Histological changes of cervical tumours following Zanthoxylum acanthopodium DC treatment, and its impact on cytokine expression

Saudi J Biol Sci. 2022 Apr;29(4):2706-2718. doi: 10.1016/j.sjbs.2021.12.065. Epub 2022 Jan 4.

Abstract

Cervical cancer is the second most lethal cancer in Indonesia, behind breast cancer. One of the reasons cancer cells are difficult to treat is that the immune system is sometimes unable to recognise them as foreign. Cytokinin therapy is carried out so that the immune system can strengthen its response to cancer cells, with the aim of slowing or stopping the development of malignant cells. Zanthoxylum acanthopodium DC, also known as andaliman, is an Indonesian herb and a member of the Rutaceae family. It is rich in antioxidants and has anti-inflammatory and anti-cancer properties. The current study aimed to investigate the histological changes and changes in the expression of cytokines, such as IL-10, IL1β, VEGFR1, and TGFβ1, associated with andaliman treatment. Sample tissues and serums extracted from cervical cancer rat models were used. Rats were divided into five groups: a control group (C-), cancer model group (C+), cancer with a dose of Z. acanthopodium methanolic extract (ZAM) 100 mg/body weight (BW) ZAM (ZAM100), cancer with a dose of ZAM 200 mg/BW ZAM (ZAM200), and cancer with a dose of ZAM 400 mg/BW ZAM (ZAM400). Treatment lasted for 1 month. Blood samples were prepared for ELISA analysis, and cervical tissue was stained for immunohistochemistry using antibodies against IL-10, IL-1β, VEGFR1, and TGFβ1. Administration of ZAM had no significant effect on rat body weight and cervical organs (p > 0.05). However, it impacted haematological parameters in rats with cervical cancer (p < 0.05). Elevated malondialdehyde levels may be linked to superoxide dismutase deficiency in tumour tissue. ZAM significantly decreased the expression of IL1β, TGFβ1, and VEGFR1 (p < 0.01), while it increased the expression of IL-10. Therefore, ZAM may be a potential target for molecular cytokine therapy for cervical cancer.

Keywords: C+, Cancer rats; Cervical cancer; Cytokines; C−, Control; DAB, 3,3-Diaminobenzidine; IARC, International Agency for Research on Cancer; IFN, Interferon; IL-10; IL-10, Interleukin-10; IL1β; IL1β, Interleukin 1-beta; MDA, Malondialdehyde; NGAL, Neutrophil gelatinase associated lipocalin; SGOT, Serum Glumatic Oxaloacetic Transamine; SGPT, Serum Glutamic Pyruvic Transaminase; SOD, Superoxide dismutase; TGFβ1; TGFβ1, Transforming growth factor-beta; VEGF, Vascular endothelial growth factor; VEGFR1; VEGFR1, Vascular endothelial growth factor receptor-1; ZAM100, Cancer rats + 100mg/Kg BW of ZAM; ZAM200, Cancer rats + 200mg/Kg BW of ZAM; ZAM400, Cancer rats + 400mg/Kg BW of ZAM; Zanthoxylum.