Curcumin potentiates the antitumor activity of Paclitaxel in rat glioma C6 cells

Fratantonio, Deborah; Molonia, Maria Sofia; Bashllari, Romina; Muscarà, Claudia; Ferlazzo, Guido; Costa, Guilherme; Saija, A.; Cimino, Francesco; Speciale, Antonio

doi:10.1016/j.phymed.2018.08.009

Cited by 41 publications

(23 citation statements)

References 33 publications

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“…Furthermore, curcumin sensitizes GSCs to several chemo- and radio-therapeutic agents due to its ability to modulate different cell signaling, beyond ATG [ 18 , 45 , 89 , 95 , 96 , 97 , 98 ]. In fact, when administered in combination with currently used therapies, curcumin further potentiates their anti-tumor activity against GBM [ 19 , 99 , 100 , 101 ]. For instance, curcumin enhances temozolomide (TMZ)-induced cytotoxicity by disputing the Akt/mTOR pathway in U87MG cell lines, thereby overcoming GBM therapeutic resistance [ 18 ].…”

Section: Curcumin Suppresses Gscs’ Tumorigenicity Through Atg Indumentioning

confidence: 99%

“…In vitro studies, using both human (T98G, U87MG, T67, U373) and rat (C6) GBM cell lines, demonstrated that curcumin and curcuminoids (i.e., demethoxycurcumin (DMC)) reduce cell survival through the suppression of both NF-κB and AP-1 signaling activation. This prevents the constitutive activation of Akt and JNK [ 45 , 100 , 101 , 123 , 124 ]. At the same time, the curcumin-dependent inhibition of AP-1 signaling suppresses MMPs transcription, thus markedly repressing GBM cells invasive potential [ 122 ].…”

Section: Effects Of Curcumin On Gbm Beyond Atg Inductionmentioning

confidence: 99%

“…These results are in line with research reports demonstrating that the curcumin-dependent suppression of MMP-9 promoter activity occurs via the inhibition of NF-κB and AP-1 DNA binding activities [ 125 ]. Furthermore, the inhibition of NF-κB signaling with curcumin potentiates the anti-tumor effects against GBM of different therapeutic agents such as the alkylating agent nimustine hydrochloride (ACNU) [ 101 ] and the microtubule-stabilizing agent paclitaxel (PTX) [ 100 ].…”

Section: Effects Of Curcumin On Gbm Beyond Atg Inductionmentioning

confidence: 99%

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The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

et al. 2020

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The present review focuses on the multi-faceted effects of curcumin on the neurobiology glioblastoma multiforme (GBM), with a special emphasis on autophagy (ATG)-dependent molecular pathways activated by such a natural polyphenol. This is consistent with the effects of curcumin in a variety of experimental models of neurodegeneration, where the molecular events partially overlap with GBM. In fact, curcumin broadly affects various signaling pathways, which are similarly affected in cell degeneration and cell differentiation. The antitumoral effects of curcumin include growth inhibition, cell cycle arrest, anti-migration and anti-invasion, as well as chemo- and radio-sensitizing activity. Remarkably, most of these effects rely on mammalian target of rapamycin (mTOR)-dependent ATG induction. In addition, curcumin targets undifferentiated and highly tumorigenic GBM cancer stem cells (GSCs). When rescuing ATG with curcumin, the tumorigenic feature of GSCs is suppressed, thus counteracting GBM establishment and growth. It is noteworthy that targeting GSCs may also help overcome therapeutic resistance and reduce tumor relapse, which may lead to a significant improvement of GBM prognosis. The present review focuses on the multi-faceted effects of curcumin on GBM neurobiology, which represents an extension to its neuroprotective efficacy.

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Section: Curcumin Suppresses Gscs’ Tumorigenicity Through Atg Indumentioning

confidence: 99%

Section: Effects Of Curcumin On Gbm Beyond Atg Inductionmentioning

confidence: 99%

Section: Effects Of Curcumin On Gbm Beyond Atg Inductionmentioning

confidence: 99%

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The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

et al. 2020

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“…Glioblastoma multiforme (GBM) is the most aggressive, invasive, and undifferentiated type of central nervous system tumor in adults [1]. Although several treatment options are available, including surgery along with adjuvant chemo- and radio-therapy, the disease has a poor prognosis, with a median survival rate of 12–17 months.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the Effect of Native 1,4-Naphthoquinones Plumbagin, Menadione, and Lawsone on Viability, Redox Status, and Mitochondrial Functions of C6 Glioblastoma Cells

et al. 2019

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Background: 1,4-naphthoquinones, especially juglone, are known for their anticancer activity. However, plumbagin, lawsone, and menadione have been less investigated for these properties. Therefore, we aimed to determine the effects of plumbagin, lawsone, and menadione on C6 glioblastoma cell viability, ROS production, and mitochondrial function. Methods: Cell viability was assessed spectrophotometrically using metabolic activity method, and by fluorescent Hoechst/propidium iodide nuclear staining. ROS generation was measured fluorometrically using DCFH-DA. Oxygen uptake rates were recorded by the high-resolution respirometer Oxygraph-2k. Results: Plumbagin and menadione displayed highly cytotoxic activity on C6 cells (IC50 is 7.7 ± 0.28 μM and 9.6 ± 0.75 μM, respectively) and caused cell death by necrosis. Additionally, they increased the amount of intracellular ROS in a concentration-dependent manner. Moreover, even at very small concentrations (1–3 µM), these compounds significantly uncoupled mitochondrial oxidation from phosphorylation impairing energy production in cells. Lawsone had significantly lower viability decreasing and mitochondria-uncoupling effect, and exerted strong antioxidant activity. Conclusions: Plumbagin and menadione exhibit strong prooxidant, mitochondrial oxidative phosphorylation uncoupling and cytotoxic activity. In contrast, lawsone demonstrates a moderate effect on C6 cell viability and mitochondrial functions, and possesses strong antioxidant properties.

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“…The results of its migration experiment also verify this (Figure 4). In addition, it may be that PTX and curcumin produce synergistic anti-cancer effects 37. From the experimental results, PTX and curcumin exert potent anti-ovarian cancer effects in vitro and can help reduce dosage and minimize side effects of cytotoxic therapies.…”

Section: Discussionmentioning

confidence: 99%

<p>Co-Delivery of Curcumin and Paclitaxel by “Core-Shell” Targeting Amphiphilic Copolymer to Reverse Resistance in the Treatment of Ovarian Cancer</p>

Zhao

Chen

et al. 2019

IJN

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Background: Ovarian cancer is a common malignancy in the female reproductive system with a high mortality rate. The most important reason is multidrug resistance (MDR) of cancer chemotherapy. To reduce side effects, reverse resistance and improve efficacy for the treatment of ovarian cancer, a "core-shell" polymeric nanoparticle-mediated curcumin and paclitaxel co-delivery platform was designed. Methods: Nuclear magnetic resonance confirmed the successful grafting of polyethylenimine (PEI) and stearic acid (SA) (PEI-SA), which is designed as a mother core for transport carrier. Then, PEI-SA was modified with hyaluronic acid (HA) and physicochemical properties were examined. To understand the regulatory mechanism of resistance and measure the anti-tumor efficacy of the treatments, cytotoxicity assay, cellular uptake, P-glycoprotein (P-gp) expression and migration experiment of ovarian cancer cells were performed. In addition, adverse reactions of nanoformulation to the reproductive system were examined. Results: HA-modified drug-loaded PEI-SA had a narrow size of about 189 nm in diameters, and the particle size was suitable for endocytosis. The nanocarrier could target specifically to CD44 receptor on the ovarian cancer cell membrane. Co-delivery of curcumin and paclitaxel by the nanocarriers exerts synergistic anti-ovarian cancer effects on chemosensitive human ovarian cancer cells (SKOV3) and multi-drug resistant variant (SKOV3-TR30) in vitro, and it also shows a good anti-tumor effect in ovarian tumor-bearing nude mice. The mechanism of reversing drug resistance may be that the nanoparticles inhibit the efflux of P-gp, inhibit the migration of tumor cells, and curcumin synergistically reverses the resistance of PTX to increase antitumor activity. It is worth noting that the treatment did not cause significant toxicity to the uterus and ovaries with the observation of macroscopic and microscopic. Conclusion: This special structure of targeting nanoparticles co-delivery with the curcumin and paclitaxel can increase the anti-tumor efficacy without increasing the adverse reactions as a promising strategy for therapy ovarian cancer.

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Curcumin potentiates the antitumor activity of Paclitaxel in rat glioma C6 cells

Cited by 41 publications

References 33 publications

The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

The Multi-Faceted Effect of Curcumin in Glioblastoma from Rescuing Cell Clearance to Autophagy-Independent Effects

Comparison of the Effect of Native 1,4-Naphthoquinones Plumbagin, Menadione, and Lawsone on Viability, Redox Status, and Mitochondrial Functions of C6 Glioblastoma Cells

<p>Co-Delivery of Curcumin and Paclitaxel by “Core-Shell” Targeting Amphiphilic Copolymer to Reverse Resistance in the Treatment of Ovarian Cancer</p>

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