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Mylabris phalerata induces the apoptosis and cell cycle delay in HCC, and potentiates the effect of sorafenib based on the molecular and network pharmacology approach

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Abstract

Background

In patients with hepatocellular carcinoma (HCC), surgical treatment may be recommended at an early stage. Sorafenib is the only drug approved for the treatment of advanced HCC, but the survival period is only extended by 2–3 months. Also, sorafenib develops resistance.

Objective

It needs to find the new chemotherapy drugs for HCC. We investigated growth inhibition of cancer cell by Mylabris phalerata (MP) in the human Huh-7 HCC cell line.

Methods

Huh-7 cells were treated with MP examined by in vitro assay. And we checked whether MP could increase sensitivity to in vivo model. In addition, we employed the NGS analysis to provide transcriptomic insight.

Results

MP inhibits growth of HCC cell lines by inducing apoptosis and G2/M cell cycle arrest. MP enhanced AMPK activation and reduced mTOR, and increased cyclin B1 levels. MP also inhibited migration and synergistically enhanced sensitivity to sorafenib in the Huh-7 cells. In the RNA-seq analysis, the differentially expressed genes by MP were primarily associated with extracellular matrix, angiogenesis and migration.

Conclusions

Our results indicate that MP potentially have anti-cancer effects and might be applied for combination therapy with sorafenib for HCC.

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Acknowledgements

Authors would like to thank to the Ph.D. fellowship program of Kyungpook National University and Dongguk University for completing this work.

Funding

This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (number: HF20C0212) and (number: HF21C0061), and by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2022R1I1A3053818).

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Author notes

  1. Young Woo Kim and Seon Been Bak have equally contributed to this work.

Authors and Affiliations

  1. Kyungpook National University, Daegu, 41566, Korea

    Young Woo Kim, Su Youn Baek & Il Kon Kim

  2. School of Korean Medicine, Dongguk University, Gyeongju, 38066, Korea

    Young Woo Kim, Seon Been Bak, Won-Yung Lee & Un-Jung Yun

  3. Yeungnam University, Gyeongsan, 38541, Korea

    Su Youn Baek

  4. School of Korean Medicine, Gachon University, Seongnam, 13120, Korea

    Won-Yung Lee

  5. Department of Veterinary Physiology, College of Veterinary Medicine, Gyeongsang National University, Jinju, 52828, Republic of Korea

    Kwang-Il Park

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Contributions

PKI, KIK and KYW: conceptualization; KYW, BSY and YUJ: investigation—original submission; BSB and LWY: investigation—revised submission; KYW, BSY and YUJ: writing—original draft preparation; LWY, BSB, KIK and PKI: writing—review and editing; KYW, LWY and PKI: funding acquisition. All authors have read and agreed to the published version of the manuscript.

Corresponding authors

Correspondence to Won-Yung Lee, Un-Jung Yun or Kwang-Il Park.

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Conflict of interest

Young Woo Kim declares that he/she has no conflict of interest. Seon Been Bak declares that he/she has no conflict of interest. Su Youn Baek declares that he/she has no conflict of interest. Il-Kon Kim declares that he/she has no conflict of interest. Won-Yung Lee declares that he/she has no conflict of interest. Un-Jung Yun declares that he/she has no conflict of interest. Kwang-Il Park declares that he/she has no conflict of interest.

Ethical approval

All animal experimental procedures were approved by the Yeungnam University Institutional Animal Care and Use Committee and were conducted in accordance with the guidelines of the National Institutes of Health.

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Kim, Y.W., Bak, S.B., Baek, S.Y. et al. Mylabris phalerata induces the apoptosis and cell cycle delay in HCC, and potentiates the effect of sorafenib based on the molecular and network pharmacology approach. Mol. Cell. Toxicol. 19, 731–742 (2023). https://doi.org/10.1007/s13273-022-00300-7

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  • DOI: https://doi.org/10.1007/s13273-022-00300-7

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