Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis

Liu, Zhengrui; Wang, Jia; Xie, Siman; Zhang, Benteng; Yuan, Yan; Fu, Huaizi; Hao, Hongyun; Sun, Li; Yuan, Shengtao; Ding, Jian; Yu, Hong; Yang, Mei

doi:10.7150/jca.93621

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J Cancer 2024; 15(8):2318-2328. doi:10.7150/jca.93621 This issue Cite

Research Paper

Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis

Zhengrui Liu^1,2#, Jia Wang^1,2#, Siman Xie^1,2, Benteng Zhang^1,2, Yan Yuan^1,2, Huaizi Fu^1,2, Hongyun Hao^1,2, Li Sun^1,2, Shengtao Yuan^1,2, Jian Ding^3✉, Hong Yu^4✉, Mei Yang^1,2✉

1. Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing, China.
2. National key laboratory for multi-target natural drugs, China Pharmaceutical University, Nanjing, China.
3. Chinese Academy of Sciences Shanghai Institute of Materia Medica, Shanghai, China.
4. Department of Pathology, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, Jiangsu, China.
# These authors contributed equally.

Citation:

Liu Z, Wang J, Xie S, Zhang B, Yuan Y, Fu H, Hao H, Sun L, Yuan S, Ding J, Yu H, Yang M. Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis. J Cancer 2024; 15(8):2318-2328. doi:10.7150/jca.93621. https://www.jcancer.org/v15p2318.htm

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Abstract

Aim of the study: To investigate the anti-tumor effects of Lasiokaurin on breast cancer and explore its underlying molecular mechanism.

Materials and methods: In this study, MTT assay, plate colony formation assays, soft agar assay, and EdU assay were employed to evaluate the anti-proliferation effects of LAS. Apoptosis and cell cycle distribution were detected by flow cytometry. The molecular mechanism was predicted by performing RNA sequencing and verified by using immunoblotting assays. Breast cancer organiods derived from patient-derived xenografts model and MDA-MB-231 xenograft mouse model were established to assess the effect of LAS.

Results: Our study showed that LAS treatment significantly suppressed cell viability of 5 breast cancer cell lines, with the IC₅₀ value of approximately 1-5 μM. LAS also inhibitied the clonogenic ability and DNA synthesis of breast cancer cells, Moreover, LAS induced apoptosis and G2/M cell cycle arrest in SK-BR-3 and MDA-MB-231 cells. Notably, transcriptomic analysis predicted the mechanistic involvement of PLK1 in LAS-suppressed breast cancer progression. Our experiment data further verified that LAS reduced PLK1 mRNA and protein expression in breast cancer, accompanied by downregulating CDC25C and AKT phosphorylation. Ultimately, we confirmed that LAS inhibit breast cancer growth via inhibiting PLK1 pathway in vivo.

Conclusions: Collectively, our findings revealed that LAS inhibits breast cancer progression via regulating PLK1 pathway, which provids scientific evidence for the use of traditional Chinese medicine in cancer therapy.

Keywords: Lasiokaurin, breast cancer, G2/M phase block, apoptosis, PLK1

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APA

Liu, Z., Wang, J., Xie, S., Zhang, B., Yuan, Y., Fu, H., Hao, H., Sun, L., Yuan, S., Ding, J., Yu, H., Yang, M. (2024). Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis. Journal of Cancer, 15(8), 2318-2328. https://doi.org/10.7150/jca.93621.

ACS

Liu, Z.; Wang, J.; Xie, S.; Zhang, B.; Yuan, Y.; Fu, H.; Hao, H.; Sun, L.; Yuan, S.; Ding, J.; Yu, H.; Yang, M. Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis. J. Cancer 2024, 15 (8), 2318-2328. DOI: 10.7150/jca.93621.

NLM

CSE

Liu Z, Wang J, Xie S, Zhang B, Yuan Y, Fu H, Hao H, Sun L, Yuan S, Ding J, Yu H, Yang M. 2024. Lasiokaurin Regulates PLK1 to Induce Breast Cancer Cell G2/M Phase Block and Apoptosis. J Cancer. 15(8):2318-2328.

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