Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells

Levesley, Jane; Steele, Lynette P.; Brüning-Richardson, Anke; Davison, Adam; Zhou, Jia; Ding, Chunyong; Lawler, Sean E.; Short, Susan

doi:10.1093/neuonc/nox134

Cited by 26 publications

(24 citation statements)

References 39 publications

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“…There was spontaneous green fluorescence of cells after transfection, so the gate detection by flow cytometry was regulated in cell apoptosis with negative staining and blank controls. The detailed procedure was carried out according to standard protocols described previously [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

LncRNA HOTTIP-Mediated HOXA11 Expression Promotes Cell Growth, Migration and Inhibits Cell Apoptosis in Breast Cancer

Sun

Zeng

Gan

et al. 2018

IJMS

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As the most common cause of cancer death in women, the pathogenesis of breast cancer still remains unclear. Here, we reported a long non-coding RNA (lncRNA), HOTTIP (HOXA transcript at the distal tip), that may play an important role in the pathogenesis of breast cancer. Using gain-and-loss-of experiments in vitro and in vivo, we observed the marked upregulation of HOTTIP/HOXA11 in the breast cancer cell line, MCF-7, and the downregulation of HOTTIP or HOXA11, which might inhibit cell proliferation and migration but promote cell apoptosis in breast cancer MCF-7 cells. In addition, by further rescue experiments with HOXA11 overexpression, we uncovered a novel potential regulatory mechanism between HOTTIP and one of its physical HOXA clusters, HOXA11. Hence, HOTTIP may mediate, at least partly, HOXA11 expression involved in cell growth, migration, and apoptosis of breast cancer MCF-7 cells.

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Section: Methodsmentioning

confidence: 99%

LncRNA HOTTIP-Mediated HOXA11 Expression Promotes Cell Growth, Migration and Inhibits Cell Apoptosis in Breast Cancer

Sun

Zeng

Gan

et al. 2018

IJMS

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“…However, some encouragement for evaluating this strategy can be derived from studies showing enhanced levels of apoptosis when cisplatin and inhibitors of antiapoptotic proteins are used in combination. For example, WEHI-539 (a BCL-XL-selective small molecule inhibitor) and ABT-263 potentiated apoptosis when combined with cisplatin (72 h concomitant treatment) in the DAOY medulloblastoma cell line [128]. ABT-263 also sensitized small cell lung cancer cells to cisplatin, an effect that was typically associated with enhanced apoptosis [129].…”

Section: Identification Of Drugs That Transition Dormant or Potentialmentioning

confidence: 99%

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Murray

Mirzayans

2020

IJMS

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Chemotherapy is intended to induce cancer cell death through apoptosis and other avenues. Unfortunately, as discussed in this article, moderate doses of genotoxic drugs such as cisplatin typical of those achieved in the clinic often invoke a cytostatic/dormancy rather than cytotoxic/apoptosis response in solid tumour-derived cell lines. This is commonly manifested by an extended apoptotic threshold, with extensive apoptosis only being seen after very high/supralethal doses of such agents. The dormancy response can be associated with senescence-like features, polyploidy and/or multinucleation, depending in part on the p53 status of the cells. In most solid tumour-derived cells, dormancy represents a long-term survival mechanism, ultimately contributing to disease recurrence. This review highlights the nonlinearity of key aspects of the molecular and cellular responses to bulky DNA lesions in human cells treated with chemotherapeutic drugs (e.g., cisplatin) or ultraviolet light-C (a widely used tool for unraveling details of the DNA damage-response) as a function of the level of genotoxic stress. Such data highlight the growing realization that targeting dormant cancer cells, which frequently emerge following conventional anticancer treatments, may represent a novel strategy to prevent or, at least, significantly suppress cancer recurrence.

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“…Central memory T cells have a better capacity to reconstitute the pool of memory T cells and to mediate protective immunity when compared with relatively short-lived effector memory T cells, which may have contributed to the beneficial increase in vitro survival during long-term culturing. Other Bcl-2 family proteins, such as Bcl-xl and MCL-1, have shown similar anti-apoptosis effects in other cell types [ 42 , 43 ]. It will be interesting to investigate whether Bcl-xl and MCL-1 could function similarly to Bcl-2 in CAR-T cells.…”

Section: Discussionmentioning

confidence: 99%

Bcl-2 Enhances Chimeric Antigen Receptor T Cell Persistence by Reducing Activation-Induced Apoptosis

Han

et al. 2021

Cancers

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Purpose: To evaluate the potential added value of integrating anti-apoptotic molecules for improving the anti-tumor activity of CAR-T cells. Methods: Four small molecules inhibiting apoptosis were tested for their ability to prevent activated induced CAR-T cell death. Five CD20-targeting, CD137 (4-1BB) and CD3ζ integrated CAR-T cells (20BBZ) with constitutively expressed anti-apoptotic genes were established, and we screened out the strongest proliferation enhancer: Bcl-2. The memory subtype and the exhaustion markers of CAR-T cells were analyzed. The anti-tumor activities of Bcl-2 integrating CAR-T cells (20BBZ-Bcl-2) were evaluated in vitro and in a mouse xenograft lymphoma model. Conclusion: The 20BBZ-Bcl-2 CAR-T cells showed improved proliferation ability compared to 20BBZ CAR-T cells in vitro. In addition, activation-induced apoptosis was reduced in the 20BBZ-Bcl-2 CAR-T cells. Consistent with the enhanced proliferation in vitro, 20BBZ-Bcl-2 CAR-T cells exhibited improved anti-tumor activity in a mouse xenograft lymphoma model.

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Selective BCL-XL inhibition promotes apoptosis in combination with MLN8237 in medulloblastoma and pediatric glioblastoma cells

Cited by 26 publications

References 39 publications

LncRNA HOTTIP-Mediated HOXA11 Expression Promotes Cell Growth, Migration and Inhibits Cell Apoptosis in Breast Cancer

LncRNA HOTTIP-Mediated HOXA11 Expression Promotes Cell Growth, Migration and Inhibits Cell Apoptosis in Breast Cancer

Cellular Responses to Platinum-Based Anticancer Drugs and UVC: Role of p53 and Implications for Cancer Therapy

Bcl-2 Enhances Chimeric Antigen Receptor T Cell Persistence by Reducing Activation-Induced Apoptosis

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