Identification of RAD54 homolog B as a promising therapeutic target for breast cancer

Feng, Jing; Hu, Juanjuan; Xia, Ying

doi:10.3892/ol.2019.10854

Cited by 4 publications

(3 citation statements)

References 49 publications

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“…However, its importance in anticancer therapy needs further investigations. In fact, alterations of RAD54B have been detected in several cancers, including lung adenocarcinoma, breast cancer, and hepatoma ( 44 , 45 , 46 , 47 ). RAD54B silencing often leads to reduced cell proliferation and enhanced apoptosis ( 44 , 47 ).…”

Section: Resultsmentioning

confidence: 99%

RAD54B mutations enhance the sensitivity of ovarian cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors

Liu

Lin

Liu

et al. 2022

Journal of Biological Chemistry

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Section: Resultsmentioning

confidence: 99%

RAD54B mutations enhance the sensitivity of ovarian cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors

Liu

Lin

Liu

et al. 2022

Journal of Biological Chemistry

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“…JaponiconeA (JA) is a natural product isolated from Inula japonica Thunb 16 . A previous study showed that JA inhibited breast cancer cell proliferation by inhibiting the expression of RAD54B 17 . Moreover, JA inhibited the growth of non-small cell lung cancer cells via mitochondrial-mediated pathways 18 .…”

Section: Introductionmentioning

confidence: 98%

JaponiconeA induces apoptosis of bortezomib-sensitive and -resistant myeloma cells in vitro and in vivo by targeting IKKβ

Liu

et al. 2021

Cancer Biol Med

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Objective: Multiple myeloma (MM) remains incurable with high rates of relapse. New therapeutic drugs are therefore urgently needed to improve the prognosis. JaponiconeA (JA), a natural product isolated from Inula japonica Thunb, has shown good anti-MM potential. A comprehensive study should therefore be conducted to identify both the in vitro and in vivo mechanisms of the anti-MM effects of JA. Methods: CCK8 assays and flow cytometry were used to detect the proliferation, apoptosis, and cell cycle of MM cell lines when treated with JA. In vivo experiments were conducted using subcutaneous xenograft mouse models. We also identified possible targets and the mechanism of JA using RNA-seq and c-Map databases, and identified the specific targets of JA in bortezomib-sensitive and -resistant MM cell lines using CETSA, DARTS, and rescue experiments. Furthermore, JA and bortezomib were used separately or together to characterize their possible synergistic effects. Results: In vitro, JA inhibited proliferation, and induced apoptosis and G2/M phase arrest in MM cell lines, and selectively killed primary CD138 + MM cells. In vivo, JA also demonstrated a strong anti-tumor effect with no observable toxicity. In addition, JA showed synergetic effects in combination with bortezomib, and enhanced the anti-tumor effect of bortezomib in bortezomibresistant cells. CETSA and DARTS confirmed direct binding of JA to NF-κB inhibitor kinase beta (IKKβ), and overexpression of IKKβ or knockdown of IκBα partially rescued the apoptosis induced by JA. Conclusions: JA exhibited strong anti-tumor effects in MM. It sensitized myeloma cells to bortezomib and overcame NF-κB-induced drug resistance by inhibiting IKKβ, providing a new treatment strategy for MM patients.

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“…JaponiconeA (JA) is a natural product isolated from Inula japonica Thunb (16). Previous study has demonstrated that JA inhibited breast cancer cell proliferation by inhibiting the expression of RAD54B (17).And JA could inhibit the growth of non-small cell lung cancer cells via mitochondria-mediated pathways (18). In addition, JA was also effective in Burkitt lymphoma (19)Here, we found that JA showed potent anti-tumor effect in MM both in vitro and in vivo but spared the normal cells.…”

Section: Introductionmentioning

confidence: 99%

JaponiconeA Induces Apoptosis of Bortezomib-Sensitive and –Resistant Myeloma Cells In Vitro and In Vivo through Targeting IKKβ

Liu

et al. 2020

Preprint

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Backgrounds: Multiple myeloma (MM) is a clonal proliferative disease of abnormal plasma cells. Relapse and drug resistance still remain to be solved, so new therapeutic drugs are needed to be adopted to further improve the prognosis of MM. JaponiconeA (JA) is a natural product isolated from Inula japonica Thunb, the anti-tumor effect and mechanism in MM has not been studied.Methods: CCK8 and flow cytometry were used to detect the proliferation, apoptosis and cell cycle of MM cell lines with JA treatment. And the in vivo effects of JA were verified in the subcutaneous xenograft mice model of MM. In addition, we analyzed the possible targets and mechanism of JA through RNA-seq and c-Map databases, and we verified the specific target of JA in MM cell lines and bortezomib-resistant MM cell line through CETSA and rescue experiments. JA and bortezomib were used separately or together to treat MM cell lines to explore the synergetic effect. Results: In vitro experiments, JA inhibited proliferation, induced apoptosis and G2/M phase arrest of MM cell lines, and JA selectively killed primary CD138+ MM cells but spared normal human mononuclear cells. In vivo experiments, JA also showed good anti-tumor effect with no observable toxicity. In addition, JA achieved good synergetic effect in combination with bortezomib, and enhanced the anti-tumor effect of bortezomib in bortezomib-resistant cells. According to RNA-seq and c-Map data, the target protein of JA might be IKKβ. CETSA experiment confirmed that JA can bind IKKβ directly in vitro, and overexpression of IKKβ could partly rescue the apoptosis induced by JA.Conclusion: JA exhibited strong anti-tumor effects in MM. It sensitized myeloma cells to bortezomib and overcame NF-κB induced drug resistance through inhibiting IKKβ, which providing a new treatment strategy for MM patients.

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Identification of RAD54 homolog B as a promising therapeutic target for breast cancer

Cited by 4 publications

References 49 publications

RAD54B mutations enhance the sensitivity of ovarian cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors

RAD54B mutations enhance the sensitivity of ovarian cancer cells to poly(ADP-ribose) polymerase (PARP) inhibitors

JaponiconeA induces apoptosis of bortezomib-sensitive and -resistant myeloma cells in vitro and in vivo by targeting IKKβ

JaponiconeA Induces Apoptosis of Bortezomib-Sensitive and –Resistant Myeloma Cells In Vitro and In Vivo through Targeting IKKβ

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