Characterization of Apoptosis in a Breast Cancer Cell Line After IL-10 Silencing

Overview

Journal Asian Pac J Cancer Prev

Specialty Oncology

Date 2018 Mar 28

PMID 29582634

Citations 19

Authors

Moureq R Alotaibi

Zeinab K Hassan

Salim S Al-Rejaie

Musaad A Alshammari

Mashal M Almutairi

Ali R Alhoshani

Wael A Alanazi

Mohamed M Hafez

Othman A Al-Shabanah

Affiliations

Soon will be listed here.

Abstract

Background: Breast cancer is affected by the immune system in that different cytokines play roles in its initiation and progression. Interleukin-10 (IL-10), an anti-inflammatory cytokine, is an immunosuppressive factor involved in tumorigenesis. The present study was conducted to investigate the gene silencing effect of a small interference RNA (siRNA) targeting IL-10 on the apoptotic pathway in breast cancer cell line. Methods: The siRNA targeting IL-10 and a glyceraldehyde 3-phosphate dehydrogenase (GAPDH) clone were introduced into MDA-MB-231 cells. Real-time PCR assays were used to determine IL-10 and GAPDH gene expression levels, in addition to those for protein kinase B (AKT), phosphoinositide 3-kinase (PI3K), B-cell lymphoma 2 (Bcl2), caspase-3 and caspase-9 genes related to apoptosis. Results: Inhibition of IL-10 by the siRNA accelerated apoptosis and was accompanied by significant increase in caspase-3 and caspase-9 and a significant decrease in PI3K, AKT and Bcl2 expression levels compared to the non-transfected case. Conclusions: In conclusion, the production of IL-10 may represent a new escape mechanism by breast cancer cells to evade destruction by the immune system. IL-10 gene silencing causes down regulation of both PI3K/AKT and Bcl2 gene expression and also increases the Bbc3, BAX caspase3, and caspase 3 cleavage expression levels. IL–10 might represent a promising new target for therapeutic strategies.

Citing Articles

In Vitro Evaluation, Chemical Profiling, and In Silico ADMET Prediction of the Pharmacological Activities of Root Extract.

Alsaleh A, Aziz I, Aljowaie R, Alshalan R, Alkubaisi N, Aboul-Soud M Pharmaceuticals (Basel). 2025; 17(12.

PMID: 39770489 PMC: 11728498. DOI: 10.3390/ph17121646.

Evaluation of the anticancer and antibacterial activities of moscatilin.

Aljeldah M Heliyon. 2024; 10(10):e31131.

PMID: 38818150 PMC: 11137398. DOI: 10.1016/j.heliyon.2024.e31131.

MEIS2 suppresses breast cancer development by downregulating IL10.

Xiao Y, Liu Y, Sun Y, Huang C, Zhong S Cancer Rep (Hoboken). 2024; 7(5):e2064.

PMID: 38711262 PMC: 11074520. DOI: 10.1002/cnr2.2064.

Chemical Composition, Antioxidant, Anticancer, and Antibacterial Activities of Roots and Seeds of L. Methanol Extract.

Aziz I, Alshalan R, Rizwana H, Alkhelaiwi F, Almuqrin A, Aljowaie R Pharmaceuticals (Basel). 2024; 17(1).

PMID: 38256954 PMC: 10819509. DOI: 10.3390/ph17010121.

Pharmacogenomic and epigenomic approaches to untangle the enigma of IL-10 blockade in oncology.

Elemam N, Mekky R, Rashid G, Braoudaki M, Youness R Expert Rev Mol Med. 2024; 26:e1.

PMID: 38186186 PMC: 10941350. DOI: 10.1017/erm.2023.26.

References

Rychly B, Sidlova H, Danis D . [The 2007 World Health Organisation classification of tumours of the central nervous system, comparison with 2000 classification]. Cesk Patol. 2008; 44(2):35-6. View

Bachis A, Colangelo A, Vicini S, Doe P, De Bernardi M, Brooker G . Interleukin-10 prevents glutamate-mediated cerebellar granule cell death by blocking caspase-3-like activity. J Neurosci. 2001; 21(9):3104-12. PMC: 6762554. View

Puthier D, Derenne S, Barille S, Moreau P, Harousseau J, Bataille R . Mcl-1 and Bcl-xL are co-regulated by IL-6 in human myeloma cells. Br J Haematol. 1999; 107(2):392-5. DOI: 10.1046/j.1365-2141.1999.01705.x. View

Alas S, Emmanouilides C, Bonavida B . Inhibition of interleukin 10 by rituximab results in down-regulation of bcl-2 and sensitization of B-cell non-Hodgkin's lymphoma to apoptosis. Clin Cancer Res. 2001; 7(3):709-23. View

Fiorentino D, Bond M, Mosmann T . Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989; 170(6):2081-95. PMC: 2189521. DOI: 10.1084/jem.170.6.2081. View

Carpi A, Nicolini A, Antonelli A, Ferrari P, Rossi G . Cytokines in the management of high risk or advanced breast cancer: an update and expectation. Curr Cancer Drug Targets. 2009; 9(8):888-903. DOI: 10.2174/156800909790192392. View

Chen Q, Daniel V, Maher D, Hersey P . Production of IL-10 by melanoma cells: examination of its role in immunosuppression mediated by melanoma. Int J Cancer. 1994; 56(5):755-60. DOI: 10.1002/ijc.2910560524. View

Shiozaki E, Chai J, Shi Y . Oligomerization and activation of caspase-9, induced by Apaf-1 CARD. Proc Natl Acad Sci U S A. 2002; 99(7):4197-202. PMC: 123625. DOI: 10.1073/pnas.072544399. View

Heckel M, Wolfson A, Slachta C, Schwarting R, Salgame P, Katsetos C . Human breast tumor cells express IL-10 and IL-12p40 transcripts and proteins, but do not produce IL-12p70. Cell Immunol. 2010; 266(2):143-53. DOI: 10.1016/j.cellimm.2010.09.010. View

10.

Reddy R, Chen G, Newstead M, Moore T, Zeng X, Tateda K . Alveolar macrophage deactivation in murine septic peritonitis: role of interleukin 10. Infect Immun. 2001; 69(3):1394-401. PMC: 98033. DOI: 10.1128/IAI.69.3.1394-1401.2001. View

11.

Lin X, Bohle A, Dohrmann P, Leuschner I, Schulz A, Kremer B . Overexpression of phosphatidylinositol 3-kinase in human lung cancer. Langenbecks Arch Surg. 2001; 386(4):293-301. DOI: 10.1007/s004230100203. View

12.

Nakano K, Vousden K . PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell. 2001; 7(3):683-94. DOI: 10.1016/s1097-2765(01)00214-3. View

13.

Qian J, Zou Y, Rahman J, Lu B, Massion P . Synergy between phosphatidylinositol 3-kinase/Akt pathway and Bcl-xL in the control of apoptosis in adenocarcinoma cells of the lung. Mol Cancer Ther. 2009; 8(1):101-9. PMC: 3110728. DOI: 10.1158/1535-7163.MCT-08-0973. View

14.

Hafez M, Al-Shabanah O, Al-Harbi N, Al-Harbi M, Al-Rejaie S, Alsurayea S . Association between paraoxonases gene expression and oxidative stress in hepatotoxicity induced by CCl4. Oxid Med Cell Longev. 2014; 2014:893212. PMC: 4248367. DOI: 10.1155/2014/893212. View

15.

McIlwain D, Berger T, Mak T . Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2015; 7(4). PMC: 4382736. DOI: 10.1101/cshperspect.a026716. View

16.

Reed J . Bcl-2 family proteins: regulators of chemoresistance in cancer. Toxicol Lett. 1995; 82-83:155-8. DOI: 10.1016/0378-4274(95)03551-6. View

17.

Hikisz P, Kilianska Z . PUMA, a critical mediator of cell death--one decade on from its discovery. Cell Mol Biol Lett. 2012; 17(4):646-69. PMC: 6275950. DOI: 10.2478/s11658-012-0032-5. View

18.

Szanto A, Bognar Z, Szigeti A, Szabo A, Farkas L, Gallyas Jr F . Critical role of bad phosphorylation by Akt in cytostatic resistance of human bladder cancer cells. Anticancer Res. 2009; 29(1):159-64. View

19.

Simon N, Antignani A, Sarnovsky R, Hewitt S, Fitzgerald D . Targeting a Cancer-Specific Epitope of the Epidermal Growth Factor Receptor in Triple-Negative Breast Cancer. J Natl Cancer Inst. 2016; 108(8). PMC: 5017938. DOI: 10.1093/jnci/djw028. View

20.

Belle J, Petrov J, Langlais D, Robert F, Cencic R, Shen S . Repression of p53-target gene Bbc3/PUMA by MYSM1 is essential for the survival of hematopoietic multipotent progenitors and contributes to stem cell maintenance. Cell Death Differ. 2016; 23(5):759-75. PMC: 4832099. DOI: 10.1038/cdd.2015.140. View