The effect of kefir polysaccharide extract on the expression of matrix metalloproteinase 9 (MMP-9) and integrin activation of HeLa cervical carcinoma culture cell

Yahya Irwanto; Eddy Mustofa; Teguh Wiyono; Dodi Tri Oktafianto; Arif Rahman Nurdianto; Robby Rinaldi Widodo

doi:10.15562/bmj.v11i2.3650

The effect of kefir polysaccharide extract on the expression of matrix metalloproteinase 9 (MMP-9) and integrin activation of HeLa cervical carcinoma culture cell

Yahya Irwanto ,

Eddy Mustofa ,

Teguh Wiyono ,

Dodi Tri Oktafianto ,

Arif Rahman Nurdianto ,

Robby Rinaldi Widodo ,

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DOI: https://doi.org/10.15562/bmj.v11i2.3650 |
Published: 2022-08-13

Abstract

Background: Cervical cancer is the leading cause of cancer in the world, especially in developing countries. Kefir is a goat's milk product that contains a lot of nutrients and bioactive complex which are involved in the synthesis of the anticancer, and have anticarcinogenic and antimutagenic effect. Integrins are involved in various biological processes associated with cancer development, such as migration, invasion, differentiation and proliferation. MMP-9 can also degrade ECM through proteolytic action, affecting cell-cell interactions in ECM. This research aimed to see the effect of kefir on MMP-9 and integrins activation. Thus, it is expected that kefir can be used as an additional supplement in patients with cervical cancer.

Methods: This research study was conducted in an experimental laboratory in vitro using HeLa cells as the object of research. Data were analyzed using the SPSS program to determine the most effective dose of kefir and a regression test to determine the effect between integrins and MMP-9.

Results: The mean value of MMP-9 and integrin at a dose of 180 µg/ml was 165.1 ± 5.8 and 378.5 ± 12.6 respectively. This result had a significant value of p = 0.0000 for both MMP-9 and integrin-b. In the regression test, the value of p = 0.05 was obtained while the coefficient value was positive (0.565).

Conclusion: The higher the expression of MMP-9, the activation of the integrin-b would increase. Kefir extract dosage of 180 µg/ml significantly reduced MMP-9 and Integrin-b expression. MMP-9 affects improving Integrin-b

References

Arbyn M, Weiderpass E, Bruni L, de Sanjosé S, Saraiya M, Ferlay J, et al. Estimates of incidence and mortality of cervical cancer in 2018: a worldwide analysis. Lancet Glob Heal. 2020 Feb;8(2):e191–203.
Campbell ID, Humphries MJ. Integrin structure, activation, and interactions. Cold Spring Harb Perspect Biol. 2011 Mar;3(3).
Huang H. Matrix Metalloproteinase-9 (MMP-9) as a Cancer Biomarker and MMP-9 Biosensors: Recent Advances. Sensors (Basel). 2018 Sep;18(10).
Pittayapruek P, Meephansan J, Prapapan O, Komine M, Ohtsuki M. Role of Matrix Metalloproteinases in Photoaging and Photocarcinogenesis. Int J Mol Sci. 2016 Jun;17(6).
Liu Z, Li C, Huang M, Tong C, Zhang X, Wang L, et al. Positive regulatory effects of perioperative probiotic treatment on postoperative liver complications after colorectal liver metastases surgery: a double-center and double-blind randomized clinical trial. BMC Gastroenterol. 2015 Mar;15:34.
Wang N, Zhu M, Tsao SW, Man K, Zhang Z, Feng Y. Up-Regulation of TIMP-1 by Genipin Inhibits MMP-2 Activities and Suppresses the Metastatic Potential of Human Hepatocellular Carcinoma. PLoS One. 2012;7(9).
Khoury N, El-Hayek S, Tarras O, El-Sabban M, El-Sibai M, Rizk S. Kefir exhibits anti‑proliferative and pro‑apoptotic effects on colon adenocarcinoma cells with no significant effects on cell migration and invasion. Int J Oncol. 2014 Nov;45(5):2117–27.
Kudo Y, Iizuka S, Yoshida M, Nguyen PT, Siriwardena SBSM, Tsunematsu T, et al. Periostin directly and indirectly promotes tumor lymphangiogenesis of head and neck cancer. PLoS One. 2012;7(8):e44488.
Batra J, Robinson J, Mehner C, Hockla A, Miller E, Radisky DC, et al. PEGylation extends circulation half-life while preserving in vitro and in vivo activity of tissue inhibitor of metalloproteinases-1 (TIMP-1). PLoS One. 2012;7(11):e50028.
Gruber G, Hess J, Stiefel C, Aebersold DM, Zimmer Y, Greiner RH, et al. Correlation between the tumoral expression of beta3-integrin and outcome in cervical cancer patients who had undergone radiotherapy. Br J Cancer. 2005 Jan;92(1):41–6.
Zhan P, Liu L, Liu B, Mao X-G. Expression of integrin β1 and its significance in squamous cell carcinoma of the cervix. Mol Med Rep. 2014 Jun;9(6):2473–8.
Cagnet S, Faraldo MM, Kreft M, Sonnenberg A, Raymond K, Glukhova MA. Signaling events mediated by α3β1 integrin are essential for mammary tumorigenesis. Oncogene. 2014 Aug;33(34):4286–95.
Huveneers S, Danen EHJ. Adhesion signaling - crosstalk between integrins, Src and Rho. J Cell Sci. 2009 Apr;122(Pt 8):1059–69.
Segawa S, Fujiya M, Konishi H, Ueno N, Kobayashi N, Shigyo T, et al. Probiotic-derived polyphosphate enhances the epithelial barrier function and maintains intestinal homeostasis through integrin-p38 MAPK pathway. PLoS One. 2011;6(8):e23278.
Dia VP, Gonzalez de Mejia E. Lunasin potentiates the effect of oxaliplatin preventing outgrowth of colon cancer metastasis, binds to α5β1 integrin and suppresses FAK/ERK/NF-κB signaling. Cancer Lett. 2011 Dec;313(2):167–80.
Morini M, Mottolese M, Ferrari N, Ghiorzo F, Buglioni S, Mortarini R, et al. The α3β1 integrin is associated with mammary carcinoma cell metastasis, invasion, and gelatinase B (MMP-9) activity. Int J Cancer. 2000;87(3):336–42.
DiPersio CM, Hodivala-Dilke KM, Jaenisch R, Kreidberg JA, Hynes RO. alpha3beta1 Integrin is required for normal development of the epidermal basement membrane. J Cell Biol. 1997 May;137(3):729–42.
Kreidberg JA, Symons JM. Integrins in kidney development, function, and disease. Am J Physiol Renal Physiol. 2000 Aug;279(2):F233-42.
Chattopadhyay N, Wang Z, Ashman LK, Brady-Kalnay SM, Kreidberg JA. alpha3beta1 integrin-CD151, a component of the cadherin-catenin complex, regulates PTPmu expression and cell-cell adhesion. J Cell Biol. 2003 Dec;163(6):1351–62.