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. 2025 Nov-Dec;39(6):3195-3204.
doi: 10.21873/invivo.14119.

Licoricidin Enhances Paclitaxel-induced Apoptosis Through Endoplasmic Reticulum Stress in Human Cervical Cancer Cells

Ching-Ting Tai #  1   2 , Yi-Chang Chen #  3   4 , Yi-Hsien Hsieh  1 , Chia-Liang Lin  5   6 , Tsung-Ho Ying  7   8 , Jin-Cherng Chen  9   10
Affiliations

Licoricidin Enhances Paclitaxel-induced Apoptosis Through Endoplasmic Reticulum Stress in Human Cervical Cancer Cells

Ching-Ting Tai et al. In Vivo. 2025 Nov-Dec.

Abstract

Background/aim: The adverse side effects associated with chemotherapeutic agents have prompted the exploration of natural compounds as adjuvants to chemotherapy, offering more effective therapeutic alternatives. Licoricidin, a bioactive constituent of licorice, possesses diverse pharmacological properties. However, the antitumor mechanisms underlying the therapeutic effects of Licoricidin combined with paclitaxel in cervical cancer remain unclear and further investigations are warranted.

Materials and methods: Cell growth and apoptosis were assessed using the MTT assay and Annexin V/PI staining. Endoplasmic reticulum (ER) stress was evaluated using the ER-ID assay. The expression of apoptosis- and ER stress-related proteins in response to the combined treatment was analyzed using western blotting.

Results: Combined treatment with licoricidin and paclitaxel effectively inhibited cell growth and induced apoptosis in human HeLa and C-33A cells. We further revealed that this combined treatment increased the expression of apoptotic proteins (c-PARP, Bax, and DR5) while decreasing the expression of pro-caspase proteins (pro-caspase-3 and pro-caspase-9) in HeLa cells. In addition, the combined treatment induced ER stress, as evidenced by decreased expression levels of ERp44, ERp57, and ERp72, whereas the expression of GRP78 was increased in HeLa cells.

Conclusion: The combination of licoricidin and paclitaxel induced ER stress-mediated apoptosis and may serve as a potential antitumor therapeutic strategy against human cervical cancer cells.

Keywords: Licoricidin; apoptosis; cervical cancer cells; endoplasmic reticulum; paclitaxel.

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Conflict of interest statement

The Authors declare no conflicts of interest to report regarding the present study.

Figures

Figure 1
Figure 1
Chemical structures of licoricidin and paclitaxel.
Figure 2
Figure 2
Combination treatment with licoricidin and paclitaxel inhibits growth of human cervical cancer cells. (A) HeLa, (B) C-33A, and (C) SiHa cells were treated with licoricidin (20 μM), paclitaxel (10 μM), or their combination for 24 h. Cell growth was assessed using the MTT assay. Data are presented as the mean±SD of three independent experiments. **p<0.01 compared with untreated cells; #p <0.05 compared with licoricidin or paclitaxel treatment.
Figure 3
Figure 3
Combination treatment with licoricidin and paclitaxel induces apoptosis in HeLa and C-33A cells. Cells were treated with licoricidin (20 μM), paclitaxel (10 μM), or their combination for 24 h. Apoptosis was analyzed using Annexin V/PI staining and flow cytometry. Data are presented as the mean±SD of three independent experiments. **p<0.01 compared with untreated cells; ##p<0.01 compared with licoricidin or paclitaxel treatment.
Figure 4
Figure 4
Effect of combination treatment with licoricidin and paclitaxel on intrinsic and extrinsic apoptotic proteins in HeLa cells. Cells were treated with licoricidin (20 μM), paclitaxel (10 μM), or their combination for 24 h. The expression of apoptosis-related proteins was analyzed using western blotting. β-actin was used as a loading control. Data are presented the mean±SD of three independent experiments. *p<0.05, **p<0.01 compared with untreated cells; #p<0.05 compared with licoricidin or paclitaxel treatment.
Figure 5
Figure 5
Combination treatment with licoricidin and paclitaxel induces ER stress in HeLa cells. Cells were treated with licoricidin (20 μM), paclitaxel (10 μM), or their combination for 24 h. ER stress was detected using ER-Tracker Green staining. Data are presented as the mean±SD of three independent experiments. **p<0.01 compared with untreated cells; #p<0.05 compared with licoricidin or paclitaxel treatment.
Figure 6
Figure 6
Effect of combination treatment with licoricidin and paclitaxel on ER stress–related proteins in HeLa cells. Cells were treated with licoricidin (20 μM), paclitaxel (10 μM), or their combination for 24 h. The expression of ER stress–related proteins (ERp44, ERp57, ERp72, and GRP78) was analyzed using western blotting. β-actin was used as a loading control. Data are presented as the mean±SD of three independent experiments. *p<0.05, **p<0.01 compared with untreated cells; #p<0.05 compared with licoricidin or paclitaxel treatment.
Figure 7
Figure 7
Proposed mechanism of ER stress and apoptosis induction by combination treatment with licoricidin and paclitaxel in human cervical cancer cells.
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References

    1. Wu S, Jiao J, Yue X, Wang Y. Cervical cancer incidence, mortality, and burden in China: a time-trend analysis and comparison with England and India based on the global burden of disease study 2019. Front Public Health. 2024;12:1358433. doi: 10.3389/fpubh.2024.1358433. - DOI - PMC - PubMed
    1. Massobrio R, Bianco L, Campigotto B, Attianese D, Maisto E, Pascotto M, Ruo Redda MG, Ferrero A. New frontiers in locally advanced cervical cancer treatment. J Clin Med. 2024;13(15):4458. doi: 10.3390/jcm13154458. - DOI - PMC - PubMed
    1. Yao G, Qiu J, Zhu F, Wang X. Survival of patients with cervical cancer treated with definitive radiotherapy or concurrent chemoradiotherapy according to histological subtype: a systematic review and meta-analysis. Front Med (Lausanne) 2022;9:843262. doi: 10.3389/fmed.2022.843262. - DOI - PMC - PubMed
    1. Yadagiri U, Shaik R, Kolure R, Fatima T, Khan H. Immuno-therapeutics in clinical trials for cervical cancer. Cancer Biother Radiopharm. 2025;40(6):377–388. doi: 10.1089/cbr.2025.0031. - DOI - PubMed
    1. Zhang Z, Liu M, An Y, Gao C, Wang T, Zhang Z, Zhang G, Li S, Li W, Li M, Wang G. Targeting immune microenvironment in cervical cancer: current research and advances. J Transl Med. 2025;23(1):888. doi: 10.1186/s12967-025-06896-3. - DOI - PMC - PubMed

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