Research Article
BibTex RIS Cite

In Vitro Evaluation of the Antineoplastic Activity of Silver Nanoparticles Functionalized with Bioactive Molecules Against SK-MEL-30, MCF-7, and H1299 Cancer Cells

Year 2025, Volume: 17 Issue: 3, 590 - 603, 30.11.2025
https://doi.org/10.29137/ijerad.1674277

Abstract

The present study aimed to evaluate the in vitro antineoplastic activity of silver nanoparticles (AgNPs) biosynthesized using Centella asiatica (CA) leaf extract against human SK-MEL-30 skin cancer, MCF-7 breast cancer, and H1299 lung cancer cell lines. CA/AgNPs were synthesized via a green chemistry approach and characterized by standard physicochemical techniques. The anticancer potential of the synthesized nanoparticles was assessed using MTT assays, along with apoptotic and necrotic index evaluations. Results indicated a dose-dependent reduction in cell viability in all cancer cell lines, while minimal cytotoxicity was observed in normal L929 fibroblast cells. Notably, CA and CA/AgNPs induced apoptosis and necrosis selectively in cancer cells, suggesting that both formulations possess strong antitumoral effects. The apoptotic indices were especially high in H1299 lung cancer cells treated with CA extract, whereas necrosis was most pronounced in SK-MEL-30 cells at higher concentrations. Taken together, these findings support the antineoplastic, anticancer, and cytotoxic potential of CA/AgNPs, highlighting their promise as biocompatible agents for targeted cancer therapies. Further in vivo studies are recommended to validate these effects.

Thanks

The author is grateful to Kırıkkale University and Kırıkkale University Scientific and Technological Researches Application and Research Center (KUBTUAM) for their support.

References

  • Abdulla, M., Al-Bayaty, F., Younis, L., & Abu Hassan, M. (2010). Anti-ulcer activity of Centella asiatica leaf extract against ethanolinduced gastric mucosal injury in rats. Journal of medicinal plants research, 4(13), 1253-1259.
  • Akturk, O. (2020). Colloidal stability and biological activity evaluation of microbial exopolysaccharide levan-capped gold nanoparticles. Colloids and Surfaces B: Biointerfaces, 192, 111061. https://doi.org/https://doi.org/10.1016/j.colsurfb.2020.111061
  • Albanese, A., Tang, P. S., & Chan, W. C. (2012). The effect of nanoparticle size, shape, and surface chemistry on biological systems. Annual Review of Biomedical Engineering, 14(1), 1-16.
  • Arribas-López, E., Zand, N., Ojo, O., Snowden, M. J., & Kochhar, T. (2022). A systematic review of the effect of Centella asiatica on wound healing. International Journal of Environmental Research and Public Health, 19(6), 3266.
  • Begum, R., Farooqi, Z. H., Naseem, K., Ali, F., Batool, M., Xiao, J., & Irfan, A. (2018). Applications of UV/Vis spectroscopy in characterization and catalytic activity of noble metal nanoparticles fabricated in responsive polymer microgels: a review. Critical Reviews in Analytical Chemistry, 48(6), 503-516.
  • Bozkaya, E., Türk, M., Ekici, H., & Karahan, S. (2023). Investigation of the biocompatibility and in vivo wound healing effect of Cotinus coggygria extracts. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 1-12. https://doi.org/10.33988/auvfd.1217177
  • Bozkaya, O., Bozkaya, E., Ekici, H., Alçığır, M. E., Şahin, Y., Aytuna Çerçi, N., Karahan, S., Yiğitoğlu, M., & Vargel, İ. (2024). Evaluation of Burn Wound Healing Efficacy and Biocompatibility of Centella asiatica Mediated Synthesised AgNPs Loaded Hybrid Nanofiber Scaffold: In Vitro and In Vivo Studies. Macromolecular Materials and Engineering, 309(12), 2400186. https://doi.org/https://doi.org/10.1002/mame.202400186
  • Bozkaya, O., Ekici, H., GÜN GÖK, Z., Bozkaya, E., Ekici, S., Yiğitoğlu, M., & Vargel, İ. (2023). Investigation of the in vitro antibacterial, cytotoxic and in vivo analgesic effects of silver nanoparticles coated with Centella asiatica plant extract. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 70(1), 87-96. https://doi.org/https://doi.org/10.33988/auvfd.1014802
  • Bozkaya, O., Günay, K., Bozkaya, E., & Arslan, M. (2024). Poly (hexamethylene biguanide) immobilized non-absorbable and antimicrobial PET fiber for surgical suture applications: synthesis, characterization and in vitro cytocompatibility assessment. International Journal of Engineering Research and Development, 16(2), 778-791.
  • Carlson, C., Hussain, S. M., Schrand, A. M., K. Braydich-Stolle, L., Hess, K. L., Jones, R. L., & Schlager, J. J. (2008). Unique cellular interaction of silver nanoparticles: size-dependent generation of reactive oxygen species. The journal of physical chemistry B, 112(43),13608-13619.
  • Chithrani, B. D., Ghazani, A. A., & Chan, W. C. (2006). Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Letters, 6(4), 662-668.
  • Cohen, I. S., Mosher, M. B., O'Keefe, E. J., Klaus, S. N., & De Conti, R. C. (1973). Cutaneous toxicity of bleomycin therapy. Archives of Dermatology, 107(4), 553-555.
  • Dalkılıç, S., Kadıoğlu Dalkılıç, L., İsbenov, E., Uygur, L., & Taşdemir, C. (2025). Investigation of Cytotoxic, Antioxidant, Apoptotic/Necrotic Activity of Aquilaria agallocha Root Extract and Determination of Gene Expression Levels in HepG2, MCF-7 Cancer Cell Lines. Life, 15(4), 651.
  • Deka, D., Chakravarty, P., & Purkayastha, A. (2017). Evaluation of the anticonvulsant effect of aqueous extract of centella asiatica in albino mice. Int J Pharm Pharm Sci, 9(2), 312-314.
  • Desai, A. G., Qazi, G. N., Ganju, R. K., El-Tamer, M., Singh, J., Saxena, A. K., Bedi, Y. S., Taneja, S. C., & Bhat, H. K. (2008). Medicinal plants and cancer chemoprevention. Current Drug Metabolism, 9(7), 581-591. https://doi.org/10.2174/138920008785821657
  • Diaz, M. J., Natarelli, N., Aflatooni, S., Aleman, S. J., Neelam, S., Tran, J. T., Taneja, K., Lucke-Wold, B., & Forouzandeh, M. (2023). Nanoparticle-Based Treatment Approaches for Skin Cancer: A Systematic Review. Current Oncology (Toronto, Ont.), 30(8), 7112-7131. https://doi.org/10.3390/curroncol30080516
  • Duan, X., & Li, Y. (2013). Physicochemical characteristics of nanoparticles affect circulation, biodistribution, cellular internalization, and trafficking. Small, 9(9‐10), 1521-1532.
  • Ekici, S., Bozkaya, E., Bozkaya, O., Cerci, N. A., Aluc, Y., & Ekici, H. (2023). Vitex Agnus-Castus L. Nanoparticles: Preparation, Characterization and Assessment of Antimicrobial and Anticancer Activity. ChemistrySelect, 8(32), e202302102. https://doi.org/https://doi.org/10.1002/slct.202302102
  • Ekici, S., Bozkaya, O., Sevin, S., Erdem, B., Arslan, O. C., Özgenç Cinar, O., Bozkaya, E., & Ekici, H. (2024). Investigation of the biological activity and toxicity of bioactive silver nanoparticles synthesized via Vitex agnus-castus seed extract on honey bees. Veterinary Research Communications, 48(6), 3813-3821.
  • Fard, S. E., Tafvizi, F., & Torbati, M. B. (2018). Silver nanoparticles biosynthesised using Centella asiatica leaf extract: apoptosis induction in MCF-7 breast cancer cell line. IET Nanobiotechnology, 12(7), 994-1002. https://doi.org/https://doi.org/10.1049/ietnbt.2018.5069
  • Fernando, I., & Zhou, Y. (2019). Impact of pH on the stability, dissolution and aggregation kinetics of silver nanoparticles. Chemosphere, 216, 297-305.
  • George, M., & Joseph, L. (2009). Anti-allergic, anti-pruritic, and anti-inflammatory activities of Centella asiatica extracts. African Journal of Traditional, Complementary and Alternative Medicines, 6(4).
  • Gibaud, S., Andreux, J., Weingarten, C., Renard, M., & Couvreur, P. (1994). Increased bone marrow toxicity of doxorubicin bound to nanoparticles. European Journal of Cancer, 30(6), 820-826.
  • Gohil, K. J., Patel, J. A., & Gajjar, A. K. (2010). Pharmacological review on Centella asiatica: a potential herbal cure-all. Indian Journal of Pharmaceutical Sciences, 72(5), 546.
  • Graham, J., Quinn, M., Fabricant, D., & Farnsworth, N. (2000). Plants used against cancer–an extension of the work of Jonathan Hartwell. Journal of Ethnopharmacology, 73(3), 347-377.
  • Gratton, S. E., Ropp, P. A., Pohlhaus, P. D., Luft, J. C., Madden, V. J., Napier, M. E., & DeSimone, J. M. (2008). The effect of particle design on cellular internalization pathways. Proceedings of the National Academy of Sciences of the United States of America, 105(33), 11613-11618. https://doi.org/10.1073/pnas.0801763105
  • Gün Gök, Z., Günay, K., Arslan, M., Yiğitoğlu, M., & Vargel, İ. (2020). Coating of modified poly (ethylene terephthalate) fibers with sericin-capped silver nanoparticles for antimicrobial application. Polymer Bulletin, 77(4), 1649-1665.
  • Gün Gök, Z., Yiğitoğlu, M., Vargel, İ., Şahin, Y., & Alçığır, M. E. (2021). Synthesis, characterization and wound healing ability of PET based nanofiber dressing material coated with silk sericin capped-silver nanoparticles. Materials Chemistry and Physics, 259, 124043. https://doi.org/https://doi.org/10.1016/j.matchemphys.2020.124043
  • Hao, Y., Huang, J., Ma, Y., Chen, W., Fan, Q., Sun, X., Shao, M., & Cai, H. (2018). Asiatic acid inhibits proliferation, migration and induces apoptosis by regulating Pdcd4 via the PI3K/Akt/mTOR/p70S6K signaling pathway in human colon carcinoma cells. Oncology Letters, 15(6), 8223-8230.
  • Himalini, S., Nallal, V. U. M., Razia, M., Chinnapan, S., Chandrasekaran, M., Ranganathan, V., Gatasheh, M. K., Hatamleh, A. A., Al-Khattaf, F. S., & Kanimozhi, S. (2022). Antimicrobial, anti-melanogenesis and anti-tyrosinase potential of myco-synthesized silver nanoparticles on human skin melanoma SK-MEL-3 cells. Journal of King Saud University-Science, 34(3), 101882.
  • Hoshyar, N., Gray, S., Han, H., & Bao, G. (2016). The effect of nanoparticle size on in vivo pharmacokinetics and cellular interaction. Nanomedicine (Lond), 11(6), 673-692. https://doi.org/10.2217/nnm.16.5
  • Hsu, Y.-L., Kuo, P.-L., Lin, L.-T., & Lin, C.-C. (2005). Asiatic acid, a triterpene, induces apoptosis and cell cycle arrest through activation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase pathways in human breast cancer cells. The Journal of pharmacology and experimental therapeutics, 313(1), 333-344.
  • Jhansi, D., & Kola, M. (2019). The antioxidant potential of Centella asiatica: A review. J. Med. Plants Stud, 7, 18-20.
  • Jo, D. H., Kim, J. H., Lee, T. G., & Kim, J. H. (2015). Size, surface charge, and shape determine therapeutic effects of nanoparticles on brain and retinal diseases. Nanomedicine: Nanotechnology, Biology and Medicine, 11(7), 1603-1611.
  • Kandasamy, A., Aruchamy, K., Rangasamy, P., Varadhaiyan, D., Gowri, C., Oh, T. H., Ramasundaram, S., & Athinarayanan, B. (2023). Phytochemical analysis and antioxidant activity of Centella asiatica extracts: an experimental and theoretical investigation of flavonoids. Plants, 12(20), 3547.
  • Lian, G.-Y., Wang, Q.-M., Tang, P. M.-K., Zhou, S., Huang, X.-R., & Lan, H.-Y. (2018). Combination of asiatic acid and naringenin modulates NK cell anti-cancer immunity by rebalancing Smad3/Smad7 signaling. Molecular Therapy, 26(9), 2255-2266.
  • Macdonald, J. S. (1999). Toxicity of 5-fluorouracil. Oncology (Williston Park, NY), 13(7 Suppl 3), 33-34.
  • Manil, L., Mahieu, P., & Couvreur, P. (1995). Acute renal toxicity of doxorubicin (adriamycin)-loaded cyanoacrylate nanoparticles. Pharmaceutical Research, 12, 85-87.
  • Melekoğlu, A., Ekici, H., Esra, A., & Karahan, S. (2020). Evaluation of melamine and cyanuric acid cytotoxicity: an in vitro study on L929 fibroblasts and CHO cell line. Ankara Üniversitesi Veteriner Fakültesi Dergisi, 67(4), 399-406.
  • Moraru, C., Mincea, M., Menghiu, G., & Ostafe, V. (2020). Understanding the Factors Influencing Chitosan-Based NanoparticlesProtein Corona Interaction and Drug Delivery Applications. Molecules, 25(20), 4758. https://www.mdpi.com/1420-3049/25/20/4758
  • Németh, Z., Csóka, I., Semnani Jazani, R., Sipos, B., Haspel, H., Kozma, G., Kónya, Z., & Dobó, D. G. (2022). Quality by DesignDriven Zeta Potential Optimisation Study of Liposomes with Charge Imparting Membrane Additives. Pharmaceutics, 14(9). https://doi.org/10.3390/pharmaceutics14091798
  • Pang, H., Wu, H., Zhan, Z., Wu, T., Xiang, M., Wang, Z., Song, L., & Wei, B. (2024). Exploration of anti‑osteosarcoma activity of asiatic acid based on network pharmacology and in vitro experiments. Oncology Reports, 51(2), 1-15.
  • Pantia, S., Kangsamaksin, T., Janvilisri, T., & Komyod, W. (2023). Asiatic acid inhibits nasopharyngeal carcinoma cell viability and migration via suppressing STAT3 and Claudin-1. Pharmaceuticals, 16(6), 902.
  • Pochapski, D. J., Carvalho dos Santos, C., Leite, G. W., Pulcinelli, S. H., & Santilli, C. V. (2021). Zeta Potential and Colloidal Stability Predictions for Inorganic Nanoparticle Dispersions: Effects of Experimental Conditions and Electrokinetic Models on the Interpretation of Results. Langmuir, 37(45), 13379-13389. https://doi.org/10.1021/acs.langmuir.1c02056
  • Qiu, Y., Liu, Y., Wang, L., Xu, L., Bai, R., Ji, Y., Wu, X., Zhao, Y., Li, Y., & Chen, C. (2010). Surface chemistry and aspect ratio mediated cellular uptake of Au nanorods. Biomaterials, 31(30), 7606-7619.
  • Rahman, M. M., Sayeed, M. S. B., Haque, M. A., Hassan, M. M., & Islam, S. (2012). Phytochemical screening, antioxidant, antiAlzheimer and anti-diabetic activities of Centella asiatica. J Nat Prod Plant Resour, 2(4), 504-511.
  • Rai, N., Agrawal, R., & Khan, A. (2014). Centella asiatica extract exhibit anticancer activity against different types of tumours. Int. J. Pure App. Biosci, 2, 122-127.
  • Rauf, S., Hameed, H., Tariq, M., Afareen, A., Gulfaraz, S., AlKubaisi, N. A., & Elshikh, M. S. (2025). Phytochemical‐Mediated Synthesis and Characterization of Silver Nanoparticles Using Mirabilis jalapa Leaf Extract and Their Antibacterial. Microscopy Research and Technique.
  • Razali, N. N. M., Ng, C. T., & Fong, L. Y. (2019). Cardiovascular protective effects of Centella asiatica and its triterpenes: a review. Planta Medica, 85(16), 1203-1215.
  • Rexroth, G., & Scotland, V. (1994). Cardiac toxicity of 5-fluorouracil. Medizinische Klinik (Munich, Germany: 1983), 89(12), 680- 688.
  • Rzayev, Z. M., Tűrk, M., & Söylemez, E. A. (2012). Bioengineering functional copolymers. XXI. Synthesis of a novel end carboxyltrithiocarbonate functionalized poly (maleic anhydride) and its interaction with cancer cells. Bioorganic & Medicinal Chemistry, 20(16), 5053-5061.
  • Sinmez, C. C., Tüfekçi, E., Demir, B. Ş., Eken, A., Guneş, V., Ekici, S., Bozkaya, E., & Aykun, A. İ. (2024). Investigation of immunomodulatory and cytotoxic effects of shed snake skin (Elaphe sauromates) extract. Frontiers in Pharmacology, 15, 1270970.
  • Soyingbe, O. S., Mongalo, N. I., & Makhafola, T. J. (2018). In vitro antibacterial and cytotoxic activity of leaf extracts of Centella asiatica (L.) Urb, Warburgia salutaris (Bertol. F.) Chiov and Curtisia dentata (Burm. F.) C.A.Sm - medicinal plants used in South Africa. BMC Complementary and Alternative Medicine, 18(1), 315. https://doi.org/10.1186/s12906-018-2378-3
  • Şahin, Y., Türk, M., Sevin, S., Peker, K., Bozkaya, E., Peker, S. A., & Çavdar, A. (2023). Cytotoxic and antiproliferative effects of hellebrin on breast and lung cancer cells. Veteriner Hekimler Derneği Dergisi, 94(2), 137-143.
  • Wiciński, M., Fajkiel-Madajczyk, A., Kurant, Z., Gajewska, S., Kurant, D., Kurant, M., & Sousak, M. (2024). Can Asiatic Acid from Centella asiatica Be a Potential Remedy in Cancer Therapy?—A Review. Cancers, 16(7), 1317.
  • Wu, T., Geng, J., Guo, W., Gao, J., & Zhu, X. (2017). Asiatic acid inhibits lung cancer cell growth in vitro and in vivo by destroying mitochondria. Acta Pharm Sin B, 7(1), 65-72. https://doi.org/10.1016/j.apsb.2016.04.003
  • Yırtıcı, Ü., Ergene, A., Adem, Ş., Atalar, M. N., Eyüpoğlu, V., Rawat, R., Arat, E., & Hamzaoğlu, E. (2024). Centaurea mersinensis phytochemical composition and multi-dimensional bioactivity properties supported by molecular modeling. Journal of Biomolecular Structure and Dynamics, 42(5), 2341-2357.
  • Zhang, T., Wang, L., Chen, Q., & Chen, C. (2014). Cytotoxic potential of silver nanoparticles. Yonsei Med J, 55(2), 283-291. https://doi.org/10.3349/ymj.2014.55.2.283
  • Zulkipli, N. N., Zakaria, R., Long, I., Abdullah, S. F., Muhammad, E. F., Wahab, H. A., & Sasongko, T. H. (2020). In silico analyses and cytotoxicity study of asiaticoside and asiatic acid from malaysian plant as potential mTOR inhibitors. Molecules, 25(17), 3991.
There are 59 citations in total.

Details

Primary Language English
Subjects Active Matter Design, Biomaterial , Animal Cell Culture and Tissue Engineering
Journal Section Research Article
Authors

Esra Bozkaya 0000-0002-9259-2538

Early Pub Date November 23, 2025
Publication Date November 30, 2025
Submission Date April 11, 2025
Acceptance Date October 15, 2025
Published in Issue Year 2025 Volume: 17 Issue: 3

Cite

APA Bozkaya, E. (2025). In Vitro Evaluation of the Antineoplastic Activity of Silver Nanoparticles Functionalized with Bioactive Molecules Against SK-MEL-30, MCF-7, and H1299 Cancer Cells. International Journal of Engineering Research and Development, 17(3), 590-603. https://doi.org/10.29137/ijerad.1674277

Kırıkkale University, Faculty of Engineering and Natural Science, 71450 Yahşihan / Kırıkkale, Türkiye.

ijerad@kku.edu.tr