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RESEARCH PAPER
The mechanism of Scleromitrion diffusum (Willd.) R. J. Wang ethanol extract combined with carboplatin in treating cervical cancer
1
Department of Gynaecology, Fujian Provincial People’s Hospital, Fujian, China
2
Fujian University of Traditional Chinese Medicine, Fujian, China
Corresponding author
KEYWORDS
TOPICS
ABSTRACT
Introduction and objective:
Cervical cancer (CC) is a common cancer in women worldwide, imposing a substantial burden on healthcare systems. The aim of the study is to evaluate the effects of Scleromitrion diffusum (Willd.) R.J.Wang (SD) in combination with carboplatin (CBP) on CC cells, and to elucidate the underlying molecular mechanisms
Material and methods:
The half-maximal inhibitory concentration (IC₅₀) of SD and CBP in HeLa and CaSki cells was determined using the cell counting kit-8 (CCK-8) assay. Cell migration and invasion were assessed by Transwell assays. Levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and intracellular reactive oxygen species (ROS) were measured using enzyme-linked immunosorbent assay (ELISA). The expression of arachidonate 5-lipoxygenase (ALOX5) was analyzed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, the effects of combined SD and CBP treatment, as well as ALOX5 knockdown, on the malignant behaviour of cancer cells were investigated.
Results:
The results obtained demonstrated that SD effectively inhibited the proliferation, migration, and invasion of HeLa and CaSki cells. The combination of SD and CBP exhibited a synergistic effect, leading to further suppression of these malignant phenotypes. Mechanistically, the combined treatment elevated the levels of IL-6, TNF-α, and ROS, and downregulated ALOX5 expression. Notably, knockdown of ALOX5 expression was shown to suppress the malignant behaviours of both HeLa and CaSki cells.
Conclusions:
The combined application of SD and CBP markedly suppressed malignant phenotypes in HeLa and CaSki cells.
Cervical cancer (CC) is a common cancer in women worldwide, imposing a substantial burden on healthcare systems. The aim of the study is to evaluate the effects of Scleromitrion diffusum (Willd.) R.J.Wang (SD) in combination with carboplatin (CBP) on CC cells, and to elucidate the underlying molecular mechanisms
Material and methods:
The half-maximal inhibitory concentration (IC₅₀) of SD and CBP in HeLa and CaSki cells was determined using the cell counting kit-8 (CCK-8) assay. Cell migration and invasion were assessed by Transwell assays. Levels of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-α), and intracellular reactive oxygen species (ROS) were measured using enzyme-linked immunosorbent assay (ELISA). The expression of arachidonate 5-lipoxygenase (ALOX5) was analyzed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR). In addition, the effects of combined SD and CBP treatment, as well as ALOX5 knockdown, on the malignant behaviour of cancer cells were investigated.
Results:
The results obtained demonstrated that SD effectively inhibited the proliferation, migration, and invasion of HeLa and CaSki cells. The combination of SD and CBP exhibited a synergistic effect, leading to further suppression of these malignant phenotypes. Mechanistically, the combined treatment elevated the levels of IL-6, TNF-α, and ROS, and downregulated ALOX5 expression. Notably, knockdown of ALOX5 expression was shown to suppress the malignant behaviours of both HeLa and CaSki cells.
Conclusions:
The combined application of SD and CBP markedly suppressed malignant phenotypes in HeLa and CaSki cells.
PEER REVIEW INFORMATION
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REFERENCES (37)
1.
He ZY, Li HY, Yan J, et al. A prospective trial to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with arsenic trioxide and carboplatin in locally advanced cervical cancer: a study protocol for randomized controlled clinical. Trials. 2022;23(1):556. https://doi.org/10.1186/s13063....
2.
Wang Z, Liu M, Li GX, et al. A herbal pair of Scutellaria barbata D. Don and Scleromitrion diffusum (Willd.) R.J. Wang induced ferroptosis in ovarian cancer A2780 cells via inducing heme catabolism and ferritinophagy. J Integr Med. 2024;22(6):665–82. https://doi.org/10.1016/j.joim....
3.
Yang PW, Chen TT, Zhao WX, et al. Scutellaria barbata D. Don and Oldenlandia diffusa (Willd.) Roxb crude extracts inhibit hepatitis-B-virus-associated hepatocellular carcinoma growth through regulating circRNA expression. J Ethnopharmacol. 2021;275:114110. https://doi.org/10.1016/j.jep.....
4.
Kedhari Sundaram M, Raina R, Afroze N, et al. Quercetin modulates signaling pathways and induces apoptosis in cervical cancer cells. Biosci Rep. 2019;39(8). https://doi.org/10.1042/BSR201....
5.
He C, Lu X, Li J, et al. The effect of quercetin on cervical cancer cells as determined by inducing tumor endoplasmic reticulum stress and apoptosis and its mechanism of action. Am J Transl Res. 2021;13(5):5240–7.
6.
Chen X, Xu P, Zhang H, et al. EGFR and ERK activation resists flavonoid quercetin-induced anticancer activities in human cervical cancer cells in vitro. Oncol Lett. 2021;22(5):754. https://doi.org/10.3892/ol.202....
7.
Ji H, Li K, Xu W, et al. Prediction of the Mechanisms by Which Quercetin Enhances Cisplatin Action in Cervical Cancer: A Networ Pharmacology Study and Experimental Validation. Front Oncol. 2021;11:780387. https://doi.org/10.3389/fonc.2....
8.
Choi EY, Han EJ, Jeon SJ, et al. Kaempferol Inhibits Cervical Cancer Cells by Inducing Apoptosis and Autophagy via Inactivation of the PI3K/AKT/mTOR Signaling Pathway. Anticancer Res. 2024;44(7):2961–72. https://doi.org/10.21873/antic....
9.
Liu Q, Chen X, Tan Y, et al. Natural products as glycolytic inhibitors for cervical cancer treatment: A comprehensive review Biomed Pharmacother. 2024;175:116708. https://doi.org/10.1016/j.biop....
10.
Chen Y, Yu D, Zhu D, et al. Exploring alkaloids and flavonoids from natural sources: Emerging natural agents for inhibiting cervical cancer progression through apoptosis induction, anti-inflammatory effects, and oxidative stress reduction. Pathol Res Pract. 2025;272:156092. https://doi.org/10.1016/j.prp.....
11.
Tu LY, Bai HH, Cai JY, Deng SP. The mechanism of kaempferol induced apoptosis and inhibited proliferation in human cervical cancer SiHa cell: From macro to nano. Scanning. 2016;38(6):644–53. https://doi.org/10.1002/sca.21....
12.
Guan F, Du H, Li J, et al. Quercetin Alleviates LPS-Stimulated Myocardial Injury through Regulating ALOX5/PI3K/AKT Pathway in Sepsis. Cardiovasc Toxicol. 2024;24(10):1116–24. https://doi.org/10.1007/s12012....
13.
Yoshimoto T, Furukawa M, Yamamoto S, et al. Flavonoids: potent inhibitors of arachidonate 5-lipoxygenase. Biochem Biophys Res Commun. 1983;116(2):612–8. https://doi.org/10.1016/0006-2....
14.
Marin L, Gutierrez-Del-Rio I, Entrialgo-Cadierno R, et al. De novo biosynthesis of myricetin, kaempferol and quercetin in Streptomyces albus and Streptomyces coelicolor. PLoS One. 2018;13(11):e0207278. https://doi.org/10.1371/journa....
15.
Zargar S, Altwaijry N, Wani TA, Alkahtani HM. Evaluation of the Possible Pathways Involved in the Protective Effects of Quercetin, Naringenin, and Rutin at the Gene, Protein and miRNA Levels Using In-Silico Multidimensional Data Analysis. Molecules. 2023;28(13). https://doi.org/10.3390/molecu....
16.
Liu T, Xu X, Li J, et al. ALOX5 deficiency contributes to bladder cancer progression by mediating ferroptosis escape. Cell Death Dis. 2023;14(12):800. https://doi.org/10.1038/s41419....
17.
Zhao F, Hong J, Zhou G, et al. Elucidating the role of tumor-associated ALOX5+ mast cells with transformative function in cervical cancer progression via single-cell RNA sequencing. Front Immunol. 2024;15:1434450. https://doi.org/10.3389/fimmu.....
18.
Li L, Xiao Y, Xu Z, Wang S. Zileuton inhibits arachidonate-5- lipoxygenase to exert antitumor effects in preclinical cervical cance models. Cancer Chemother Pharmacol. 2021;88(6):953–60. https://doi.org/10.1007/s00280....
19.
Shan K, Feng N, Zhu D, et al. Free docosahexaenoic acid promotes ferroptotic cell death via lipoxygenase dependent and independent pathways in cancer cells. Eur J Nutr. 2022;61(8):4059–75. https://doi.org/10.1007/s00394....
20.
Ye W, Zhao Q, Li P, Zhou T. Scleromitrion diffusum (Willd.) R. J. Wang Inhibits Gastric Cancer via ERBB2/ERBB3/PI3K/AKT Pathway. Turk J Gastroenterol. 2024;35(11):831–8. https://doi.org/10.5152/tjg.20...
21.
Banerjee V, Sharda N, Huse J, et al. Synergistic potential of dual andrographolide and melatonin targeting of metastatic colon cancer cells: Using the Chou-Talalay combination index method. Eur J Pharmacol. 2021;897:173919. https://doi.org/10.1016/j.ejph....
22.
Saha S, Sultana S, Rahmat R, et al. Patterns of Different Cervical Cytokine Expression in High-Risk Human Papillomavirus-Infected Patients With Cervical Cancer and Its Precancerous Lesions. Clin Med Insights Oncol. 2025;19:11795549251316767. https://doi.org/10.1177/117955....
23.
Li Q, Kaidong L, Tian Z, et al. Association of Inflammatory Factors with Cervical Cancer: A Bidirectional Mendelian Randomization. J Inflamm Res. 2024;17:10119–30. https://doi.org/10.2147/JIR.S4....
24.
Tomaziu-Todosia Anton E, Anton GI, Scripcariu IS, et al. Oxidative Stress, Inflammation, and Antioxidant Strategies in Cervical Cancer-A Narrative Review. Int J Mol Sci. 2025;26(10). https://doi.org/10.3390/ijms26....
25.
Wang L, Wang B. ALOX5 regulates vascular smooth muscle cells pyroptosis to affect abdominal aortic aneurysm formation. Sci Rep. 2025;15(1):29123. https://doi.org/10.1038/s41598....
26.
Zhou J, Guo Z, Peng X, et al. Chrysotoxine regulates ferroptosis and the PI3K/AKT/mTOR pathway to prevent cervical cancer. J. Ethnopharmacol. 2025;338(Pt 3):119126. https://doi.org/10.1016/j.jep.....
27.
Feng J, Jin Y, Peng J, et al. Hedyotis diffusa willd extract suppresses colorectal cancer growth through multiple cellular pathways. Oncol Lett. 2017;14(6):8197–205. https://doi.org/10.3892/ol.201....
28.
Song Y, Wang H, Pan Y, Liu T. Investigating the Multi-Target Pharmaco-logical Mechanism of Hedyotis diffusa Willd Acting on Prostate Cancer: A Network Pharmacology Approach. Biomolecules. 2019;9(10). https://doi.org/10.3390/biom91....
29.
Yeh YC, Chen HY, Yang SH, et al. Hedyotis diffusa Combined with Scutellaria barbata Are the Core Treatment of Chinese Herbal Medicine Used for Breast Cancer Patients: A Population-Based Study. Evid Based Complement Alternat Med. 2014;2014:202378. https://doi.org/10.1155/2014/2....
30.
Huang L, Xu H, Wu T, Li G. Hedyotis diffusa Willd. Suppresses Hepatocellular Carcinoma via Downregulating AKT/mTOR Pathways. Evid Based Complement Alternat Med. 2021;2021:5210152. https://doi.org/10.1155/2021/5....
31.
Yang L, Wang Y, Shi S, et al. The TNF-alpha-induced expression of miR-130b protects cervical cancer cells from the cytotoxicity of TNF-alpha. FEBS Open Bio. 2018;8(4):614–27. https://doi.org/10.1002/2211-5....
32.
Valenzuela Cardenas M, Nowicki TS. TNF-alpha: Roles in pathogenesis and therapeutics in cancer. J Biol Chem. 2026;302(3):111251. https://doi.org/10.1016/j.jbc.....
33.
Sano E, Kazaana A, Tadakuma H, et al. Interleukin-6 sensitizes TNF-alpha and TRAIL/Apo2L dependent cell death through upregulation of death receptors in human cancer cells. Biochim Biophys Acta Mol Cell Res. 2021;1868(7):119037. https://doi.org/10.1016/j.bbam....
34.
Suzuki K, Nagao S, Shibutani T, et al. Phase II trial of paclitaxel, carboplatin, and bevacizumab for advanced or recurrent cervical cancer. Gynecol Oncol. 2019;154(3):554–7. https://doi.org/10.1016/j.ygyn....
35.
Huang W, Wen F, Yang P, et al. Yi-qi-hua-yu-jie-du decoction induces ferroptosis in cisplatin-resistant gastric cancer via the AKT/GSK3beta/NRF2/GPX4 axis. Phytomedicine. 2024;123:155220. https://doi.org/10.1016/j.phym....
36.
Hu WM, Liu SQ, Zhu KF, et al. The ALOX5 inhibitor Zileuton regulates tumor-associated macrophage M2 polarization by JAK/STAT and inhibits pancreatic cancer invasion and metastasis. Int Immunopharmacol. 2023;121:110505. https://doi.org/10.1016/j.inti....
37.
Amoah AS, Pestov NB, Korneenko TV, et al. Lipoxygenases at the Intersection of Infection and Carcinogenesis. Int J Mol Sci. 2024;25(7). https://doi.org/10.3390/ijms25....
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