β-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells

Dias, Rosane Borges; Araújo, Taís Bacelar Sacramento de; Freitas, Roseli Santos de; Rodrigues, Ana Carolina Borges da Cruz; Sousa, Letícia Palmeira; Sales, Caroline Brandi Schlaepfer; Valverde, Ludmila de Faro; Soares, Milena Botelho Pereira; Reis, Mitermayer Galvão dos; Coletta, Ricardo D.; Ramos, Eduardo Antônio Gonçalves; Câmara, Celso A.; Silva, Tânia Maria Sarmento; Barbosa-Filho, José Maria; Bezerra, Daniel P.; Rocha, Clarissa Araújo Gurgel

doi:10.1016/j.freeradbiomed.2018.07.022

Cited by 24 publications

(19 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Blood collection (5 mL) was performed in heparinized vials by trained professionals at the Laboratory of Tissue Engineering and Immunopharmacology (LETI, IGM-FIOCRUZ, Salvador, Brazil), using sterile disposable syringes. PBMCs were isolated by a standard protocol described by Dias et al (2018) [ 6 ]. The institutional review board of the Gonçalo Moniz Institution, Oswaldo Cruz Foundation (IGM-FIOCRUZ), in Salvador, Bahia, Brazil, approved all experimental protocols (No.031019/2013).…”

Section: Methodsmentioning

confidence: 99%

“…The high morbidity and mortality of OSCC occurs mainly due to late diagnosis, contributing to a high rate of metastatic cases. Moreover, limited knowledge concerning this tumor’s biology has led to a consequent lack of potential target molecules that may direct more effective therapeutic strategies [ 6 , 7 ]. Thus, achieving a fuller understanding of the biological processes underlying treatment effectiveness and the development of metastasis is essential to the success of intervention strategies.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells

Araújo

Rocha

Vidal

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Due to its importance in the pathogenesis of oral squamous cell carcinoma (OSCC), the Hedgehog (HH) pathway is considered a potential therapeutic target. We investigated the effects of GANT61, a GLI inhibitor, on HH gene expression, as well as on metastatic OSCC cell proliferation and death. Following culture in DMEM medium, cytotoxicity of GANT61 against different tumor and non-tumor cell types was assessed by alamarBlue assays. Cytotoxicity analysis revealed that the metastatic HSC3 cell line was the most sensitive (IC50: 36 µM) to the tested compound. The compound’s effects on the expression of HH pathways components were analyzed by qPCR and Western blot; cell viability was analyzed by trypan blue assay and flow cytometry were used to investigate cell cycle phase, morphology, and death patterns in HSC3 cells. A significant reduction in mRNA levels of the GLI1 transcription factor was found after 12 h of treatment withGANT61. Protein expression levels of other HH pathway components (PTCH1, SHH, and Gli1) and HSC3 cell viability also decreased after 24 h of treatment. Cell cycle analysis and death pattern evaluations revealed significantly increased nuclear fragmentation in sub-G1 phase, as well as cell death due to apoptosis. In conclusion, the significantly reduced GLI1 gene expression seen in response to the GLI inhibitor indicates diminished downstream activation in HH pathway components. GANT61 significantly reduced cell viability in the metastatic cell line of OSCC and promoted a significant increase in nuclear fragmentation and cell death by apoptosis.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells

Araújo

Rocha

Vidal

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…The alamar blue assay was used to quantify the cell viability and was performed following the procedure that was previously described [38] , [39] , [40] . Negative controls received the vehicle that was used for diluting the compound tested.…”

Section: Methodsmentioning

confidence: 99%

A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells

et al. 2019

View full text Add to dashboard Cite

Piplartine (piperlongumine) is a plant-derived compound found in some Piper species that became a novel potential antineoplastic agent. In the present study, we synthesized a novel platinum complex containing a piplartine derivative cis-[PtCl(PIP-OH)(PPh3)2]PF6 (where, PIP-OH = piplartine demethylated derivative; and PPh3 = triphenylphosphine) with enhanced cytotoxicity in different cancer cells, and investigated its apoptotic action in human promyelocytic leukemia HL-60 cells. The structure of PIP-OH ligand was characterized by X-ray crystallographic analysis and the resulting platinum complex was characterized by infrared, molar conductance measurements, elemental analysis and NMR experiments. We found that the complex is more potent than piplartine in a panel of cancer cell lines. Apoptotic cell morphology, increased internucleosomal DNA fragmentation, without cell membrane permeability, loss of the mitochondrial transmembrane potential, increased phosphatidylserine externalization and caspase-3 activation were observed in complex-treated HL-60 cells. Treatment with the complex also caused a marked increase in the production of reactive oxygen species (ROS), and the pretreatment with N-acetyl-L-cysteine, an antioxidant, reduced the complex-induced apoptosis, indicating activation of ROS-mediated apoptosis pathway. Important, pretreatment with a p38 MAPK inhibitor (PD 169316) and MEK inhibitor (U-0126), known to inhibit ERK1/2 activation, also prevented the complex-induced apoptosis. The complex did not induce DNA intercalation in cell-free DNA assays. In conclusion, the complex exhibits more potent cytotoxicity than piplartine in a panel of different cancer cells and triggers ROS/ERK/p38-mediated apoptosis in HL-60 cells.

show abstract

“…For example, erufosine is able to induce ROS in OSCC cell lines and the loss of mitochondrial membrane potential [ 42 ]. β-lapachone produces reactive oxygen species-mediated apoptosis in human OSCC cells [ 6 ]. In addition, recent studies demonstrated that soft coral compounds mediate ROS induced apoptosis and DNA damage in OSCC cells in vitro [ 7 , 13 ].…”

Section: Discussionmentioning

confidence: 99%

“…The accumulation of DNA damage resulting from incomplete repair or disrepair may lead to DNA lesion, mutagenesis and consequently cancerous transform generation [ 5 ]. Several natural compounds targeting ROS has been reported to regulate apoptosis for selective killing in oral cancer [ 6 , 7 , 8 , 9 ]. Thus, the reduction of ROS might play a critical role in regulating the selective activation of apoptosis for selective killing in oral cancer chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

Sandensolide Induces Oxidative Stress-Mediated Apoptosis in Oral Cancer Cells and in Zebrafish Xenograft Model

Chen

Liu

et al. 2018

Marine Drugs

View full text Add to dashboard Cite

Presently, natural sources and herbs are being sought for the treatment of human oral squamous cell carcinoma (OSCC) in order to alleviate the side effects of chemotherapy. This study investigates the effect of sandensolide, a cembrane isolated from Sinularia flexibilis, to inhibit human OSCC cell growth with the aim of developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (Ca9.22, SCC9 and HSC-3 cell lines) and oral normal cells (HGF-1), as well as a zebrafish xenograft model, were used to test the cytotoxicity of sandensolide (MTT assay), as well as to perform cell cycle analysis and Western blotting. Both the in vitro bioassay and the zebrafish xenograft model demonstrated the anti-oral cancer effect of sandensolide. Moreover, sandensolide was able to significantly suppress colony formation and induce apoptosis, as well as cell cycle arrest, in OSCC by regulating multiple key proteins. Induction of reactive oxygen species (ROS) was observed in sandensolide-treated oral cancer cells. However, these apoptotic changes were rescued by NAC pretreatment. These findings contribute to the knowledge of the model of action of sandensolide, which may induce oxidative stress-mediated cell death pathways as a potential agent in oral cancer therapeutics.

show abstract

β-Lapachone and its iodine derivatives cause cell cycle arrest at G2/M phase and reactive oxygen species-mediated apoptosis in human oral squamous cell carcinoma cells

Cited by 24 publications

References 43 publications

GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells

GANT61 Reduces Hedgehog Molecule (GLI1) Expression and Promotes Apoptosis in Metastatic Oral Squamous Cell Carcinoma Cells

A novel platinum complex containing a piplartine derivative exhibits enhanced cytotoxicity, causes oxidative stress and triggers apoptotic cell death by ERK/p38 pathway in human acute promyelocytic leukemia HL-60 cells

Sandensolide Induces Oxidative Stress-Mediated Apoptosis in Oral Cancer Cells and in Zebrafish Xenograft Model

Contact Info

Product

Resources

About