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Alantolactone exhibits antiproliferative and apoptosis-promoting properties in colon cancer model via activation of the MAPK-JNK/c-Jun signaling pathway

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Abstract

Colorectal cancer (CRC) is one of the most common human malignancies in the digestive tract with high mortality. Alantolactone (ATL), as a plant-derived sesquiterpene lactone, has shown a variety of pharmacological activities, such as antibacterial, anti-inflammatory, anti-virus and so on. However, the exact molecular mechanism of ATL in colorectal cancer remains largely unknown. Here, we performed a study to explore the effect and mechanism of ATL on colorectal cancer. The CCK-8 assay, colony formation assay, Wound-healing and Transwell assays were performed to evaluate the cytotoxic effect, antiproliferative effect, anti-migratory and anti-invasive properties of ATL respectively. The xenograft tumor model was established in Balb/c mice to evaluate the anti-tumor effect. The expression levels of proteins involved the MAPK-JNK/c-Jun signaling pathway were measured by Western blot and RT-qPCR both in cells and tumor tissues. The results showed that ATL could inhibit the cells activities of various colon cancer cell lines. Moreover, ATL could induce HCT-116 cells nuclear pyknosis, mitochondrial membrane potential loss, G0/G1 phase arrest, as well as enhance the proportion of apoptosis cells and inhibit colony formation. The migration distance and invasion rate of cells were significantly reduced after treated with ATL. Additionally, in the xenograft model, ATL (50 mg/kg) significantly decreased the tumor tumor volume and weight (p < 0.001). For the anti-colon cancer mechanism, the ATL showed the anti-proliferative and pro-apoptosis effect by activating MAPK-JNK/c-Jun signaling pathway. In conclusion, ATL exhibits anti-proliferation and apoptosis-promoting potential in colon cancer via the activation of MAPK-JNK/c-Jun signaling pathway.

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Data Availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Not applicable.

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Funding

Financial support was provided by the National Natural Science Foundation of China (Grant Nos. 81920108033), Natural Science Foundation of Shanghai (Grant No. 20ZR1458000).

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Author notes

  1. Yijing Ren, Cheng Lv and Jing Zhang contributed equally to the work.

Authors and Affiliations

  1. The MOE key Laboratory of Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines, and the SATCM key Laboratory of New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine (SHUTCM), Shanghai, 201203, China

    Yijing Ren, Cheng Lv, Jing Zhang, Beibei Zhang, Bei Yue, Zhilun Yu, Hao Wang, Junyu Ren, Zhengtao Wang & Wei Dou

  2. Key Laboratory of Cell Engineering in Guizhou Province, The Affiliated Hospital of Zunyi Medical University, Zunyi City, 563003, Guizhou Province, China

    Xiaoping Luo

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  1. Yijing Ren
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Contributions

YR, CL, JZ performed experiments. BZ, BY, XL analyzed the data. ZY, HW drafted the manuscript. JR edited and revised manuscript. ZW, WD participated in research design and approved final version of manuscript. All authors reviewed the manuscript.

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Correspondence to Zhengtao Wang or Wei Dou.

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The authors declare that there is no conflict of interest regarding the publication of the manuscript.

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To work with mice samples, ethical approval (PZSHUTCM18122106) was obtained from the Animal Experimentation Ethics Committee at Shanghai University of Traditional Chinese Medicine.

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Ren, Y., Lv, C., Zhang, J. et al. Alantolactone exhibits antiproliferative and apoptosis-promoting properties in colon cancer model via activation of the MAPK-JNK/c-Jun signaling pathway. Mol Cell Biochem 476, 4387–4403 (2021). https://doi.org/10.1007/s11010-021-04247-6

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