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Zinc Oxide Nanoparticles Trigger Autophagy in the Human Multiple Myeloma Cell Line RPMI8226: an In Vitro Study

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Abstract

Multiple myeloma (MM) is a malignant clonal proliferative plasma cell tumor. Zinc oxide nanoparticles (ZnO NPs) are used for antibacterial and antitumor applications in the biomedical field. This study investigated the autophagy-induced effects of ZnO NPs on the MM cell line RPMI8226 and the underlying mechanism. After RPMI8226 cells were exposed to various concentrations of ZnO NPs, the cell survival rate, morphological changes, lactate dehydrogenase (LDH) levels, cell cycle arrest, and autophagic vacuoles were monitored. Moreover, we investigated the expression of Beclin 1 (Becn1), autophagy-related gene 5 (Atg5), and Atg12 at the mRNA and protein levels, as well as the level of light chain 3 (LC3). The results showed that ZnO NPs could effectively inhibit the proliferation and promote the death of RPMI8226 cells in vitro in a dose- and time-dependent manner. ZnO NPs increased LDH levels, enhanced monodansylcadaverine (MDC) fluorescence intensity, and induced cell cycle arrest at the G2/M phases in RPMI8226 cells. Moreover, ZnO NPs significantly increased the expression of Becn1, Atg5, and Atg12 at the mRNA and protein levels and stimulated the production of LC3. We further validated the results using the autophagy inhibitor 3-methyladenine (3‑MA). Overall, we observed that ZnO NPs can trigger autophagy signaling in RPMI8226 cells, which may be a potential therapeutic approach for MM.

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Data Availability

The data sets used and analyzed during the current study are available from the corresponding author on reasonable request.

Abbreviations

MM:

Multiple myeloma

ZnO NPs:

Zinc oxide nanoparticles

LDH:

Lactate dehydrogenase

Becn1:

Beclin 1

Atg5:

Autophagy-related gene 5

LC3:

Light chain 3

MDC:

Monodansylcadaverine

3-MA:

3-Methyladenine

PC:

Plasma cells

BM:

Bone marrow

TEM:

Transmission electron microscope

XRD:

X-ray diffraction

ANOVA:

Analysis of variance

PBMCs:

Peripheral blood mononuclear cells

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Funding

This study was funded by the National Natural Science Foundation of China (81974547) and the Natural Science Foundation of Shandong Province (ZR2019PH018, ZR2020KH023).

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Author notes

  1. Zonghong Li and Xuewei Yin contributed equally to this work and share first authorship

Authors and Affiliations

  1. Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China

    Zonghong Li, Xuewei Yin & Chunyi Lyu

  2. Department of Hematology, the Affiliated Hospital of Shandong University of Traditional Chinese Medicine, No. 16369#, Jingshi Road, Jinan, 250014, Shandong Province, China

    Jingyi Wang, Kui Liu, Siyuan Cui, Shumin Ding, Yingying Wang, Jinxin Wang & Ruirong Xu

  3. Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Shandong Academy of Eye Disease Prevention and Therapy, Affiliated Eye Hospital of Shandong, University of Traditional Chinese Medicine, No. 48#, Yingxiongshan Road, Jinan, Shandong Province, China

    Dadong Guo

  4. Key Laboratory of Integrated Traditional Chinese and Western Medicine for Hematology, Health Commission of Shandong Province, Jinan, 250014, China

    Ruirong Xu

  5. Institute of Hematology, Shandong University of Traditional Chinese Medicine, Jinan, 250014, China

    Ruirong Xu

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  1. Zonghong Li
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Contributions

Zonghong Li: conceptualization, data curation, formal analysis, investigation, methodology, writing—original draft. Xuewei Yin: conceptualization, data curation, formal analysis, investigation, methodology, writing—original draft. Chunyi Lyu: software, supervision, validation. Jingyi Wang: data curation, investigation, methodology. Kui Liu: investigation, methodology, validation. Siyuan Cui: investigation, methodology, validation. Shumin Ding: investigation, validation. Yingying Wang: investigation, visualization. Jinxin Wang: investigation, visualization. Dadong Guo: conceptualization, resources, supervision, writing—review and editing. Ruirong Xu: conceptualization, funding acquisition, project administration, writing—review & editing. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Dadong Guo or Ruirong Xu.

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Highlights

1. ZnO NPs effectively inhibited the proliferation of human MM RPMI8226 cells in vitro.

2. ZnO NPs enhanced Becn1, Atg5, Atg12, and LC3 expression in human MM RPMI8226 cells.

3. ZnO NPs trigger the autophagy signaling pathway in human MM RPMI8226 cells.

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Li, Z., Yin, X., Lyu, C. et al. Zinc Oxide Nanoparticles Trigger Autophagy in the Human Multiple Myeloma Cell Line RPMI8226: an In Vitro Study. Biol Trace Elem Res 202, 913–926 (2024). https://doi.org/10.1007/s12011-023-03737-6

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  • DOI: https://doi.org/10.1007/s12011-023-03737-6

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