Facile green synthesis of nano-sized ZnO using leaf extract of Morinda tinctoria: MCF-7 cell cycle arrest, antiproliferation, and apoptosis studies

Jaganathan Anitha; Rajendran Selvakumar; Senthilnayagam Hema; Kadarkarai Murugan; Thathan Premkumar

Journal of Industrial and Engineering Chemistry, Vol.105, 520-529, January, 2022

DOI10.1016/j.jiec.2021.10.008 Export Citation

Facile green synthesis of nano-sized ZnO using leaf extract of Morinda tinctoria: MCF-7 cell cycle arrest, antiproliferation, and apoptosis studies

Jaganathan Anitha^†, Rajendran Selvakumar¹, Senthilnayagam Hema², Kadarkarai Murugan³, and Thathan Premkumar^{4, †}

Department of Biochemistry, Kongunadu Arts and Science College (Autonomous), Coimbatore, Tamil Nadu 641029, India
¹Department of Science and Humanities, Sri Krishna Polytechnic College, Coimbatore, Tamil Nadu 641042, India
²Department of Chemistry, Government College of Technology, Coimbatore, Tamil Nadu 641013, India
³Department of Zoology, Bharathiar University, School of Life Science, Coimbatore, Tamil Nadu 641046, India
⁴The University College, Department of Chemistry, Sungkyunkwan University, Suwon, Gyeonggi 16419, Republic of Korea

E-mail:,

Zinc oxide nanoparticles (ZnO NPs) were prepared by a facile, one-pot, greener approach using aqueous leaf extract of the medicinal plant Nuna (Morinda tinctoria) and were analyzed by ultraviolet.visible (UV-Vis) and Fourier-transform infrared (FT-IR) spectroscopy, powder X-ray diffraction (PXRD), field emission scanning electron microscopy (FESEM), and transmission electron microscopy (TEM) techniques. The TEM images confirmed that the as-prepared greener Nuna (Nu)-mediated ZnO NPs (Nu-ZnO NPs) were spherical in shape, with an average diameter of 8-10 nm. Further, the single phase and crystallinity of the Nu-ZnO NPs were observed by PXRD pattern. In addition, the biogenic Nu-ZnO NPs showed high cytotoxicity in human breast adenocarcinoma (MCF-7) cells in vitro. These tiny spherical bodies produced profound toxicity according to the MTT assay, with IC50 of 46 μg/mL. Apoptosis and morphological changes were studied using acridine orange/ethidium bromide and 4',6-diamidino-2-phenylindole fluorescence staining and MTT assays. Finally, the anticancer efficacy of biosynthesized Nu-ZnO NPs was imparted by dysregulation of cell division through arrest of growth-promoting and inhibiting signals in the S phase, with further reduction in the G2/M phase of the cell cycle. In conclusion, Nu-ZnO NPs conferred MCF-7 cell toxicity by modulating proliferation and inducing apoptosis.

Keywords:Breast cancer;Green synthesis;Morinda tinctoria;Nuna;Zinc oxide nanoparticles

[References]

Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, Cancer J. Clin., 61, 69 (2011)
Peto R, Boreham J, Clarke M, Davies C, Beral V, The Lancet, 355, 9217 (2000)
Hortobagyi GN, Eur. J. Cancer Suppl., 1, 23 (2003)
Laplane L, Duluc D, Bikfalvi A, Larmonier N, Pradeu T, Int. J. Cancer, 145, 2611 (2019)
Gurunathan S, Han JW, Dayem AA, Eppakayala V, Park JH, Cho SG, Lee KJ, Kim JH, J. Ind. Eng. Chem., 19(5), 1600 (2013)
Al-Suhaibani ES, El-Morshedi NA, IOSR J. Pharm. Biol. Sci., 9, 05 (2014)
Jin T, Sun D, Su JY, Zhang H, Sue HJ, J. Food Sci., 74, M46 (2009)
Rahman A, Harunsani MH, Tan AL, Khan MM, Bioprocess Biosyst. Eng., 44, 1333 (2021)
Wahaba R, Kima YS, Hwangb IH, Shin HS, Synth. Met., 159, 2443 (2009)
Kim JS, Jo SD, Seah GL, Kim I, Nam YS, J. Ind. Eng. Chem., 21, 1137 (2014)
Rahman A, Harunsani MH, Tan AL, Ahmad N, Hojamberdiev M, Khan MM, Bioprocess Biosyst. Eng., 44, 875 (2021)
Rahman A, Harunsani MH, Tan AL, Ahmad N, Min BK, Khan MM, Mater. Sci. Semicond. Process, 128 (2021)
Rahman A, Harunsani MH, Tan AL, Ahmad N, Khan MM, Chem. Pap., 75, 3295 (2021)
Wang B, Feng WY, Wang TC, Jia G, Wang M, Shi JW, Zhang F, Zhao YL, Chai ZF, Toxicol. Lett., 161, 115 (2006)
Jayaseelan C, Rahuman AA, Kirthi AV, Marimuthua S, Santhoshkumara T, Bagavana A, Spectroc. Acta Pt. A-Molec. Biomolec. Spectr., 90, 78 (2012)
Gopinath K, Shanmugam VK, Gowri S, Senthilkumar V, Kumaresan S, Arumugam A, J. Nanostruct. Chem., 4, 83 (2014)
Huang J, Li Q, Sun D, Lu Y, Su Y, Yang X, Nanotechnology, 18, 105104 (2007)
Behzad F, Naghib SM, kouhbanani MAJ, Tabatabaei SN, Zare Y, Rhee KY, J. Ind. Eng. Chem., 94, 92 (2021)
Vasantharaj S, Sathiyavimal S, Senthilkumar P, Kalpana VN, Rajalakshmi G, Alsehli M, Elfasakhany A, Pugazhendh A, J. Environ. Chem. Eng., 9 (2021)
Mittal AK, Chisti Y, Banerjee UC, Biotechnol. Adv., 31, 346 (2013)
Iravani S, Green Chem., 13, 2638 (2011)
Mathivanan N, Surendiran G, Srinivasan K, Malarvizhi K, J. Med. Food, 9, 591 (2006)
Kumaresan PT, Saravanan A, Afr. J. Pharm. Pharmacol., 3, 63 (2009)
George TW, Niwat C, Waroonphan S, Gordon MH, Lovegrove JA, Proc. Nutr. Soc., 68, 148 (2009)
Liu RH, Am. J. Clin. Nutr., 78, 517S (2003)
Upadhyay S, Dixit M, Oxid. Med. Cell. Longev. (2005).
Rao GV, Rao PS, J. Indian Chem. Soc., 60, 585 (1983)
Subramanian SS, Nair AGR, Phytochemistry, 10, 2125 (1971)
Sahoo AK, Narayanan N, Kumar NS, Rajan S, Mukherjee PK, Orient. Pharm. Exp. Med., 9, 101 (2009)
Rajkumar SRJ, Gnanavel G, Nadar MSAM, Sankaranarayanan S, Biotechnology, 8, 343 (2018)
Arunachalam KD, Kuruva JK, Hari S, Annamalai SK, Baskaran KV, Int. J. Pharm. Pharm. Sci., 7, 360 (2015)
Mosmann T, J. Immunol. Methods, 65, 55 (1983)
Thangam R, Senthilkumar D, Suresh V, Sathuvan M, Sivasubramanian S, Pazhanichamy K, Kannan S, Rengasamy R, Sivaraman J, J. Agric. Food Chem., 62, 3410 (2014)
Al-Dhabi NA, Arasu MV, Nanomaterials, 8, 500 (2018)
Fooladsaz K, Negahdary M, Rahimi G, Habibi-Tamijani A, Parsania S, Akbari-dastjerdi H, Sayad A, Jamaleddini A, Salahi F, Asadi A, Int. J. Electrochem. Sci., 7, 9892 (2012)
Ramalingam V, Hwang IH, J. Ind. Eng. Chem., 83, 315 (2020)
Fu M, Wang C, Li Z, Sakamaki T, Pestell RG, Endocrinology, 145, 5439 (2004)
Bagwe RP, Khilar KC, Langmuir, 16(3), 905 (2000)
Baishya D, Sharma N, Bora R, Arch. Appl. Sci. Res., 4, 2098 (2012)
Paramasivam G, Kannan R, Paulraj SM, Pandiarajan J, Pharm. Biol. Eval., 4, 222 (2017)
Al-Nassara SI, Husseinb FI, Adel KM, J. Mater. Res. Technol., 8, 4026 (2019)
Note OP, Jihu D, Antheaume C, Carbohydr. Res., 404, 26 (2015)
Umar H, Kavaz D, Rizaner N, Int. J. Nanomed., 14, 87 (2018)
Yu JH, Du YM, Zheng H, Wuhan Univ. J. Nat. Sci., 45, 440 (1999)
Hettiarachchi MA, Wickramarachchi PASR, J. Sci. Univ. Kelaniya, 6, 65 (2011)
Radhakrishnan R, Ali Khan FL, Muthu A, Manokaran A, Savarenathan JS, Kasinathan K, Lett. Appl. NanoBioSci., 10, 2706 (2021)
Guo J, Wu H, Liao X, Shi B, J. Phys. Chem. C, 115, 23688 (2011)
Suman TY, Rajasree SRR, Kanchana A, Elizabeth SB, Colloids Surf. B: Biointerfaces, 106, 74 (2013)
Yoon JS, Oh SG, J. Ind. Eng. Chem., 96, 390 (2021)
Ranoszek-Soliwoda K, Tomaszewska E, Socha E, Krzyczmonik P, Ignaczak A, Orlowski P, Krzyzowska M, Celichowski G, Grobelny J, J. Nanoparticle Res., 19, 273 (2017)
Rahman A, Tan AL, Harunsani MH, Ahmad N, Hojamberdiev M, Khan MM, J. Environ. Chem. Eng., 9 (2021)
Talam S, Karumuri SR, Gunnam N, ISRN Nanotechnol., 6, 505 (2012)
Raut S, Thorat PV, Thakare R, Int. J. Sci. Res., 4, 1225 (2013)
Chaudhuri SK, Malodia L, Appl. Nanosci., 7, 501 (2017)
Suriyakalaa U, Antony JJ, Suganya S, Siva D, Sukirtha R, Kamalakkannan S, Colloids Surf. B: Biointerfaces, 102, 189 (2013)
Niazvand F, Orazizadeh M, Khorsandi L, Abbaspour M, Mansouri E, Khodadadi A, Medicina, 55, 114 (2011)
Anitha A, Ramesh KV, Ravishankar TN, Sudheerkumar KH, Ramakrishnappa T, J. Sci.: Adv. Mater. Dev., 3, 440 (2018)
Pick E, Mizel D, J. Immunol. Methods, 46, 211 (1981)
Hussain A, Oves M, Alajmi MF, Hussain I, Amir S, Ahmed J, Rehman T, El-Seedif HR, Imran AI, RSC Adv., 27, 15357 (2019)
Anitha J, Selvakumar R, Murugan K, Int. J. Biol. Macromol., 136, 686 (2019)
Alavi M, Karimi N, Salimikia I, J. Ind. Eng. Chem., 72, 457 (2019)
Stewart ZA, Westfall MD, Pietenpol JA, Trends Pharmacol Sci., 24, 139 (2003)
Garrett MD, Curr. Sci., 81, 515 (2001)
Alao JP, Mol. Cancer, 6, 24 (2004)
Foster DA, Yellen P, Xu L, Saqcena M, Genes Cancer, 1, 1124 (2010)
Yaacob NS, Kamal NM, Wong KK, Norazmi MN, Asian Pac. J. Cancer Prev., 16, 8135 (2015)

[1] Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D, Cancer J. Clin., 61, 69 (2011)

[2] Peto R, Boreham J, Clarke M, Davies C, Beral V, The Lancet, 355, 9217 (2000)

[3] Hortobagyi GN, Eur. J. Cancer Suppl., 1, 23 (2003)

[4] Laplane L, Duluc D, Bikfalvi A, Larmonier N, Pradeu T, Int. J. Cancer, 145, 2611 (2019)

[5] Gurunathan S, Han JW, Dayem AA, Eppakayala V, Park JH, Cho SG, Lee KJ, Kim JH, J. Ind. Eng. Chem., 19(5), 1600 (2013)

[6] Al-Suhaibani ES, El-Morshedi NA, IOSR J. Pharm. Biol. Sci., 9, 05 (2014)

[7] Jin T, Sun D, Su JY, Zhang H, Sue HJ, J. Food Sci., 74, M46 (2009)

[8] Rahman A, Harunsani MH, Tan AL, Khan MM, Bioprocess Biosyst. Eng., 44, 1333 (2021)

[9] Wahaba R, Kima YS, Hwangb IH, Shin HS, Synth. Met., 159, 2443 (2009)

[10] Kim JS, Jo SD, Seah GL, Kim I, Nam YS, J. Ind. Eng. Chem., 21, 1137 (2014)

[11] Rahman A, Harunsani MH, Tan AL, Ahmad N, Hojamberdiev M, Khan MM, Bioprocess Biosyst. Eng., 44, 875 (2021)

[12] Rahman A, Harunsani MH, Tan AL, Ahmad N, Min BK, Khan MM, Mater. Sci. Semicond. Process, 128 (2021)

[13] Rahman A, Harunsani MH, Tan AL, Ahmad N, Khan MM, Chem. Pap., 75, 3295 (2021)

[14] Wang B, Feng WY, Wang TC, Jia G, Wang M, Shi JW, Zhang F, Zhao YL, Chai ZF, Toxicol. Lett., 161, 115 (2006)

[15] Jayaseelan C, Rahuman AA, Kirthi AV, Marimuthua S, Santhoshkumara T, Bagavana A, Spectroc. Acta Pt. A-Molec. Biomolec. Spectr., 90, 78 (2012)

[16] Gopinath K, Shanmugam VK, Gowri S, Senthilkumar V, Kumaresan S, Arumugam A, J. Nanostruct. Chem., 4, 83 (2014)

[17] Huang J, Li Q, Sun D, Lu Y, Su Y, Yang X, Nanotechnology, 18, 105104 (2007)

[18] Behzad F, Naghib SM, kouhbanani MAJ, Tabatabaei SN, Zare Y, Rhee KY, J. Ind. Eng. Chem., 94, 92 (2021)

[19] Vasantharaj S, Sathiyavimal S, Senthilkumar P, Kalpana VN, Rajalakshmi G, Alsehli M, Elfasakhany A, Pugazhendh A, J. Environ. Chem. Eng., 9 (2021)

[20] Mittal AK, Chisti Y, Banerjee UC, Biotechnol. Adv., 31, 346 (2013)

[21] Iravani S, Green Chem., 13, 2638 (2011)

[22] Mathivanan N, Surendiran G, Srinivasan K, Malarvizhi K, J. Med. Food, 9, 591 (2006)

[23] Kumaresan PT, Saravanan A, Afr. J. Pharm. Pharmacol., 3, 63 (2009)

[24] George TW, Niwat C, Waroonphan S, Gordon MH, Lovegrove JA, Proc. Nutr. Soc., 68, 148 (2009)

[25] Liu RH, Am. J. Clin. Nutr., 78, 517S (2003)

[26] Upadhyay S, Dixit M, Oxid. Med. Cell. Longev. (2005).

[27] Rao GV, Rao PS, J. Indian Chem. Soc., 60, 585 (1983)

[28] Subramanian SS, Nair AGR, Phytochemistry, 10, 2125 (1971)

[29] Sahoo AK, Narayanan N, Kumar NS, Rajan S, Mukherjee PK, Orient. Pharm. Exp. Med., 9, 101 (2009)

[30] Rajkumar SRJ, Gnanavel G, Nadar MSAM, Sankaranarayanan S, Biotechnology, 8, 343 (2018)

[31] Arunachalam KD, Kuruva JK, Hari S, Annamalai SK, Baskaran KV, Int. J. Pharm. Pharm. Sci., 7, 360 (2015)

[32] Mosmann T, J. Immunol. Methods, 65, 55 (1983)

[33] Thangam R, Senthilkumar D, Suresh V, Sathuvan M, Sivasubramanian S, Pazhanichamy K, Kannan S, Rengasamy R, Sivaraman J, J. Agric. Food Chem., 62, 3410 (2014)

[34] Al-Dhabi NA, Arasu MV, Nanomaterials, 8, 500 (2018)

[35] Fooladsaz K, Negahdary M, Rahimi G, Habibi-Tamijani A, Parsania S, Akbari-dastjerdi H, Sayad A, Jamaleddini A, Salahi F, Asadi A, Int. J. Electrochem. Sci., 7, 9892 (2012)

[36] Ramalingam V, Hwang IH, J. Ind. Eng. Chem., 83, 315 (2020)

[37] Fu M, Wang C, Li Z, Sakamaki T, Pestell RG, Endocrinology, 145, 5439 (2004)

[38] Bagwe RP, Khilar KC, Langmuir, 16(3), 905 (2000)

[39] Baishya D, Sharma N, Bora R, Arch. Appl. Sci. Res., 4, 2098 (2012)

[40] Paramasivam G, Kannan R, Paulraj SM, Pandiarajan J, Pharm. Biol. Eval., 4, 222 (2017)

[41] Al-Nassara SI, Husseinb FI, Adel KM, J. Mater. Res. Technol., 8, 4026 (2019)

[42] Note OP, Jihu D, Antheaume C, Carbohydr. Res., 404, 26 (2015)

[43] Umar H, Kavaz D, Rizaner N, Int. J. Nanomed., 14, 87 (2018)

[44] Yu JH, Du YM, Zheng H, Wuhan Univ. J. Nat. Sci., 45, 440 (1999)

[45] Hettiarachchi MA, Wickramarachchi PASR, J. Sci. Univ. Kelaniya, 6, 65 (2011)

[46] Radhakrishnan R, Ali Khan FL, Muthu A, Manokaran A, Savarenathan JS, Kasinathan K, Lett. Appl. NanoBioSci., 10, 2706 (2021)

[47] Guo J, Wu H, Liao X, Shi B, J. Phys. Chem. C, 115, 23688 (2011)

[48] Suman TY, Rajasree SRR, Kanchana A, Elizabeth SB, Colloids Surf. B: Biointerfaces, 106, 74 (2013)

[49] Yoon JS, Oh SG, J. Ind. Eng. Chem., 96, 390 (2021)

[50] Ranoszek-Soliwoda K, Tomaszewska E, Socha E, Krzyczmonik P, Ignaczak A, Orlowski P, Krzyzowska M, Celichowski G, Grobelny J, J. Nanoparticle Res., 19, 273 (2017)

[51] Rahman A, Tan AL, Harunsani MH, Ahmad N, Hojamberdiev M, Khan MM, J. Environ. Chem. Eng., 9 (2021)

[52] Talam S, Karumuri SR, Gunnam N, ISRN Nanotechnol., 6, 505 (2012)

[53] Raut S, Thorat PV, Thakare R, Int. J. Sci. Res., 4, 1225 (2013)

[54] Chaudhuri SK, Malodia L, Appl. Nanosci., 7, 501 (2017)

[55] Suriyakalaa U, Antony JJ, Suganya S, Siva D, Sukirtha R, Kamalakkannan S, Colloids Surf. B: Biointerfaces, 102, 189 (2013)

[56] Niazvand F, Orazizadeh M, Khorsandi L, Abbaspour M, Mansouri E, Khodadadi A, Medicina, 55, 114 (2011)

[57] Anitha A, Ramesh KV, Ravishankar TN, Sudheerkumar KH, Ramakrishnappa T, J. Sci.: Adv. Mater. Dev., 3, 440 (2018)

[58] Pick E, Mizel D, J. Immunol. Methods, 46, 211 (1981)

[59] Hussain A, Oves M, Alajmi MF, Hussain I, Amir S, Ahmed J, Rehman T, El-Seedif HR, Imran AI, RSC Adv., 27, 15357 (2019)

[60] Anitha J, Selvakumar R, Murugan K, Int. J. Biol. Macromol., 136, 686 (2019)

[61] Alavi M, Karimi N, Salimikia I, J. Ind. Eng. Chem., 72, 457 (2019)

[62] Stewart ZA, Westfall MD, Pietenpol JA, Trends Pharmacol Sci., 24, 139 (2003)

[63] Garrett MD, Curr. Sci., 81, 515 (2001)

[64] Alao JP, Mol. Cancer, 6, 24 (2004)

[65] Foster DA, Yellen P, Xu L, Saqcena M, Genes Cancer, 1, 1124 (2010)

[66] Yaacob NS, Kamal NM, Wong KK, Norazmi MN, Asian Pac. J. Cancer Prev., 16, 8135 (2015)