Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL‑60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells

Chen, Jing; Wei, Hulai; Cheng, Jie; Xie, Baohua; Wang, Bei; Yi, Juan; Tian, Baoying; Liu, Zhuan; Wang, Feifei; Zhang, Zhewen

doi:10.3892/ol.2017.7353

Cited by 16 publications

(18 citation statements)

References 31 publications

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“…demonstrated that As 2 O 3 could be highly effective in the treatment of acute promyelocytic leukemia (APL), and increasing studies have shown that it can induce complete remission, even in patients with relapsed APL, at low doses and with minimal general toxicity [ 8 ]. In other studies, As 2 O 3 has been shown to exert cytotoxic effects on a variety of tumors, such as lung cancer [ 9 ], nasopharyngeal carcinoma [ 10 ], osteosarcoma [ 11 ], neurogliocytoma [ 12 ], hepatoma [ 13 ], cervical cancer [ 14 ], cholangiocarcinoma [ 15 ], breast cancer [ 16 ], gastric cancer [ 17 ] and ovarian cancer [ 18 ]. These effects have been documented in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Xiong

Liu

et al. 2018

Biol Res

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BackgroundArsenic trioxide (As2O3), a drug that has been used in China for approximately two thousand years, induces cell death in a variety of cancer cell types, including neuroblastoma (NB). The tyrosine kinase receptor (Trk) family comprises three members, namely TrkA, TrkB and TrkC. Various studies have confirmed that TrkA and TrkC expression is associated with a good prognosis in NB, while TrkB overexpression can lead to tumor cell growth and invasive metastasis. Previous studies have shown that As2O3 can inhibit the growth and proliferation of a human NB cell line and can also affect the N-Myc mRNA expression. It remains unclear whether As2O3 regulates Trks for the purposes of treating NB.MethodsThe aim of the present study was to investigate the effect of As2O3 on Trk expression in NB cell lines and its potential therapeutic efficacy. SK-N-SH cells were grown with increasing doses of As2O3 at different time points. We cultured SK-N-SH cells, which were treated with increasing doses of As2O3 at different time points. Trk expression in the NB samples was quantified by immunohistochemistry, and the cell cycle was analyzed by flow cytometry. TrkA, TrkB and TrkC mRNA expression was evaluated by real-time PCR analysis.ResultsImmunohistochemical and real-time PCR analyses indicated that TrkA and TrkC were over-expressed in NB, and specifically during stages 1, 2 and 4S of the disease progression. TrkB expression was increased in stage 3 and 4 NB. As2O3 significantly arrested SK-N-SH cells in the G2/M phase. In addition, TrkA, TrkB and TrkC expression levels were significantly upregulated by higher concentrations of As2O3 treatment, notably in the 48-h treatment period. Our findings suggested that to achieve the maximum effect and appropriate regulation of Trk expression in NB stages 1, 2 and 4S, As2O3 treatment should be at relatively higher concentrations for longer delivery times;however, for NB stages 3 and 4, an appropriate concentration and infusion time for As2O3 must be carefully determined.ConclusionThe present findings suggested that As2O3 induced Trk expression in SK-N-SH cells to varying degrees and may be a promising adjuvant to current treatments for NB due to its apoptotic effects.

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Section: Introductionmentioning

confidence: 99%

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Xiong

Liu

et al. 2018

Biol Res

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“…Recently, increasing evidence has shown that anti-oxidative signaling was activated in drug resistant cancer cells [30]. For example, the upregulation of antioxidant enzyme catalase resulted in a 10-fold resistance to H2O2 or tert-butyl hydroperoxide in HL-60/AR leukemia cells [31]. Antioxidant enzyme peroxiredoxin II overexpression inhibited cisplatin and H 2 O 2 -induced apoptosis in SNU638 cells [32].…”

Section: Discussionmentioning

confidence: 99%

p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells

Xia¹,

Yan²,

Zhou³

et al. 2020

J. Cancer

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Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H: quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer.

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“…Our CD20 Ab × mPEG scFv strategy provides an "adaptable" option (clinical mAb × mPEG) for leukemia-resistant treatment as the CD20-end of the BsAb can be replaced by any kind of anti-leukemia tumor marker Ab after CD20 resistance. Another type of drug resistance occurs when leukemia cells express drug resistant proteins, MDR1 and MRP1, which act as drug e ux pumps, which can mediate the doxorubicin resistance [37,38]. The anti-mPEG scFv of BsAbs can actively "grab" any kind of liposomal drug that is modi ed with PEG such as PEGylated polymeric micelles [39], Irinotecan [40] or other PEGylated liposomal drugs in clinical use [41].…”

Section: Discussionmentioning

confidence: 99%

Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab×mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity

Chen

Cheng

et al. 2020

Preprint

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Background Tumor-targeted nanoparticles hold great promise as new tools for therapy of liquid cancers. Furthermore, the therapeutic efficacy of nanoparticles can be improved by enhancing the cancer cellular internalization. Methods In this study, we developed a humanized bispecific antibody (BsAbs: CD20 Ab×mPEG scFv) which retains the clinical anti-CD20 whole antibody (Ofatumumab) and is fused with anti-mPEG single chain antibodies (scFv) that can target the systemic liquid tumor cells. This combination achieves the therapeutic function and simultaneously “grabs” PEGylated liposomal doxorubicin (PLD) to enhance the cellular internalization and anticancer activity of PLD. Results We successfully constructed the CD20 Ab×mPEG scFv and proved that CD20 Ab×mPEG scFv can target CD20-expressing Raji cells and simultaneously grab PEGylated liposomal DiD increasing the internalization ability up to 60% in 24 h. We further showed that the combination of CD20 Ab×mPEG scFv and PLD successfully led to a 9-fold increase in tumor cytotoxicity (LC 50 : 0.38 nM) compared to the CD20 Ab×DNS scFv and PLD (lC 50 : 3.45 nM) in vitro . Importantly, a combination of CD20 Ab×mPEG scFv and PLD had greater anti-liquid tumor efficacy ( P = 0.0005) in Raji-bearing mice than CD20 Ab×DNS scFv and PLD. Conclusion Our results indicate that this “double-attack” strategy using CD20 Ab×mPEG scFv and PLD can retain the tumor targeting ( first attack ) and confer PLD tumor-selectivity ( second attack ) to enhance PLD internalization and improve therapeutic efficacy in liquid tumors.

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Characteristics of doxorubicin-selected multidrug-resistant human leukemia HL‑60 cells with tolerance to arsenic trioxide and contribution of leukemia stem cells

Cited by 16 publications

References 31 publications

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

Arsenic trioxide induces cell cycle arrest and affects Trk receptor expression in human neuroblastoma SK-N-SH cells

p62 Suppressed VK3-induced Oxidative Damage Through Keap1/Nrf2 Pathway In Human Ovarian Cancer Cells

Double attack strategy for leukemia using a pre-targeting bispecific antibody (CD20 Ab×mPEG scFv) and actively attracting PEGylated liposomal doxorubicin to enhance anti-tumor activity

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