Abstract
Colorectal cancer (CRC) progression is a complex process, with an interplay of multiple molecular signaling pathways. Cyclooxygenase-2 (COX-2) and NF-κB are important hallmark proteins responsible for the transition from inflammation to colon cancer. Due to the adverse effects of chemotherapeutic drugs, there is an imperative need to develop new drugs, and recently, nanoparticles found to be promising strategy in tumor detection, prevention and treatment of cancer. Biosynthesis of silver nanoparticles (AgNPs) was achieved with the help of Eucalyptus globulus L. leaf extract. Using a typical XRD pattern, NanoSight and TEM technique, the size and shape of the biogenic AgNPs were determined as ~ 20 nm and spherical. The cytotoxicity study exhibited a dose-dependent effect against HCT116 cells, with an inhibitory concentration (IC50) of 1.152 µg/ml. In addition, AgNPs effectively inhibited the proliferation, colony formation, with increased ROS production compared to untreated cells. Further, mechanistic analysis revealed that AgNPs arrested the cell cycle, downregulated the expression of antiapoptotic, inflammatory, stem cell markers, and upregulated the apoptotic genes in HCT116 cells. In conclusion, for the first time, we report the green synthesis of AgNPs using E. globulus leaf extract that has potential anticancer activity with dual inhibitory action on COX-2 and NF-κB expression.
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References
J. Ferlay, M. Colombet, I. Soerjomataram, C. Mathers, D. M. Parkin, M. Piñeros, A. Znaor, and F. Bray (2019). Int J Cancer 144, 1941.
Y. Sasaki, D. Kamei, Y. Ishikawa, T. Ishii, S. Uematsu, S. Akira, M. Murakami, and S. Hara (2012). Oncogene 31, 2943.
M. M. Taketo (1998). J Natl Cancer Inst 90, 1609.
D. Wang and R. N. Dubois (2010). Oncogene 29, 781.
D. A. Dixon (2003). Prog Exp Tumor Res 37, 52.
T. J. Maier, K. Schilling, R. Schmidt, G. Geisslinger, and S. Grosch (2004). Biochem Pharmacol 67, 1469.
M. Karin, Y. Cao, F. R. Greten, and Z. W. Li (2002). Nat Rev Cancer 2, 301.
H. Clevers (2004). Cell 118, 671.
D. S. Lind, S. N. Hochwald, J. Malaty, S. Rekkas, P. Hebig, G. Mishra, L. L. Moldawer, E. M. Copeland 3rd., and S. Mackay (2001). Surgery 130, 363.
H. G. Yu, L. L. Yu, Y. Yang, H. S. Luo, J. P. Yu, J. J. Meier, H. Schrader, A. Bastian, W. E. Schmidt, and F. Schmitz (2003). Oncology 65, 37.
M. Abdullah, A. A. Rani, A. W. Sudoyo, D. Makmun, D. R. Handjari, and B. S. Hernowo (2013). Acta Med Indones 45, 187.
M. D. Haag, M. J. Bos, A. Hofman, P. J. Koudstaal, M. M. Breteler, and B. H. Stricker (2008). Arch Intern Med 168, 1219.
E. Z. Dajani and K. Islam (2008). J Physiol Pharmacol 59 (Suppl 2), 117.
M. Rai, A. Yadav, and A. Gade (2009). Biotechnol Adv 27, 76.
S. M. Mousavi, S. A. Hashemi, Y. Ghasemi, A. Atapour, A. M. Amani, A. Savar Dashtaki, A. Babapoor, and O. Arjmand (2018). Artif Cells Nanomed Biotechnol 46, S855.
S. P. Deshmukh, S. M. Patil, S. B. Mullani, and S. D. Delekar (2019). Mater Sci Eng C Mater Biol Appl 97, 954.
G. Das, J. K. Patra, T. Debnath, A. Ansari, and H.-S. Shin (2019). PLOS ONE 14, e0220950.
M. V. Yezhelyev, X. Gao, Y. Xing, A. Al-Hajj, S. Nie, and R. M. O’Regan (2006). Lancet Oncol 7, 657.
K. Vasanth, K. Ilango, R. MohanKumar, A. Agrawal, and G. P. Dubey (2014). Colloids Surf B Biointerfaces 117, 354.
Rz. M. Gengan, K. Anand, A. Phulukdaree, and A. Chuturgoon (2013). Colloids Surf B Biointerfaces 105, 87.
R. Remya, S. R. Rajasree, L. Aranganathan, and T. Suman (2015). Biotechnol Rep 8, 110.
I. M. Chung, I. Park, K. Seung-Hyun, M. Thiruvengadam, and G. Rajakumar (2016). Nanoscale Res Lett 11, 40.
A. Lateef, S. A. Ojo, and J. A. Elegbede (2016). Nanotechnol Rev 5, 601.
I. A. Adelere and A. Lateef (2016). Nanotechnol Rev 5, 567.
Y. He, Z. Du, H. Lv, Q. Jia, Z. Tang, X. Zheng, K. Zhang, and F. Zhao (2013). Int J Nanomed 8, 1809.
A. N. M. Ali, S. M. Kareem, and A. Ghasemian (2020). J Gastrointest Cancer 51, 560.
A. Nakhaee, M. Bokaeian, M. Saravani, A. Farhangi, and A. Akbarzadeh (2009). Indian J Clin Biochem 24, 419.
B. C. Zhu, G. Henderson, F. Chen, H. Fei, and R. A. Laine (2001). J Chem Ecol 27, 1617.
L. Mirossay, L. Varinská, and J. Mojžiš (2017). Int J Mol Sci 19, 27.
S. J. Jeong, W. Koh, E. O. Lee, H. J. Lee, H. Bae, J. Lü, and S. H. Kim (2011). Phytother Res 25, 1.
M. Rafique, I. Sadaf, M. S. Rafique, and M. B. Tahir (2017). Artif Cells Nanomed Biotechnol 45, 1272.
M. Khan, S. F. Adil, M. N. Tahir, W. Tremel, H. Z. Alkhathlan, A. Al-Warthan, and M. R. Siddiqui (2013). Int J Nanomed 8, 1507.
P. Kumar, A. Nagarajan, and P. D. Uchil (2018). Cold Spring Harb Protoc. https://doi.org/10.1101/pdb.prot095489.
F. Raeisi, E. Raeisi, E. Heidarian, D. Shahbazi-Gahroui, and Y. Lemoigne (2019). J Med Signals Sens 9, 267.
T. Ishiwata, F. Hasegawa, M. Michishita, N. Sasaki, N. Ishikawa, K. Takubo, Y. Matsuda, T. Arai, and J. Aida (2018). Oncol Lett 15, 2485.
D. Figueroa, M. Asaduzzaman, and F. Young (2018). J Pharmacol Toxicol Methods 94, 26.
L. C. Crowley, G. Chojnowski, and N. J. Waterhouse (2016). Cold Spring Harb Protoc. https://doi.org/10.1101/pdb.prot087163.
B. Kim (2017). Methods Mol Biol 1606, 133.
K. Ali, B. Ahmed, S. Dwivedi, Q. Saquib, A. A. Al-Khedhairy, and J. Musarrat (2015). PLoS One 10, e0131178.
P. Salgado, D. O. Mártire, and G. Vidal (2019). Mater Res Exp 6, 82006.
M. Riaz, M. Altaf, A. Faisal, M. A. Shekheli, G. A. Miana, M. Q. Khan, M. A. Shah, S. Z. Ilyas, and A. A. Khan (2018). J Nanosci Nanotechnol 18, 8392.
S. B. Aziz, G. Hussein, M. A. Brza, S. J. Mohammed, R. T. Abdulwahid, S. R. Saeed, and A. Hassanzadeh (2019). Nanomaterials (Basel) 9.
S. Pirtarighat, M. Ghannadnia, and S. Baghshahi (2019). Mater Sci Eng C Mater Biol Appl 98, 250.
A. R. Allafchian, S. A. H. Jalali, F. Aghaei, and H. R. Farhang (2018). IET Nanobiotechnol 12, 574.
P. Kuppusamy, S. J. Ichwan, P. N. Al-Zikri, W. H. Suriyah, I. Soundharrajan, N. Govindan, G. P. Maniam, and M. M. Yusoff (2016). Biol Trace Elem Res 173, 297.
S. K. Verma, E. Jha, P. K. Panda, A. Mishra, A. Thirumurugan, B. Das, S. K. S. Parashar, and M. Suar (2018). Toxicol Sci 161, 125.
S. Deepika, C. I. Selvaraj, and S. M. Roopan (2020). Mater Sci Eng C Mater Biol Appl 106, 110279.
H. Xiao, Y. Chen, and M. Alnaggar (2019). Micron 126, 102750.
S. Gurunathan, M. Qasim, C. Park, H. Yoo, J. H. Kim, and K. Hong (2018). Int J Mol Sci 19, 2269.
C. W. Lee, M. J. Chen, J. Y. Cheng, and P. K. Wei (2009). J Biomed Opt 14, 34016.
L. de la Garza, Z. V. Saponjic, N. M. Dimitrijevic, M. C. Thurnauer, and T. Rajh (2006). J Phys Chem B 110, 1.
T. Sree Latha, M. C. Reddy, S. V. Muthukonda, V. Srikanth, and D. Lomada (2017). Mater Sci Eng C Mater Biol Appl 78, 969.
S. R. Satapathy, P. Mohapatra, D. Das, S. Siddharth, and C. N. Kundu (2015). Pathol Oncol Res 21, 405.
S. R. Satapathy, P. Mohapatra, R. Preet, D. Das, B. Sarkar, T. Choudhuri, M. D. Wyatt, and C. N. Kundu (2013). Nanomedicine (Lond) 8, 1307.
S. Holdenrieder and P. Stieber (2004). Clin Biochem 37, 605.
T. Komiya, Y. Hosono, T. Hirashima, N. Masuda, T. Yasumitsu, K. Nakagawa, M. Kikui, A. Ohno, M. Fukuoka, and I. Kawase (1997). Clin Cancer Res 3, 1831.
A. V. Biankin, J. G. Kench, A. L. Morey, C. S. Lee, S. A. Biankin, D. R. Head, T. B. Hugh, S. M. Henshall, and R. L. Sutherland (2001). Cancer Res 61, 8830.
Y. Q. Bai, S. Miyake, T. Iwai, and Y. Yuasa (2003). Oncogene 22, 7942.
A. N. Hata, J. A. Engelman, and A. C. Faber (2015). Cancer Discov 5, 475.
P. E. Czabotar, G. Lessene, A. Strasser, and J. M. Adams (2014). Nat Rev Mol Cell Biol 15, 49.
T. Dziaman, H. Ludwiczak, J. M. Ciesla, Z. Banaszkiewicz, A. Winczura, M. Chmielarczyk, E. Wisniewska, A. Marszalek, B. Tudek, and R. Olinski (2014). PLOS ONE 9, 115558.
I. Bièche, G. de Murcia, and R. Lidereau (1996). Clin Cancer Res 2, 1163.
K. Nosho, H. Yamamoto, M. Mikami, H. Taniguchi, T. Takahashi, Y. Adachi, A. Imamura, K. Imai, and Y. Shinomura (2006). Eur J Cancer 42, 2374.
R. Jäger and R. M. Zwacka (2010). Cancers (Basel) 2, 1952.
A. Philchenkov, M. Zavelevich, T. J. Kroczak, and M. Los (2004). Exp Oncol 26, 82.
M. Asadi, D. Shanehbandi, T. Asvadi Kermani, Z. Sanaat, V. Zafari, and S. Hashemzadeh (2018). Asian Pac J Cancer Prev 19, 1277.
N. N. Danial and S. J. Korsmeyer (2004). Cell 116, 205.
V. R. Katkoori, C. Suarez-Cuervo, C. Shanmugam, N. C. Jhala, T. Callens, L. Messiaen, J. Posey 3rd., H. L. Bumpers, S. Meleth, W. E. Grizzle, and U. Manne (2010). J Gastrointest Oncol 1, 76.
A. Pryczynicz, M. Gryko, K. Niewiarowska, D. Cepowicz, M. Ustymowicz, A. Kemona, and K. Guzińska-Ustymowicz (2014). World J Gastroenterol 20, 1305.
R. Fux, M. Schwab, K. P. Thon, C. H. Gleiter, and P. Fritz (2005). Clin Cancer Res 11, 4754.
C. E. Eberhart, R. J. Coffey, A. Radhika, F. M. Giardiello, S. Ferrenbach, and R. N. DuBois (1994). Gastroenterology 107, 1183.
B. Hoesel and J. A. Schmid (2013). Mol Cancer 12, 86.
N. Moorchung, S. Kunwar, and K. W. Ahmed (2014). J Cancer Res Ther 10, 631.
Y. Xia, S. Shen, and I. M. Verma (2014). Cancer Immunol Res 2, 823.
R. Pang, W. L. Law, A. C. Chu, J. T. Poon, C. S. Lam, A. K. Chow, L. Ng, L. W. Cheung, X. R. Lan, H. Y. Lan, V. P. Tan, T. C. Yau, R. T. Poon, and B. C. Wong (2010). Cell Stem Cell 6, 603.
Z. Kozovska, V. Gabrisova, and L. Kucerova (2014). Biomed Pharmacother 68, 911.
S. Saigusa, K. Tanaka, Y. Toiyama, K. Matsushita, M. Kawamura, Y. Okugawa, J. Hiro, Y. Inoue, K. Uchida, Y. Mohri, and M. Kusunoki (2012). Oncol Rep 28, 855.
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This work was partly supported by the Science and Engineering Research Board (SERB) (EMR/2017/000973), Department of Science & Technology, Government of India.
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Narasimha, V.R., Latha, T.S., Pallu, R. et al. Anticancer Activities of Biogenic Silver Nanoparticles Targeting Apoptosis and Inflammatory Pathways in Colon Cancer Cells. J Clust Sci 33, 2215–2231 (2022). https://doi.org/10.1007/s10876-021-02143-z
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DOI: https://doi.org/10.1007/s10876-021-02143-z