Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line

Franco, Yollanda Edwirges Moreira; Okubo, Márcia Y.; Torre, Adriana de la; Paiva, Paula Pereira de; Rosa, Marcela Nunes; Silva, Viviane Aline Oliveira; Reis, Rui Manuel; Ruiz, Ana Lúcia Tasca Góis; Imamura, Paulo M.; Carvalho, João Ernesto de; Longato, Giovanna Barbarini

doi:10.3390/molecules24244498

Cited by 23 publications

(10 citation statements)

References 50 publications

(62 reference statements)

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“…The increase of PARP after CC12 treatment was consistent with our results of Br-dUTP staining, indicating the DNA fragmentation, and the higher levels of γH2AX expression induced by CC12, a symbol of DNA damage. However, not only DNA damage, the association of γH2AX and cell cycle arrest at the G1 phase was reported in GBM cells [17], which were seen in our results, too.…”

Section: Discussionsupporting

confidence: 81%

CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model

et al. 2020

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Among central nervous system tumors, glioblastoma (GBM) is the most common and the most malignant type. Even under current standard treatments, the overall survival rate is still low and the recurrence rate is high. Therefore, developing novel and effective therapy is urgently needed. CC12, a synthesized small molecule, was evaluated for the potential anti-GBM effects in two GBM cell lines, U87MG and U118MG. The observations of cell morphology, MTT assay, flow cytometry-based apoptosis after CC12 treatment, were conducted. Western blot was performed for the investigation of the apoptotic mechanism. Positron emission tomography scan analysis and bioluminescent imaging assay using a mouse xenograft model were performed for the effect of CC12 in vivo. After treated by 10 μM CC12 for 24 h, both U118MG and U87MG cells showed tumor cell death. MTT assay results showed that the survival rates decreased when the CC12 concentrations or the treatment periods increased. Ki-67 expression and flow cytometry results indicated that the proliferation was inhibited in GBM cells, and G1 phase arrest was shown. The results of 7-AAD, Br-dUTP, and JC-1 staining all showed the apoptosis of GBM cells after CC12 treatment. Increased γH2AX, caspase-3, and poly (ADP-ribose) polymerase (PARP) levels meant the DNA damage, and increased Bcl2 family proteins after CC12 treatment indicated the intrinsic apoptotic pathway was involved in CC12 induced apoptosis. Furthermore, CC12 can induce the decrease of tumor prognostic marker DcR3. In vivo experiment results showed the effect of CC12 on tumor size reduction of CC12. In addition, the ability to cross the brain–blood barrier of CC12 was also confirmed. CC12 may have anti-tumor ability through the regulation of cell cycle and apoptosis in vitro and in vivo.

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Section: Discussionsupporting

confidence: 81%

CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model

et al. 2020

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“…Elevated intracellular ROS levels mediate further upregulation of p21. ROS damages DNA, upregulating H2A family member X (H2AX) and consequently p21, as evidenced after Coronarin D, CP, and McC1 treatment [36,47]. As CDKNs, p21 and p27 inhibit specific cyclin-CDK complexes that are necessary for cell cycle progression.…”

Section: Cell Cyclementioning

confidence: 99%

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Zhai

Siddiqui

Abdellatif

et al. 2021

Cancers

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Glioblastoma (GBM) is an aggressive, often fatal astrocyte-derived tumor of the central nervous system. Conventional medical and surgical interventions have greatly improved survival rates; however, tumor heterogeneity, invasiveness, and chemotherapeutic resistance continue to pose clinical challenges. As such, dietary natural substances—an integral component of the lifestyle medicine approach to chronic diseases—are examined as potential chemotherapeutic agents. These heterogenous substances exert anti-GBM effects by upregulating apoptosis and autophagy, inducing cell cycle arrest, interfering with tumor metabolism, and inhibiting proliferation, neuroinflammation, chemoresistance, angiogenesis, and metastasis. Although these beneficial effects are promising, natural substances’ efficacy in GBM is constrained by their bioavailability and blood–brain barrier permeability; various chemical formulations are proposed to improve their pharmacological properties. Many of the reviewed substances are available as over-the-counter dietary supplements, underscoring their viability as lifestyle interventions. However, clinical trials remain necessary to substantiate the in vitro and in vivo properties of natural substances.

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“…Using the absorbance values, the cell growth (%) for each cell line, at each sample concentration, was calculated considering at 100% of cell growth the difference between the absorbances of untreated cells after 48 h incubation (T1) and at the sample addition moment (T0). The curve cell growth vs. sample concentration was plotted and GI 50 (concentration required for 50% growth inhibition) was calculated by sigmoidal regression using the Origin 8.0 software (OriginLab Corporation, Northampton, MA, USA) [ 36 ].…”

Section: Methodsmentioning

confidence: 99%

Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies

et al. 2020

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Multidrug resistance (MDR) is the main obstacle in anticancer therapy. The use of drug combinations to circumvent tumor resistance is a well-established principle in the clinic. Among the therapeutic targets, glycoprotein-P (P-gp), an energy-dependent transmembrane efflux pump responsible for modulating MDR, is highlighted. Many pharmacological studies report the ability of calcium channel blockers to reverse tumor resistance to chemotherapy drugs. Isolated for the first time from parsley, the phenylpropanoid apiole is described as a potent calcium channel inhibitor. Taking this into account, herein, the ability of apiole to potentiate the action of well-established chemotherapeutics in the clinic, as well as the compound’s relationship with the reversal of the resistance phenomenon by blocking P-gp, is reported. The association of apiole with both chemotherapeutic drugs doxorubicin and vincristine resulted in synergistic effect, in a concentration-dependent manner, as evaluated by the concentration reduction index. Molecular docking analysis demonstrated the affinity between apiole and the active site of P-gp, corroborating the inhibitory effect. Moreover, apiole demonstrated druglikeness, according to ADME analysis. In conclusion, apiole possibly blocks the active P-gp site, with strong binding energy, which, in turn, inhibits doxorubicin and vincristine efflux, increasing the antiproliferative response of these chemotherapeutic agents.

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Coronarin D Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Line

Cited by 23 publications

References 50 publications

CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model

CC12 Induces Apoptotic Cell Death and Cell Cycle Arrest in Human Glioblastoma Cell Lines and Mouse Xenograft Model

Natural Compounds in Glioblastoma Therapy: Preclinical Insights, Mechanistic Pathways, and Outlook

Reversal of Ovarian Cancer Cell Lines Multidrug Resistance Phenotype by the Association of Apiole with Chemotherapies

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