Journal of Nutrition and Health

  • 제57권1호
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  • Pages.43-52
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  • 2024
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  • 2288-3886(pISSN)
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  • 2288-3959(eISSN)
한국영양학회 (The Korean Nutrition Society)
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MDA-MB-231 유방암 세포에서 석류 유래 나노베지클의 항암효과

The anti-cancer effect of pomegranate-derived nanovesicles on MDA-MB-231 breast cancer cells

  • 김동하 (경북대학교 의과학과 분자의학교실) ;
  • 김지수 (안동대학교 식품영양학과) ;
  • 권인숙 (안동대학교 식품영양학과) ;
  • 조영은 (안동대학교 식품영양학과)
  • Dong-ha Kim (Department of Molecular Medicine, Cell & Matrix Research Institute, Kyungpook National University) ;
  • Ji-Su Kim (Department of Food and Nutrition, Andong National University) ;
  • In-Sook Kwun (Department of Food and Nutrition, Andong National University) ;
  • Young-Eun Cho (Department of Food and Nutrition, Andong National University)
  • 투고 : 2023.11.21
  • 심사 : 2024.01.22
  • 발행 : 2024.02.28
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초록

본 연구에서는 석류 유래 나노베지클이 유방암 세포인 MDA-MB-231 세포에 항 혈관 신생효과와 세포 증식을 억제하는지 확인하고자 하였다. 석류 주스로부터 분리한 석류 유래 나노베지클(PNVs)이 평균 직경이 162 nm의 이중막 구조인 나노베지클을 검증하였다. MDA-MB-231 세포에 석류 유래 나노베지클의 내재화를 확인하였다. 석류 유래 나노베지클이 MDA-MB-231 세포에 농도 의존적으로 세포 증식률을 감소시키는 것을 확인하였다. 또한, 석류 유래 나노베지클이 MDA-MB-231 세포에 침윤 및 전이를 억제하는 것을 확인하였다. 마지막으로 세포 발현 단백질을 증가시키고 MMP-2, MMP-9 단백질의 발현을 감소시키는 것을 검증하였다. 본 연구는 석류 유래 나노베지클이 인간 유방암 세포인 MDA-MB-231 세포의 세포 침윤 및 전이를 억제하고 세포사멸을 시켜 항암효과가 있음을 제시하고 있다. 따라서 석류 유래 나노베지클이 유방암 예방 및 치료에 이용 가능함으로 시사된다.

Purpose: Cancer is the leading cause of death in Koreans, with breast cancer being the most common among women. Breast cancer readily metastasizes, and the existing treatment processes impose a significant burden on patients. This study examined whether pomegranate-derived exosome-like nanovesicles (PNVs) have anti-cancer effects by inhibiting cell infiltration and metastasis while increasing apoptosis on breast cancer MDA-MB-231 cells. Methods: Initially, exosome-like nanovesicles were isolated from pomegranate using ultracentrifugation. Subsequently, the size range of these nanovesicles was confirmed using nanoparticle tracking analysis. The ability of breast cancer MDA-MB-231 cells to internalize these natural nanovesicles was assessed with flourescence microscope. The anti-cancer effects of the PNVs were confirmed by applying various concentrations of PNVs (10, 50, 100 ㎍/mL) to MDA-MB-231 cells and systematically assessing their impact on cell viability and migration. Results: The round shape of the lipid bilayer in the PNVs was confirmed, providing crucial insights into their structural properties. We demonstrate that PNVs-associated DiD dye can be efficiently internalized by the MDA-MB-231 cells. The data showed that the PNVs inhibited cell viability, invasion rates, and migration in MDA-MB-231 cells. In addition, PNVs were absorbed into the MDA-MB-231 cells, leading to an increased expression of apoptosis proteins, such as cleaved caspase-3 and phosphorus-JNK, in a concentration-dependent manner. Furthermore, a reduction in cell infiltration and decreased expression of the transition markers MMP-2 and MMP-9 proteins were observed. Conclusion: For the first time, this study suggests that PNVs may be useful in the prevention or treatment of breast cancer by inhibiting the infiltration and metastasis of MDA-MB-231 cells and inducing apoptosis.

키워드

과제정보

This work was supported by National Research Foundation (NRF) of Korea grants funded by the Korean government (MSIT) (No. 2021R1C1C1008117).

참고문헌

  1. National Cancer Information Center. The incidence of breast cancer [Internet]. Goyang: National Cancer Information Center; 2024 [cited 2024 Feb 18]. Available from: https://www.cancer.go.kr/lay1/S1T639C640/contents.do.
  2. Jang HY, Lee SH, An IJ, Lee HN, Kim HR, Park YS, et al. Effects of delphinidin in anthocyanin on MDA-MB-231 breast cancer cells. J Korean Soc Food Sci Nutr 2014; 43(2): 231-237. https://doi.org/10.3746/jkfn.2014.43.2.231
  3. Choi SH, Hwang JH, Baek MC, Cho YE. Anti-cancer effect of glabridin by reduction of extracellular vesicles secretion in MDA-MB-231 human breast cancer cells. J Nutr Health 2022; 55(2): 240-249. https://doi.org/10.4163/jnh.2022.55.2.240
  4. Sim Y, Seo HJ, Kim DH, Lee SH, Kwon J, Kwun IS, et al. The effect of apple-derived nanovesicles on the osteoblastogenesis of osteoblastic MC3T3-E1 cells. J Med Food 2023; 26(1): 49-58. https://doi.org/10.1089/jmf.2022.K.0094
  5. Choi SH, Eom JY, Kim HJ, Seo W, Kwun HJ, Kim DK, et al. Aloe-derived nanovesicles attenuate inflammation and enhance tight junction proteins for acute colitis treatment. Biomater Sci 2023; 11(16): 5490-5501. https://doi.org/10.1039/D3BM00591G
  6. Hwang JH, Park YS, Kim HS, Kim DH, Lee SH, Lee CH, et al. Yam-derived exosome-like nanovesicles stimulate osteoblast formation and prevent osteoporosis in mice. J Control Release 2023; 355: 184-198. https://doi.org/10.1016/j.jconrel.2023.01.071
  7. Kim JS, Kim DH, Gil MC, Kwon HJ, Seo W, Kim DK, et al. Pomegranate-derived exosome-like nanovesicles alleviate binge alcohol-induced leaky gut and liver injury. J Med Food 2023; 26(10): 739-748. https://doi.org/10.1089/jmf.2023.K.0060
  8. Alfieri M, Leone A, Ambrosone A. Plant-derived nano and microvesicles for human health and therapeutic potential in nanomedicine. Pharmaceutics 2021; 13(4): 498.
  9. Suharta S, Barlian A, Hidajah AC, Notobroto HB, Ana ID, Indariani S, et al. Plant-derived exosome-like nanoparticles: a concise review on its extraction methods, content, bioactivities, and potential as functional food ingredient. J Food Sci 2021; 86(7): 2838-2850. https://doi.org/10.1111/1750-3841.15787
  10. Lee G, Park T, Lee DI, Park JR, Choi S. Detection of antifungal activities from pomegranate. J Korean Soc Food Sci Nutr 2015; 44(2): 287-290. https://doi.org/10.3746/jkfn.2015.44.2.287
  11. Jin SY. Study on activities of extracts from different parts of korean and iranian pomegranates. J Korean Soc Food Sci Nutr 2011; 40(8): 1063-1072.
  12. Zarfeshany A, Asgary S, Javanmard SH. Potent health effects of pomegranate. Adv Biomed Res 2014; 3(1): 100.
  13. Bagheri M, Fazli M, Saeednia S, Kor A, Ahmadiankia N. Pomegranate peel extract inhibits expression of β-catenin, epithelial mesenchymal transition, and metastasis in triple negative breast cancer cells. Cell Mol Biol 2018; 64(7): 86-91. https://doi.org/10.14715/cmb/2018.64.7.15
  14. Hou Z, Wang X, Yang Z, Deng Z, Zhang J, Zhong J, et al. Pomegranate-derived exosome-like nanovesicles ameliorate high-fat diet-induced nonalcoholic fatty liver disease via alleviating mitochondrial dysfunction. J Funct Foods 2023; 108: 105734.
  15. Cho YE, Song BJ. Pomegranate prevents binge alcohol-induced gut leakiness and hepatic inflammation by suppressing oxidative and nitrative stress. Redox Biol 2018; 18: 266-278. https://doi.org/10.1016/j.redox.2018.07.012
  16. Delgado NT, Rouver WD, Freitas-Lima LC, de Paula TD, Duarte A, Silva JF, et al. Pomegranate extract enhances endothelium-dependent coronary relaxation in isolated perfused hearts from spontaneously hypertensive ovariectomized rats. Front Pharmacol 2017; 7: 522.
  17. McFarlin BK, Strohacker KA, Kueht ML. Pomegranate seed oil consumption during a period of high-fat feeding reduces weight gain and reduces type 2 diabetes risk in CD-1 mice. Br J Nutr 2009; 102(1): 54-59. https://doi.org/10.1017/S0007114508159001
  18. Nunez-Sanchez MA, Gonzalez-Sarrias A, Garcia-Villalba R, Monedero-Saiz T, Garcia-Talavera NV, Gomez-Sanchez MB, et al. Gene expression changes in colon tissues from colorectal cancer patients following the intake of an ellagitannin-containing pomegranate extract: a randomized clinical trial. J Nutr Biochem 2017; 42: 126-133. https://doi.org/10.1016/j.jnutbio.2017.01.014
  19. Wang R, Ding Y, Liu R, Xiang L, Du L. Pomegranate: constituents, bioactivities and pharmacokinetics. Fruit Vegetable Cereal Sci Biotechnol 2010; 4(2): 77-87.
  20. Hengartner MO. The biochemistry of apoptosis. Nature 2000; 407(6805): 770-776. https://doi.org/10.1038/35037710
  21. Deveraux QL, Stennicke HR, Salvesen GS, Reed JC. Endogenous inhibitors of caspases. J Clin Immunol 1999; 19(6): 388-398. https://doi.org/10.1023/A:1020502800208
  22. Ashkenazi A. Targeting the extrinsic apoptosis pathway in cancer. Cytokine Growth Factor Rev 2008; 19(3-4): 325-331. https://doi.org/10.1016/j.cytogfr.2008.04.001
  23. Takahashi K, Loo G. Disruption of mitochondria during tocotrienol-induced apoptosis in MDA-MB-231 human breast cancer cells. Biochem Pharmacol 2004; 67(2): 315-324. https://doi.org/10.1016/j.bcp.2003.07.015
  24. Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol 2009; 27(31): 5287-5297. https://doi.org/10.1200/JCO.2009.23.5556
  25. Stetler-Stevenson WG. Type IV collagenases in tumor invasion and metastasis. Cancer Metastasis Rev 1990; 9(4): 289-303. https://doi.org/10.1007/BF00049520
  26. Anusha R, Ashin M, Priya S. Ginger exosome-like nanoparticles (GELNs) induced apoptosis, cell cycle arrest, and anti-metastatic effects in triple-negative breast cancer MDA-MB-231 cells. Food Chem Toxicol 2023; 182: 114102.