | saponin | U87R | in vitro | Induced mitochondrial apoptosis, and decreased drug resistance by downregulation of NF-κB p65. | [47] |
Temozolomide + oleuropein | secoiridoid | T98G A172 | in vitro | Demonstrated additive effects that can augment the effect of TMZ. | [48] |
Temozolomide + resveratrol | stilbenoid | RG-2 LN-18 LN-428 | in vitro | Downregulated MGMT overexpression. Inhibition of the STAT3/Bcl-2/survivin signaling pathway. | [49] |
Compound/Product | ClinicalTrials.gov ID | Description | Study Type/Phase | Status |
---|---|---|---|---|
Cannabidiol | NCT05753007 | A Clinical Trial of a Hemp-Derived, High-Cannabidiol Product for Anxiety in Glioblastoma Patients | Phase 2 | Not yet recruiting |
NCT03607643 | A Study of the Efficacy of Cannabidiol in Patients with Multiple Myeloma, Glioblastoma Multiforme, and GI Malignancies | Phases 1 and 2 | Unknown status | |
TN-TC11G (Δ9-tetrahydrocannabinol + cannabidiol) | NCT03529448 | TN-TC11G (THC+CBD) Combination with Temozolomide and Radiotherapy in Patients with Newly Diagnosed Glioblastoma | Phases 1 and 2 | Recruiting |
Cannabis (for smoking) | NCT03246113 | Tolerability of Cannabis in Patients Receiving Concurrent Chemoradiation for Glioblastoma | Phase 1 | Terminated |
Sativex® (Nabiximols oromucosal spray) | NCT01812603 | A Safety Study of Sativex in Combination with Dose-Intense Temozolomide in Patients with Recurrent Glioblastoma | Phases 1 and 2 | Completed |
NCT01812616 | A Safety Study of Sativex Compared with Placebo (Both with Dose-Intense Temozolomide) in Recurrent Glioblastoma Patients | Phases 1 and 2 | Completed | |
NCT05629702 | ARISTOCRAT: Blinded Trial of Temozolomide +/− Cannabinoids | Phase 2 | Recruiting | |
Chlorogenic Acid | NCT02728349 | Tolerance and Pharmacokinetic Study of Chlorogenic Acid to Advanced Glioblastoma | Phase 1 | Completed |
Curcumin | NCT01712542 | Curcumin Bioavailability in Glioblastoma Patients | Observational | Completed |
NCT05768919 | Study of Liposomal Curcumin in Combination with RT and TMZ in Patients with Newly Diagnosed High-Grade Gliomas | Phases 1 and 2 | Recruiting |
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Majchrzak-Celińska, A.; Studzińska-Sroka, E. New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy. Molecules 2024, 29, 1682. https://doi.org/10.3390/molecules29071682
Majchrzak-Celińska A, Studzińska-Sroka E. New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy. Molecules. 2024; 29(7):1682. https://doi.org/10.3390/molecules29071682
Chicago/Turabian StyleMajchrzak-Celińska, Aleksandra, and Elżbieta Studzińska-Sroka. 2024. "New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy" Molecules 29, no. 7: 1682. https://doi.org/10.3390/molecules29071682
APA StyleMajchrzak-Celińska, A., & Studzińska-Sroka, E. (2024). New Avenues and Major Achievements in Phytocompounds Research for Glioblastoma Therapy. Molecules, 29(7), 1682. https://doi.org/10.3390/molecules29071682