Garlic Peel Extract As an Antioxidant Inhibits Triple-negative Breast Tumor Growth and Angiogenesis by Inhibiting Cyclooxygenase-2 Expression

Overview

Journal Food Sci Nutr

Specialty Biotechnology

Date 2024 Nov 18

PMID 39554336

Authors

Yushi Dong

Jiyue Zhang

Aijun Xie

Xiqing Yue

Mohan Li

Qian Zhou

Affiliations

Soon will be listed here.

Abstract

Garlic peels are frequently disposed of as agro-waste; their bioactivity and physiological activity for health benefits and disease protection are neglected. This study aims to examine the potential inhibitory effects of garlic peel extract as an antioxidant on 4 T1 triple-negative breast cancer (TNBC) tumors in mice. The bioactive constituents of garlic peel were identified through HPLC-MS/MS analysis, while the antioxidant properties of garlic peel extract were assessed using peroxyl radical scavenging capacity (PSC) and cellular antioxidant activity (CAA) assays. Subsequently, the inhibitory effects of garlic peel extract on 4T1 tumor growth were evaluated using a 4T1 model. The results showed that 433 polyphenol compounds were found in garlic peel extract; among them, flavonoids and phenolic acid are the primary polyphenols with natural antioxidant activity, and both high and low concentrations of the extract exhibited tumor-suppressive effects. Immunohistochemistry was employed to assess the expression levels of COX-2, CD31, VEGFA, MMP2, and MMP9 in tumor tissues in order to investigate the antioxidant properties of garlic peel extract, specifically its ability to suppress COX-2 expression. The findings of this study offer a foundation for the advancement of garlic peel-based functional products and contribute to the identification of potential anti-cancer agents and therapeutic targets.

References

von Rahden B, Stein H, Puhringer F, Koch I, Langer R, Piontek G . Coexpression of cyclooxygenases (COX-1, COX-2) and vascular endothelial growth factors (VEGF-A, VEGF-C) in esophageal adenocarcinoma. Cancer Res. 2005; 65(12):5038-44. DOI: 10.1158/0008-5472.CAN-04-1107. View

Hou Z, Falcone D, Subbaramaiah K, Dannenberg A . Macrophages induce COX-2 expression in breast cancer cells: role of IL-1β autoamplification. Carcinogenesis. 2011; 32(5):695-702. PMC: 3086701. DOI: 10.1093/carcin/bgr027. View

Ji M, Gong X, Li X, Wang C, Li M . Advanced Research on the Antioxidant Activity and Mechanism of Polyphenols from Species-A Review. Molecules. 2020; 25(4). PMC: 7071004. DOI: 10.3390/molecules25040917. View

Kellett M, Greenspan P, Pegg R . Modification of the cellular antioxidant activity (CAA) assay to study phenolic antioxidants in a Caco-2 cell line. Food Chem. 2017; 244:359-363. DOI: 10.1016/j.foodchem.2017.10.035. View

Howe L . Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer. Breast Cancer Res. 2007; 9(4):210. PMC: 2206709. DOI: 10.1186/bcr1678. View

Shang A, Cao S, Xu X, Gan R, Tang G, Corke H . Bioactive Compounds and Biological Functions of Garlic ( L.). Foods. 2019; 8(7). PMC: 6678835. DOI: 10.3390/foods8070246. View

Diehn M, Cho R, Lobo N, Kalisky T, Dorie M, Kulp A . Association of reactive oxygen species levels and radioresistance in cancer stem cells. Nature. 2009; 458(7239):780-3. PMC: 2778612. DOI: 10.1038/nature07733. View

Kim W, Seo S, Byun Y, Kang H, Kim Y, Lee S . The Anticancer Effects of Garlic Extracts on Bladder Cancer Compared to Cisplatin: A Common Mechanism of Action via Centromere Protein M. Am J Chin Med. 2018; 46(3):689-705. DOI: 10.1142/S0192415X18500362. View

Li M, Li Q, Dong H, Zhao S, Ning J, Bai X . Pilose antler polypeptides enhance chemotherapy effects in triple-negative breast cancer by activating the adaptive immune system. Int J Biol Macromol. 2022; 222(Pt B):2628-2638. DOI: 10.1016/j.ijbiomac.2022.10.045. View

10.

Timoshenko A, Chakraborty C, Wagner G, Lala P . COX-2-mediated stimulation of the lymphangiogenic factor VEGF-C in human breast cancer. Br J Cancer. 2006; 94(8):1154-63. PMC: 2361247. DOI: 10.1038/sj.bjc.6603067. View

11.

Shen X, Xie A, Li Z, Jiang C, Wu J, Li M . Research Progress for Probiotics Regulating Intestinal Flora to Improve Functional Dyspepsia: A Review. Foods. 2024; 13(1). PMC: 10778471. DOI: 10.3390/foods13010151. View

12.

Wolfe K, Liu R . Cellular antioxidant activity (CAA) assay for assessing antioxidants, foods, and dietary supplements. J Agric Food Chem. 2007; 55(22):8896-907. DOI: 10.1021/jf0715166. View

13.

Tsubura A, Lai Y, Kuwata M, Uehara N, Yoshizawa K . Anticancer effects of garlic and garlic-derived compounds for breast cancer control. Anticancer Agents Med Chem. 2011; 11(3):249-53. DOI: 10.2174/187152011795347441. View

14.

Hui C, Qi X, Qianyong Z, Xiaoli P, Jundong Z, Mantian M . Flavonoids, flavonoid subclasses and breast cancer risk: a meta-analysis of epidemiologic studies. PLoS One. 2013; 8(1):e54318. PMC: 3548848. DOI: 10.1371/journal.pone.0054318. View

15.

Saeed K, You L, Chen C, Zhao Z, Fu X, Liu R . Comparative assessment of phytochemical profiles and antioxidant and antiproliferative activities of kiwifruit (Actinidia deliciosa) cultivars. J Food Biochem. 2019; 43(11):e13025. DOI: 10.1111/jfbc.13025. View

16.

Li Q, Li M, Zheng K, Tang S, Ma S . Expression pattern analysis and drug differential sensitivity of cancer-associated fibroblasts in triple-negative breast cancer. Transl Oncol. 2020; 14(1):100891. PMC: 7563008. DOI: 10.1016/j.tranon.2020.100891. View

17.

Singh B, Berry J, Shoher A, Ayers G, Wei C, Lucci A . COX-2 involvement in breast cancer metastasis to bone. Oncogene. 2007; 26(26):3789-96. DOI: 10.1038/sj.onc.1210154. View

18.

Reis-Filho J, Tutt A . Triple negative tumours: a critical review. Histopathology. 2008; 52(1):108-18. DOI: 10.1111/j.1365-2559.2007.02889.x. View

19.

Adinew G, Taka E, Mendonca P, Messeha S, Soliman K . The Anticancer Effects of Flavonoids through miRNAs Modulations in Triple-Negative Breast Cancer. Nutrients. 2021; 13(4). PMC: 8067583. DOI: 10.3390/nu13041212. View

20.

Sivula A, Talvensaari-Mattila A, Lundin J, Joensuu H, Haglund C, Ristimaki A . Association of cyclooxygenase-2 and matrix metalloproteinase-2 expression in human breast cancer. Breast Cancer Res Treat. 2005; 89(3):215-20. DOI: 10.1007/s10549-004-0714-4. View