Synergistic induction of apoptosis in liver cancer cells: exploring the combined potential of doxorubicin and XL-888

Kaplan, Özlem

doi:10.1007/s12032-023-02181-9

Cited by 2 publications

(3 citation statements)

References 36 publications

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“…XL-888 led to a reduction in HSP27 protein abundance, an elevation in Hsp70 expression, and did not induce a significant alteration in HSP90 protein levels. Similarly, in our previous study, XL-888 significantly increased HSP70 levels in the liver cancer cell lines HUH-7 and HepG2 [ 5 ]. The phenomenon is attributable to the separation of the heat shock factor-1 (HSF1) monomer from HSP90, which is followed by HSF1 trimerization, nuclear translocation, and HSP70 transcription activation.…”

Section: Resultssupporting

confidence: 70%

“…However, it is difficult to conclude that Debio0932 induces the apoptotic pathway in SH-SY5Y cells. Numerous studies have indicated that HSP90 inhibitors reduce cell proliferation by causing apoptosis in cancer cells [ 5 , 6 ]. Kim et al revealed that the HSP90 inhibitor geldanamycin reduced cell viability in the SH-SY5Y human neuroblastoma cell line and induced the apoptotic pathway via caspase activation, mitochondrial release of cytochrome c, and subsequent PARP cleavage [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

“…Due to the presence of many HSP90 client proteins, HSP90 inhibition targets multiple signaling pathways simultaneously and may exert multimodal therapeutic effect. Many chemically diverse HSP90 inhibitors have been shown in various studies to exhibit anticancer activity [ 5 – 8 ]. XL-888 is an oral next-generation HSP90 inhibitor that significantly limits HSP90 activity without inhibiting other kinases [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

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Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Kaplan,

Gökşen Tosun

2024

Med Oncol

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Neuroblastoma is a common nervous system tumor in childhood, and current treatments are not adequate. HSP90 is a molecular chaperone protein that plays a critical role in the regulation of cancer-related proteins. HSP90 inhibition may exert anticancer effects by targeting cancer-related processes such as tumor growth, cell proliferation, metastasis, and apoptosis. Therefore, HSP90 inhibition is a promising strategy in the treatment of various types of cancer, and the development of next-generation inhibitors could potentially lead to more effective and safer treatments. XL-888 and Debio0932 is a next-generation HSP90 inhibitor and can inhibit the correct folding and stabilization of client proteins that cancer-associated HSP90 helps to fold correctly. In this study, we aimed to investigate the comprehensive molecular pathways of the anticancer activity of XL-888 and Debio0932 in human neuroblastoma cells SH-SY5Y. The cytotoxic effects of XL-888 and Debio0932 on the neuroblastoma cell line SH-SY5Y cells were evaluated by MTT assay. Then, the effect of these HSP90 inhibitors on the expression of important genes in cancer was revealed by Quantitative Real Time Polymerase Chain Reaction (qRT-PCR) method. The qRT-PCR data were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) biological process tools. Finally, the effect of HSP90 inhibitors on HSP27, HSP70 and HSP90 protein expression was investigated by Western blotting analysis. The results revealed that XL-888 and Debio0932 had a role in regulating many cancer-related pathways such as migration, invasion, metastasis, angiogenesis, and apoptosis in SH-SY5Y cells. In conclusion, it shows that HSP90 inhibitors can be considered as a promising candidate in the treatment of neuroblastoma and resistance to chemotherapy.

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Section: Resultssupporting

confidence: 70%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Kaplan,

Gökşen Tosun

2024

Med Oncol

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Antagonistic interaction of HSP90 inhibitor XL-888 and 5-FU combination treatment in breast cancer cells

Gökşen Tosun

2024

Int. Adv. Res. Eng. J.

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Breast cancer is a serious global health problem, and investigation of innovative therapeutic approaches in its treatment is important to increase survival. Combination therapy targets more than one mechanism simultaneously and has recently emerged as an effective treatment strategy by using different therapeutic agents together. The purpose of this study was to determine the combined effects of the conventional chemotherapeutic agent 5-Fluorouracil (5-FU) and the HSP90 inhibitor XL-888 on breast cancer cell lines. MDA-MB-231 and MCF-7 cells were subjected to varying concentrations of XL-888 and 5-FU as individual treatments and in combination. The MTT test was employed to determine cell viability, and the Chou-Talalay technique was utilized to compute combination indices. Contrary to expectations, the HSP90 inhibitor XL-888 and 5-FU coadministration showed antagonistic effects in MDA-MB-231 and MCF-7 breast cancer cells. The results highlight the importance of careful consideration when combining these agents in breast cancer treatment regimens because their co-administration may not produce the expected synergistic results. The implications of the present research are anticipated to contribute to the developing of enhanced and focused treatment modalities for various cancers, with a particular emphasis on breast cancer.

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Synergistic induction of apoptosis in liver cancer cells: exploring the combined potential of doxorubicin and XL-888

Cited by 2 publications

References 36 publications

Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Molecular pathway of anticancer effect of next-generation HSP90 inhibitors XL-888 and Debio0932 in neuroblastoma cell line

Antagonistic interaction of HSP90 inhibitor XL-888 and 5-FU combination treatment in breast cancer cells

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