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Profile of Apoptotic Proteins After Curcumin Treatment by Antibody Array in H69AR Lung Cancer Cells

Year 2020, Volume: 79 Issue: 2, 157 - 162, 25.12.2020

Abstract

Objective: The aim of the study was to investigate the changes in the expression levels of apoptosis-related proteins after treatment with curcumin (Cur) on multiple drug-resistant H69AR non-small cell lung cancer cells. Materials and Methods: Viability of H69AR cells after Cur exposure (5-100 μg/mL) was evaluated via MTT assay at 24, 48 and 72 h. Apoptosis was assessed via ELISA assay. Apoptosis related proteins of breast cancer cell lines were analyzed by a Human Apoptosis Antibody Array. Protein-protein interactions were analyzed and visualized by using the STRING database. Results: Cur inhibited cell viability and induced apoptosis in H69AR cells. The IC50 value of Cur in H69AR cells was 8.75 μg/ mL. The array results showed that the protein levels of pro-apoptotic proteins such as Bad, Bax, Caspase-3, TRAIL R1, TRAIL R2, FADD, Fas, SMAC/DIABLO, HMOX2 were significantly increased by 2.4-, 3.1-, 2.6-, 3.1-, 3.4-, 2.4-, 2.1-, 4.1- and 5.5-fold in H69AR cells (p<0.05). Moreover, the protein levels of the anti-apoptotic proteins such as Bcl-2, cIAP-1, CLU and HIF1A were significantly decreased by 4.1-, 3.2-, 2.2- and 2.0-fold, respectively in H69AR cells by Cur exposure (p<0.05). Conclusion: Findings of this study suggested that Cur induced apoptosis of human H69AR cells via mediating several proteins involved in both extrinsic and intrinsic apoptotic pathways.

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References

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  • 28. Giam M, Huang DCS. Bouillet, P. BH3-only proteins and their roles in programmed cell death. Oncogene 2008; 27: 128-36.
  • 29. Zuo L, Zhou T, Pannell BK, Ziegler AC, Best TM. Biological and physiological role of reactive oxygen species–the good, the bad and the ugly. Acta Physiol 2015; 214: 329-48.
  • 30. Zhu Y, Bu S. Curcumin induces autophagy, apoptosis, and cell cycle arrest in human pancreatic cancer cells. Evid Based Complementary Altern Med 2017; 2017.
  • 31. Larasati YA, Yoneda-Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato JY. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci Rep 2018; 8: 1-13.
  • 32. Chen Q, Wang Y, Xu K, Lu G, Ying Z, Wu L, et al. Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Oncol Rep 2010; 23: 397-403.
  • 33. Kuttikrishnan S, Siveen KS, Prabhu KS, Khan AQ, Ahmed EI, Akhtar S, et al. Curcumin induces apoptotic cell death via inhibition of PI3-Kinase/AKT pathway in B- precursor acute lymphoblastic leukemia. Front Oncol 2019:9.
  • 34. Lu T, Zhu Z, Wu J, She H, Han R, Xu H, et al. DRAM1 regulates autophagy and cell proliferation via inhibition of the phosphoinositide 3-kinase-Akt-mTOR-ribosomal protein S6 pathway. Cell Commun Signal 2019; 17: 28.
  • 35. Johnson SM, Gulhati P, Arrieta I, Wang X, Uchida T, Gao T, et al. Curcumin inhibits proliferation of colorectal carcinoma by modulating Akt/mTOR signaling. Anticancer Res 2009; 29: 3185-3190.
  • 36. Shinojima N, Yokoyama T, Kondo Y, Kondo, S. Roles of the Akt/mTOR/p70S6K and ERK1/2 signaling pathways in curcumin-induced autophagy. Autophagy 2007; 3: 635-637.
  • 37. Moreau R, Kaur H. Curcumin and piperine inhibit mTORC1 signaling in intestinal epithelial cells. The FASEB Journal 2017; 31: 135-138.
  • 38. Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES. The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J Biol Chem 2002; 277: 21119-22.
Year 2020, Volume: 79 Issue: 2, 157 - 162, 25.12.2020

Abstract

References

  • 1. Molina JR, Adjei AA, Jett JR. Advances in chemotherapy of non-small cell lung cancer. Chest 2006; 130: 1211-19.
  • 2. Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker JrS, et al. American Society of Clinical Oncology treatment of unresectable non–small-cell lung cancer guideline: Update 2003. J Clin Oncol 2004; 22: 330-53.
  • 3. Sosa Iglesias V, Giuranno L, Dubois LJ, Theys J, Vooijs M. Drug resistance in non-small cell lung cancer: a potential for NOTCH targeting? Front Oncol 2018; 8: 267.
  • 4. Alibeiki F, Jafari N, Karimi M, Peeri Dogaheh H. Potent anti-cancer effects of less polar Curcumin analogues on gastric adenocarcinoma and esophageal squamous cell carcinoma cells. Sci Rep 2017; 7: 1-9.
  • 5. Aggarwal BB, Surh YJ, Shishodia S. The molecular targets and therapeutic uses of curcumin in health and disease. 1st edition. New York : Springer Science & Business Media; 2007.
  • 6. Priyadarsini KI. The chemistry of curcumin: From extraction to therapeutic agent. Molecules 2014; 19: 20091-12.
  • 7. Anand P, Sundaram C, Jhurani S, Kunnumakkara AB, Aggarwal BB. Curcumin and cancer: An “old-age” disease with an “age-old” solution. Cancer Lett 2008; 267: 133-64.
  • 8. Dorai T, Cao YC, Dorai B, Buttyan R, Katz AE. Therapeutic potential of curcumin in human prostate cancer. III. Curcumin inhibits proliferation, induces apoptosis, and inhibits angiogenesis of LNCaP prostate cancer cells in vivo. Prostate 2001; 47: 293-303.
  • 9. Mukhopadhyay A, Bueso-Ramos C, Chatterjee D, Pantazis P, Aggarwal BB. Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines. Oncogene 2001; 20: 7597–7609. 10. Liu Q, Loo WTY, Sze SCW, Tong Y. Curcumin inhibits cell proliferation of MDA-MB-231 and BT-483 breast cancer cells mediated by down-regulation of NFB, cyclinD and MMP-1 transcription. Phytomedicine 2009; 16: 916-22.
  • 11. Moragoda L, Jaszewski R, Majumdar AP. Curcumin induced modulation of cell cycle and apoptosis in gastric and colon cancer cells. Anticancer Res 2001; 21: 873-78.
  • 12. Atmaca H, Uzunoglu S. Anti-angiogenic effects of trabectedin (Yondelis; ET-743) on human breast cancer cells. Eur Cytokine Netw 2014; 25: 1-7.
  • 13. Karaca B, Kucukzeybek Y, Gorumlu G, Erten C, Gul MK, Cengiz E et al. Profiling of angiogenic cytokines produced by hormone-and drug-refractory prostate cancer cell lines, PC-3 and DU-145 before and after treatment with gossypol. Eur Cytokine Netw 2008; 19:176-84.
  • 14. Erten C, Karaca B, Kucukzeybek Y, Gorumlu G, Cengiz E, Gul MK, et al. Regulation of growth factors in hormone‐and drug‐resistant prostate cancer cells by synergistic combination of docetaxel and octreotide. BJU Int 2009; 104, 107-14.
  • 15. Von Mering C, Jensen LJ, Snel B, Hooper SD, Krupp M, Foglierini M, et al. STRING: known and predicted protein–protein associations, integrated and transferred across organisms. Nucleic Acids Res 2005; 33: 433-37.
  • 16. Scheff SW. Fundamental statistical principles for the neurobiologist: A survival guide. 1st edition. New York : Academic Press; 2016.
  • 17. Boroumand N, Samarghandian S, Hashemy SI. Immunomodulatory, anti-inflammatory, and antioxidant effects of curcumin. J Herbmed Pharmacol 2018; 7: 211-19.
  • 18. Jurenka JS. Anti-inflammatory properties of curcumin, a major constituent of Curcuma longa: a review of preclinical and clinical research. Altern Med Rev 2009; 14: 141-53.
  • 19. Hewlings SJ, Kalman DS. Curcumin: a review of its’ effects on human health. Foods 2017; 6: 92.
  • 20. Tomeh MA, Hadianamrei R, Zhao X. A review of curcumin and its derivatives as anticancer agents. Int J Mol Sci 2019; 20: 1033.
  • 21. Allegra A, Innao V, Russo S, Gerace D, Alonci A, Musolino C. Anticancer activity of curcumin and its analogues: preclinical and clinical studies. Cancer Invest 2017; 35: 1-22.
  • 22. Vallianou NG, Evangelopoulos A, Schizas N, Kazazis C. Potential anticancer properties and mechanisms of action of curcumin. Anticancer Res 2015; 35: 645-51.
  • 23. Mirski SE Gerlach JH, Cole SP. Multidrug resistance in a human small cell lung cancer cell line selected in adriamycin. Cancer Res 1987; 47: 2594-98.
  • 24. Li P, Qin H, Li X. The effect of curcumin on the apoptosis of lung cancer cells by regulating DJ-1-PTEN/PI3K/AKT signaling. Int J Clin Exp Med 2019; 12: 8739-45.
  • 25. Yang CL, Ma YG, Xue YX, Liu YY, Xie H, Qiu GR. Curcumin induces small cell lung cancer NCI-H446 cell apoptosis via the reactive oxygen species mediated mitochondrial pathway and not the cell death receptor pathway. DNA Cell Biol 2012; 31: 139-50.
  • 26. Jin H, Qiao F, Wang Y, Xu Y, Shang Y. Curcumin inhibits cell proliferation and induces apoptosis of human non-small cell lung cancer cells through the upregulation of miR-192-5p and suppression of PI3K/Akt signaling pathway. Oncol Rep 2015; 34: 2782-89.
  • 27. Jin Z, El-Deiry WS. Overview of cell death signaling pathways. Cancer Biol Ther 2005; 4: 147-71.
  • 28. Giam M, Huang DCS. Bouillet, P. BH3-only proteins and their roles in programmed cell death. Oncogene 2008; 27: 128-36.
  • 29. Zuo L, Zhou T, Pannell BK, Ziegler AC, Best TM. Biological and physiological role of reactive oxygen species–the good, the bad and the ugly. Acta Physiol 2015; 214: 329-48.
  • 30. Zhu Y, Bu S. Curcumin induces autophagy, apoptosis, and cell cycle arrest in human pancreatic cancer cells. Evid Based Complementary Altern Med 2017; 2017.
  • 31. Larasati YA, Yoneda-Kato N, Nakamae I, Yokoyama T, Meiyanto E, Kato JY. Curcumin targets multiple enzymes involved in the ROS metabolic pathway to suppress tumor cell growth. Sci Rep 2018; 8: 1-13.
  • 32. Chen Q, Wang Y, Xu K, Lu G, Ying Z, Wu L, et al. Curcumin induces apoptosis in human lung adenocarcinoma A549 cells through a reactive oxygen species-dependent mitochondrial signaling pathway. Oncol Rep 2010; 23: 397-403.
  • 33. Kuttikrishnan S, Siveen KS, Prabhu KS, Khan AQ, Ahmed EI, Akhtar S, et al. Curcumin induces apoptotic cell death via inhibition of PI3-Kinase/AKT pathway in B- precursor acute lymphoblastic leukemia. Front Oncol 2019:9.
  • 34. Lu T, Zhu Z, Wu J, She H, Han R, Xu H, et al. DRAM1 regulates autophagy and cell proliferation via inhibition of the phosphoinositide 3-kinase-Akt-mTOR-ribosomal protein S6 pathway. Cell Commun Signal 2019; 17: 28.
  • 35. Johnson SM, Gulhati P, Arrieta I, Wang X, Uchida T, Gao T, et al. Curcumin inhibits proliferation of colorectal carcinoma by modulating Akt/mTOR signaling. Anticancer Res 2009; 29: 3185-3190.
  • 36. Shinojima N, Yokoyama T, Kondo Y, Kondo, S. Roles of the Akt/mTOR/p70S6K and ERK1/2 signaling pathways in curcumin-induced autophagy. Autophagy 2007; 3: 635-637.
  • 37. Moreau R, Kaur H. Curcumin and piperine inhibit mTORC1 signaling in intestinal epithelial cells. The FASEB Journal 2017; 31: 135-138.
  • 38. Srinivasula SM, Poyet JL, Razmara M, Datta P, Zhang Z, Alnemri ES. The PYRIN-CARD protein ASC is an activating adaptor for caspase-1. J Biol Chem 2002; 277: 21119-22.
There are 37 citations in total.

Details

Primary Language English
Journal Section Research Articles
Authors

Süleyman İlhan 0000-0002-6584-3979

Publication Date December 25, 2020
Submission Date April 9, 2020
Published in Issue Year 2020 Volume: 79 Issue: 2

Cite

AMA İlhan S. Profile of Apoptotic Proteins After Curcumin Treatment by Antibody Array in H69AR Lung Cancer Cells. Eur J Biol. December 2020;79(2):157-162.