Arsenic trioxide and BIBR1532 synergistically inhibit breast cancer cell proliferation through attenuation of NF-κB signaling pathway

Nasrollahzadeh, Ali; Bashash, Davood; Kabuli, Majid; Zandi, Zahra; Kashani, Bahareh; Zaghal, Azam; Mousavi, Seyed Asadollah; Ghaffari, Seyed H.

doi:10.1016/j.lfs.2020.118060

Cited by 22 publications

(19 citation statements)

References 33 publications

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“… 455 Therefore, this group used the hTERT inhibitor BIBR1532, combined with ATO, to make cells sensitive at a low concentration of ATO, which could synergistically inhibit the survival, proliferation, and accelerated apoptosis of breast cancer cells. 455 …”

Section: Combination Therapy Of Targeted Small-molecule Compounds In ...mentioning

confidence: 99%

“…454 In addition, it was reported that arsenic trioxide (ATO) could induce apoptosis of breast cancer cells at high concentrations, but it was easy to cause side effects. 455 Therefore, this group used the hTERT inhibitor BIBR1532, combined with ATO, to make cells sensitive at a low concentration of ATO, which could synergistically inhibit the survival, proliferation, and accelerated apoptosis of breast cancer cells. 455 Targeted drug combination therapy is a prospective clinical therapeutic strategy that could induce apoptosis and autophagic cell death by regulating some targeted proteins and signaling pathways.…”

Section: Combination Therapy Of Targeted Small-molecule Compounds In ...mentioning

confidence: 99%

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Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Liao

Qin

et al. 2022

Sig Transduct Target Ther

302

154

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Regulated cell death (RCD), also well-known as programmed cell death (PCD), refers to the form of cell death that can be regulated by a variety of biomacromolecules, which is distinctive from accidental cell death (ACD). Accumulating evidence has revealed that RCD subroutines are the key features of tumorigenesis, which may ultimately lead to the establishment of different potential therapeutic strategies. Hitherto, targeting the subroutines of RCD with pharmacological small-molecule compounds has been emerging as a promising therapeutic avenue, which has rapidly progressed in many types of human cancers. Thus, in this review, we focus on summarizing not only the key apoptotic and autophagy-dependent cell death signaling pathways, but the crucial pathways of other RCD subroutines, including necroptosis, pyroptosis, ferroptosis, parthanatos, entosis, NETosis and lysosome-dependent cell death (LCD) in cancer. Moreover, we further discuss the current situation of several small-molecule compounds targeting the different RCD subroutines to improve cancer treatment, such as single-target, dual or multiple-target small-molecule compounds, drug combinations, and some new emerging therapeutic strategies that would together shed new light on future directions to attack cancer cell vulnerabilities with small-molecule drugs targeting RCD for therapeutic purposes.

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Section: Combination Therapy Of Targeted Small-molecule Compounds In ...mentioning

confidence: 99%

Section: Combination Therapy Of Targeted Small-molecule Compounds In ...mentioning

confidence: 99%

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Liao

Qin

et al. 2022

Sig Transduct Target Ther

302

154

View full text Add to dashboard Cite

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“…Moreover, independently from its activity as functional telomerase inhibitor, BIBR1532 induces the down-regulation of TERT expression, which in turn further weakens TA and provides additional anti-cancer effects linked to impairment of its extra-telomeric functions (8,12). In addition, BIBR1532 displayed potential efficacy as adjuvant in combination with other anti-cancer agents and radiotherapy in lung and breast cancer as well as acute promyelocytic leukemia (13)(14)(15). Therefore, BIBR1532 may be potentially an ideal compound for cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

The Small Molecule BIBR1532 Exerts Potential Anti-cancer Activities in Preclinical Models of Feline Oral Squamous Cell Carcinoma Through Inhibition of Telomerase Activity and Down-Regulation of TERT

et al. 2021

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Expression of telomerase reverse transcriptase (TERT) and telomerase activity (TA) is a main feature of cancer, contributing to cell immortalization by causing telomeres dysfunction. BIBR1532 is a potent telomerase inhibitor that showed potential anti-tumor activities in several types of cancer, by triggering replicative senescence and apoptosis. In a previous work, we detected, for the first time, TERT expression and TA in preclinical models of feline oral squamous cell carcinoma (FOSCC); therefore, we aimed at extending our investigation by testing the effects of treatment with BIBR1532, in order to explore the role of telomerase in this tumor and foreshadow the possibility of it being considered as a future therapeutic target. In the present study, treatment of FOSCC cell lines SCCF1, SCCF2, and SCCF3 with BIBR1532 resulted in successful inhibition of TA, with subsequent cell growth stoppage and decrease in cell viability. Molecular data showed that up-regulation of cell cycle inhibitor p21, unbalancing of Bax/Bcl-2 ratio, and down-regulation of survival gene Survivin were mostly involved in the observed cellular events. Moreover, BIBR1532 diminished the expression of TERT and its transcriptional activator cMyc, resulting in the down-regulation of epidermal growth factor receptor (EGFR), phospho-ERK/ERK ratio, and matrix metalloproteinases (MMPs)-1/-2 and−9, likely as a consequence of an impairment of TERT extra-telomeric functions. Taken together, our data suggest that BIBR1532 exerts multiple anti-cancer activities in FOSCC by inhibiting telomerase pathway and interfering with signaling routes involved in cell proliferation, cell survival, and invasion, paving the way for future translational studies aimed at evaluating its possible employment in the treatment of this severe tumor of cats.

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“…Therefore, the limited success of ATO as a single agent at a clinical dose of 0.5-2 µM in GBM has generated a great deal of interest in using ATO in combination with other anticancer agents to enhance its antitumor properties (10,11). For instance, we have previously indicated that telomerase inhibition using BIBR1532 sensitizes breast cancer cells to low concentrations of ATO (24). In the case of GBM, erlotinib, an inhibitor of epidermal growth factor receptor (EGFR), has been found to enhance the cytotoxic effects of ATO (25).…”

Section: Discussionmentioning

confidence: 99%

Blockade of Nuclear Factor-Κb (NF-Κb) Pathway Using Bay 11-7082 Enhances Arsenic Trioxide-Induced Antiproliferative Activity in U87 Glioblastoma Cells

et al. 2022

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Background: Glioblastoma (GBM), the most aggressive and common form of glioma, accounts for over 13,000 death per year in the United States which indicates the importance of developing novel strategies for the treatment of this fatal malignancy. Although Arsenic trioxide (ATO) hinders the growth and survival of GBM cells, the requirement of concentrations higher than 4 µM for triggering apoptotic cell death has questioned its safety profile. Since the NF-κB signaling pathway plays a crucial role in tumorigenesis and chemo-resistance, targeting this oncogenic pathway may sensitize GBM cells to lower concentrations of ATO. Methods: Anti-tumor effects of ATO as monotherapy and in combination with Bay 11-7082 were determined using MTT, crystal violet staining, Annexin V/PI staining and scratch assays. Quantitative reverse transcription-PCR (qRT-PCR) analysis was applied to elucidate the molecular mechanisms underlying the anti-tumor activity of this combination therapy. Results: Our results revealed that ATO and Bay 11-7082 synergistically inhibited the proliferation and survival of GBM cells. Also, it was revealed that NF-κB inhibition using Bay 11-7082 enhanced the inhibitory effects of ATO on migration of GBM cells via suppressing the expression of NF-κB target genes such as TWIST, MMP2, ICAM-1, and cathepsin B. Furthermore, combination treatment of GBM cells with ATO and Bay 11-7082 significantly induce apoptotic cell death coupled with downregulation of NF-κB anti-apoptotic target genes including Bcl-2 and IAP family members. Conclusions: Altogether, these findings suggest that combination therapy with ATO and Bay 11-7082 may be a promising strategy for the treatment of GBM.

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Arsenic trioxide and BIBR1532 synergistically inhibit breast cancer cell proliferation through attenuation of NF-κB signaling pathway

Cited by 22 publications

References 33 publications

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

Regulated cell death (RCD) in cancer: key pathways and targeted therapies

The Small Molecule BIBR1532 Exerts Potential Anti-cancer Activities in Preclinical Models of Feline Oral Squamous Cell Carcinoma Through Inhibition of Telomerase Activity and Down-Regulation of TERT

Blockade of Nuclear Factor-Κb (NF-Κb) Pathway Using Bay 11-7082 Enhances Arsenic Trioxide-Induced Antiproliferative Activity in U87 Glioblastoma Cells

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