Publicado

2026-09-11

Cell line–dependent cytotoxicity and selective phenolic handling of Lamium spp. extracts in human cancer cell models

Citotoxicidad dependiente de la línea celular y manejo selectivo de compuestos fenólicos de extractos de Lamium spp. en modelos de células cancerosas humanas

Citotoxicidade dependente da linhagem celular e manipulação seletiva de compostos fenólicos de extratos de Lamium spp. em modelos de células cancerígenas humanas

DOI:

https://doi.org/10.15446/rcciquifa.v55n3.127104

Palabras clave:

Lamium spp, cytotoxicity, phenolic compounds (en)
Lamium spp, citotoxicidad, compuestos fenólicos (es)
Lamium spp., citotoxicidad, compuestos fenólicos (pt)

Descargas

Autores/as

  • Viktoryia Tsiarletskaya Department of Pharmaceutical Chemistry with Course of Advanced Training and Retraining, Faculty of Pharmacy, Belarusian State Medical University, 220083, Republic of Belarus, Minsk https://orcid.org/0009-0000-8848-4617
  • Raman Lukahou Department of Pharmaceutical Chemistry with Course of Advanced Training and Retraining, Faculty of Pharmacy, Belarusian State Medical University
  • Nadezhda Bobrova Republican Molecular-Genetic Laboratory of Carcinogenesis, N. N. Alexandrov National Cancer Centre of Belarus, 223040, Republic of Belarus
  • Ihar Seviaryn Republican Molecular-Genetic Laboratory of Carcinogenesis, N. N. Alexandrov National Cancer Centre of Belarus, 223040, Republic of Belarus
  • Tatiana Doroshenko Republican Molecular-Genetic Laboratory of Carcinogenesis, N. N. Alexandrov National Cancer Centre of Belarus, 223040, Republic of Belarus
  • Anna Portyanko Republican Molecular-Genetic Laboratory of Carcinogenesis, N. N. Alexandrov National Cancer Centre of Belarus, 223040, Republic of Belarus

Introduction: Plant extracts are widely investigated as sources of cytostatic bioactive compounds. Previous studies have reported cytotoxic activity of several Lamium species in vitro. However, comparative data across species and cell lines remain scarce, and the role of phenolic compounds in this activity is still poorly understood. Objective: Hydroalcoholic extracts of L. album, L. purpureum, L. maculatum, and L. galeobdolon were tested against A549 (lung adenocarcinoma), BJ-hTERT (immortalized human foreskin fibroblasts), HeLa (human cervical carcinoma), HROG04 (human glioblastoma), MeWo (human melanoma), NIH:OVCAR-3 (human ovarian adenocarcinoma), PC-3 (prostate adenocarcinoma), ZR-75 (human breast adenocarcinoma) cell lines. Methodology: Cytotoxic activity was evaluated using the MTT assay, and changes in phenolic composition were analyzed by HPLC-DAD. Results: all investigated extracts exhibited the lowest IC₅₀ values against NIH:OVCAR-3, HROG04, and ZR-75 cells (<375 µg/mL), with a selectivity index relative to BJ-hTERT cells exceeding 4 for all extracts. HPLC-DAD revealed changes in extracellular phenolic concentrations, including the appearance of new peaks and the disappearance of others. BJ-hTERT cells showed less marked alterations in the medium composition. Conclusion: Lamium spp. extracts exhibit selective cytotoxicity toward specific cancer cell lines, possibly associated with dynamic changes in extracellular phenolic compounds.

 

Introducción: Los extractos vegetales son ampliamente estudiados como fuentes de compuestos bioactivos con actividad citostática. Estudios previos han reportado actividad citotóxica de varias especies del género Lamium in vitro; sin embargo, los datos comparativos entre especies y líneas celulares siguen siendo escasos, y el papel de los compuestos fenólicos en esta actividad aún no está completamente esclarecido. Objetivo: Se evaluaron extractos hidroalcohólicos de L. album, L. purpureum, L. maculatum y L. galeobdolon frente a las líneas celulares A549 (adenocarcinoma pulmonar), BJ-hTERT (fibroblastos humanos de prepucio inmortalizados), HeLa (carcinoma cervical humano), HROG04 (glioblastoma humano), MeWo (melanoma humano), NIH:OVCAR-3 (adenocarcinoma ovárico humano), PC-3 (adenocarcinoma prostático) y ZR-75 (adenocarcinoma mamario humano). Metodología: La actividad citotóxica se evaluó mediante el ensayo MTT, y los cambios en la composición fenólica se analizaron mediante HPLC-DAD. Resultados: Todos los extractos investigados presentaron los valores más bajos de IC₅₀ en las líneas NIH:OVCAR-3, HROG04 y ZR-75 (<375 µg/mL), con un índice de selectividad superior a 4 respecto a las células BJ-hTERT. El análisis mediante HPLC-DAD reveló cambios en las concentraciones de compuestos fenólicos extracelulares, incluyendo la aparición de nuevos picos y la desaparición de otros. En las células BJ-hTERT se observaron alteraciones menos marcadas en la composición del medio. Conclusión: Los extractos de Lamium spp. presentan citotoxicidad selectiva frente a determinadas líneas celulares cancerosas, posiblemente asociada a cambios dinámicos en los compuestos fenólicos extracelulares.

Introdução: Extratos de plantas são amplamente investigados como fontes de compostos bioativos citostáticos. Estudos anteriores relataram atividade citotóxica de diversas espécies de Lamium in vitro. No entanto, dados comparativos entre espécies e linhagens celulares ainda são escassos, e o papel dos compostos fenólicos nessa atividade ainda é pouco compreendido. Objetivo: Extratos hidroalcoólicos de L. album, L. purpureum, L. maculatum e L. galeobdolon foram testados contra as linhagens celulares A549 (adenocarcinoma de pulmão), BJ-hTERT (fibroblastos imortalizados de prepúcio humano), HeLa (carcinoma cervical humano), HROG04 (glioblastoma humano), MeWo (melanoma humano), NIH:OVCAR-3 (adenocarcinoma ovariano humano), PC-3 (adenocarcinoma de próstata) e ZR-75 (adenocarcinoma de mama humano). Metodologia: A atividade citotóxica foi avaliada pelo ensaio MTT e as alterações na composição fenólica foram analisadas por HPLC-DAD. Resultados: todos os extratos investigados apresentaram os menores valores de IC₅₀ contra as células NIH:OVCAR-3, HROG04 e ZR-75 (<375 µg/mL), com um índice de seletividade em relação às células BJ-hTERT superior a 4 para todos os extratos. A HPLC-DAD revelou alterações nas concentrações de fenólicos extracelulares, incluindo o aparecimento de novos picos e o desaparecimento de outros. As células BJ-hTERT apresentaram alterações menos acentuadas na composição do meio. Conclusão: Os extratos de Lamium spp. exibem citotoxicidade seletiva contra linhagens celulares cancerígenas específicas, possivelmente associada a alterações dinâmicas nos compostos fenólicos extracelulares.

Referencias

1. F. Bray, M. Laversanne, H. Sung, J. Ferlay, R.L. Siegel, I. Soerjomataram & A. Jemal. Global can-cer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 74(3), 229–263 (2024). https://doi.org/10.3322/ caac.21834

2. N. Muniraj, S. Siddharth & D. Sharma. Bioactive compounds: multi-targeting silver bullets for preventing and treating breast cancer. Cancers, 11(10), 1563 (2019). https://doi.org/10.3390/cancers11101563

3. A.M.L. Seca & D.C.G.A. Pinto. Plant secondary metabolites as anticancer agents: successes in clinical trials and therapeutic application. International Journal of Molecular Sciences, 19(1), 263 (2018). https://doi.org/10.3390/ijms19010263

4. C.A. Dehelean, I. Marcovici, C. Soica, M. Mioc, D. Coricovac, S. Iurciuc, O.M. Cretu & I. Pinza-ru. Plant-derived anticancer compounds as new perspectives in drug discovery and alternative therapy. Molecules, 26(4), 1109 (2021). https://doi.org/10.3390/molecules26041109

5. T. Saghatelyan, A. Tananyan, N. Janoyan, A. Tadevosyan, H. Petrosyan, A. Hovhannisyan, et al. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial. Phytomedicine, 70, 153218 (2020). https://doi.org/10.1016/j.phymed.2020.153218

6. R.N. Senguttuvan, H. Cho, X. Wu, P.H. Frankel, N. Ruel, S.E. Yost, et al. The anti-cancer role of pterostilbene in endometrial cancer: a phase II prospective, randomized, window-of-opportunity clinical trial with megestrol acetate. Antioxidants, 14(3), 345 (2025). https://doi.org/10.3390/antiox14030345

7. G.S. Kienle, A. Glockmann, M. Schink & H. Kiene. Viscum album L. extracts in breast and gynae-cological cancers: a systematic review of clinical and preclinical research. Journal of Experi-mental & Clinical Cancer Research, 28(1), 79 (2009). https://doi.org/10.1186/1756-9966-28-79

8. İ. Atlıhan, A. Güner, F.Ş. Aslan, A. Şen, O. Orun & P.M. Tiber. Antiproliferative and apoptotic effects of Lamium purpureum L. extract on prostate cancer cells: Lamium purpureum effect on prostate cancer. Indian Journal of Experimental Biology, 63(2), 142–148 (2025). https://doi.org/10.56042/ ijeb.v63i02.13811

9. V. Moskova-Doumanova, G. Miteva, M. Dimitrova, T. Topouzova-Hristova & V. Kapchina. Methanol and chloroform extracts from Lamium album L. affect cell properties of A549 cancer lung cell line. Biotechnology & Biotechnological Equipment, 26(sup1), 120–125 (2012). https://doi.org/10.5504/ 50yrtimb.2011.0022

10. A. Ghalkhani, S. Moradkhani, M. Soleimani & D. Dastan. Functional components, antibacterial, antioxidant, and cytotoxic activities of Lamium garganicum L. ssp. pictum as a novel natural agents from Lamiaceae family. Food Bioscience, 43, 101265 (2021). https://doi.org/10.1016/j.fbio.2021.101265

11. Z.P. Yordanova, M.K. Zhiponova, E.T. Iakimova, M.A. Dimitrova & V.M. Kapchina-Toteva. Revealing the reviving secret of the white dead nettle (Lamium album L.). Phytochemistry Re-views, 13, 375–389 (2014). https://doi.org/10.1007/s11101-014-9356-2

12. N. Ganot, S. Meker, L. Reytman, A. Tzubery & E.Y. Tshuva. Anticancer metal complexes: syn-thesis and cytotoxicity evaluation by the MTT assay. Journal of Visualized Experiments, 81, e50767 (2013). https://doi.org/10.3791/50767

13. L. Tolosa, M.T. Donato & M.J. Gómez-Lechón. General cytotoxicity assessment by means of the MTT assay. In: M. Vinken & V. Rogiers (editors). Protocols in In Vitro Hepatocyte Research. Meth-ods in Molecular Biology, 1250, Springer, 2015; pp. 333–348. https://doi.org/10.1007/978-1-4939-2074-7_26

14. M. Ghasemi, T. Turnbull, S. Sebastian & I. Kempson. The MTT Assay: utility, limitations, pit-falls, and interpretation in bulk and single-cell analysis. International Journal of Molecular Sci-ences, 22(23), 12827 (2021). https://doi.org/10.3390/ijms222312827

15. V.A. Tsiarletskaya & R.I. Lukashou. Razrabotka parametrov ekstraktsii summy fenolnykh soedinenii, verbaskozida i kisloty khlorogenovoi iz rastenii roda Lamium, proizrastayushchikh v Respublike Belarus [Development of extraction parameters of phenolic compounds, verbas-coside and chlorogenic acid from plants of the genus Lamium growing in the Republic of Bela-rus]. Vestnik Farmacii, 3(109), 10–23 (2025). https://doi.org/10.52540/2074-9457.2025.3.10

16. M.E. Czerwińska, E. Kalinowska, D. Popowski & A. Bazylko. Lamalbid, chlorogenic acid, and verbascoside as tools for standardization of Lamium album flowers—development and valida-tion of HPLC–DAD method. Molecules, 25(7), 1721 (2020). https://doi.org/10.3390/molecules25071721

17. T. Mosmann. Rapid colorimetric assay for cellular growth and survival: application to prolif-eration and cytotoxicity assays. Journal of Immunological Methods, 65(1-2), 55–63 (1983). https://doi.org/10.1016/0022-1759(83)90303-4

18. M. de Oliveira, C. Bezerra da Silva, B.C. Konopatzki-Hirota, C. Freitas de Oliveira, K.S. Rech, C. da Silva-Paula, J.d.F. Gaspari-Dias, O. Gomes-Miguel, C. Garcia-Auer & M. Dallarmi-Miguel. Botrytis cinerea: acetylcholinesterase inhibition, cytotoxicity, antimicrobial, larvicidal activity and metabolite isolated from fungal extract. Brazilian Journal of Pharmaceutical Sciences, 60, e23702 (2024). https://doi.org/10.1590/s2175-97902024e23702

19. W. Mahavorasirikul, V. Viyanant, W. Chaijaroenkul, A. Itharat & N. Na-Bangchang. Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepato-carcinoma cells in vitro. BMC Complementary Medicine and Therapies, 10, 55 (2010). https://doi.org/10.1186/1472-6882-10-55

20. L.M. Nogueira de Oliveira, M.d.S. Rocha-Bastos, A.C. Silva de Lima, E.A. Teixera de Figueiredo, F.G. Braga-Dias, L. Morais-Ribeiro da Silva, S.D. Benevides, P.R. Vasconcelos-Ribeiro, L.B.d. Sousa-Sabino & R. Wilane de Figueiredo. Chemical characterization, cytotoxicity, antimicrobi-al and antioxidant potential of Justicia pectoralis Jacq and Croton jacobinensis Baill extracts. Bra-zilian Journal of Pharmaceutical Sciences, 59, e21224 (2023). https://doi.org/10.1590/s2175-97902023e21224

21. M. Leri, M. Scuto, M.L. Ontario, V. Calabrese, J. Edward, E.J. Calabrese, M. Bucciantini & M. Stefani. Healthy effects of plant polyphenols: molecular mechanisms. International Journal of Molecular Sciences, 21(4), 1250 (2020). https://doi.org/10.3390/ijms21041250

22. D. Karakaş, F. Ari & E. Ulukaya. The MTT viability assay yields strikingly false-positive viabili-ties although the cells are killed by some plant extracts. Turkish Journal of Biology, 41(6), 919–925 (2017). https://doi.org/10.3906/biy-1703-104

23. J. Peragón, E. Rufino-Palomares, I. Muñoz-Espada, F. Reyes-Zurita & J.A. Lupiáñez. A new HPLC-MS method for measuring maslinic acid and oleanolic acid in HT29 and HepG2 Human Cancer Cells. International Journal of Molecular Sciences, 16(9), 21681–21694 (2015). https://doi.org/10.3390/ ijms160921681

24. T. Srisongkram & N. Weerapreeyakul. Validation of cell-based assay for quantification of ses-amol uptake and its application for measuring target exposure. Molecules, 24(19), 3522 (2019). https://doi.org/10.3390/molecules24193522

25. W. Yulianto, N. Andarwulan, P.E. Giriwono & J. Pamungkas. HPLC-based metabolomics to identify cytotoxic compounds from Plectranthus amboinicus (Lour.) Spreng against human breast cancer MCF-7 cells. Journal of Chromatography B, 1039, 28–34 (2016). https://doi.org/10.1016/j.jchromb. 2016.10.024

26. F. Moradi-Afrapoli, M. Shokrzadeh, F. Barzegar, G. Gorji-Bahri, R. Zadali & S.N. Ebrahimi. Cytotoxic activity of abietane diterpenoids from roots of Salvia sahendica by HPLC-based activ-ity profiling. Revista Brasileira de Farmacognosia, 28(1), 27–33 (2018). https://doi.org/10.1016/j.bjp.2017. 11.007

27. V.A. Tsiarletskaya & R.I. Lukashou. Sravnitelnyi analiz komponentnogo sostava rastenii roda Lamium metodom vysokoeffektivnoi zhidkostnoi khromatografii [Comparative analysis of the component composition of plants of the genus Lamium by high-performance liquid chromatog-raphy]. Vestnik Farmacii, 4(106), 55–63 (2024). https://doi.org/10.52540/2074-9457.2024.4.55

28. K. Alipieva, L. Korkina, I.E. Orhan & M.I. Georgiev. Verbascoside — A review of its occurrence, (bio)synthesis and pharmacological significance. Biotechnology Advances, 32(6), 1065–1076 (2014). https://doi.org/10.1016/j.biotechadv.2014.07.001

29. M. Marčetić, B. Bufan, M. Drobac, J.A. Stanković, N.A. Ranin, M.T. Milenković & D.D. Božić. Multifaceted biological properties of verbascoside/acteoside: antimicrobial, cytotoxic, anti-inflammatory, and immunomodulatory effects. Antibiotics, 14(7), 697 (2025). https://doi.org/10.3390/antibiotics14070697

30. N. Cortez, C. Villegas, V. Burgos, L. Ortiz, J.R. Cabrera-Pardo & C. Paz. Therapeutic potential of chlorogenic acid in chemoresistance and chemoprotection in cancer treatment. International Journal of Molecular Sciences, 25(10), 5189 (2024). https://doi.org/10.3390/ijms25105189

31. B. Salehi, L. Armstrong, A. Rescigno, B. Yeskaliyeva, G. Seitimova, A. Beyatli, et al. Lamium plants—a comprehensive review on health benefits and biological activities. Molecules, 24(10), 1913 (2019). https://doi.org/10.3390/molecules24101913

32. T. Ndongwe, B.A. Witika, N.P. Mncwangi, M.S. Poka, P.P. Skosana, P.H. Demana, B. Summers & X. Siwe-Noundou. Iridoid derivatives as anticancer agents: an updated review from 1970–2022. Cancers, 15(3), 770 (2023). https://doi.org/10.3390/cancers15030770

33. G.-Y. Liou & P. Storz. Reactive oxygen species in cancer. Free Radical Research, 44(5), 479–496 (2010). https://doi.org/10.3109/10715761003667554

34. R. Veleva, B. Petkova, V. Moskova-Doumanova, J. Doumanov, M. Dimitrova, P. Koleva, K. Mladenova, S. Petrova, Z. Yordanova, V. Kapchina-Toteva & T. Topouzova-Hristova. Changes in the functional characteristics of tumor and normal cells after treatment with extracts of white dead-nettle. Biotechnology & Biotechnological Equipment, 29(1), 181–188 (2015). https://doi.org/10.1080/ 13102818.2014.989094

35. M. Cipolletti, V. Solar-Fernandez, E. Montalesi, M. Marino & M. Fiocchetti. Beyond the antioxi-dant activity of dietary polyphenols in cancer: the modulation of estrogen receptors (ERs) sig-naling. International Journal of Molecular Sciences, 19(9), 2624 (2018). https://doi.org/10.3390/ijms19092624

36. S. Poschner, A. Maier-Salamon, T. Thalhammer & W. Jäger. Resveratrol and other dietary pol-yphenols are inhibitors of estrogen metabolism in human breast cancer cells. The Journal of Steroid Biochemistry and Molecular Biology, 190, 11–18 (2019). https://doi.org/10.1016/j.jsbmb.2019.03.001

37. M. He, L. Xia & J. Li. Potential mechanisms of plant-derived natural products in the treatment of cervical cancer. Biomolecules, 11(10), 1539 (2021). https://doi.org/10.3390/biom11101539

38. S. An, J. An, D. Lee, H.N. Kang, S. Kang, C.-H. Ahn, R.A. Syahputra, R.I.M.A. Ribeiro & B. Kim. Natural products for melanoma therapy: from traditional medicine to modern drug discovery. Plants, 14(6), 951 (2025). https://doi.org/10.3390/plants14060951

Dimensions

PlumX

Visitas a la página del resumen del artículo

117

Descargas

Los datos de descarga aún no están disponibles.

Cómo citar

Tsiarletskaya, V., Lukahou, R., Bobrova, N. ., Seviaryn, I., Doroshenko, T., & Portyanko, A. (2026). Citotoxicidad dependiente de la línea celular y manejo selectivo de compuestos fenólicos de extractos de Lamium spp. en modelos de células cancerosas humanas. Revista Colombiana De Ciencias Químico-Farmacéuticas, 55(3), 977-996. https://doi.org/10.15446/rcciquifa.v55n3.127104

Licencia

Derechos de autor 2026 Revista Colombiana de Ciencias Químico-Farmacéuticas

Creative Commons License

Esta obra está bajo una licencia internacional Creative Commons Atribución 4.0.

El Departamento de Farmacia de la Facultad de Ciencias de la Universidad Nacional de Colombia  autoriza la fotocopia de artículos y textos para fines de uso académico o interno de las instituciones citando la fuente. Las ideas emitidas por los autores son responsabilidad expresa de estos y no de la revista.

Todo el contenido de esta revista, excepto dónde está identificado, está bajo una Licencia Creative Commons de Atribución 4.0 aprobada en Colombia. Consulte la normativa en: http://co.creativecommons.org/?page_id=13