Araştırma Makalesi
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Effect of Electroporation on Antiproliferative Activity of Rheum Ribes and Hypericum Perforatum Extracts in Lung Cancer Cells

Yıl 2025, Cilt: 5 Sayı: 3, 1 - 12, 29.12.2025
https://doi.org/10.71255/maunsbd.1634531
https://izlik.org/JA67UH42FN

Öz

The purpose of this study is to investigate the phenolic substance contents of Hypericum perforatum and Rheum ribes plants and their cytotoxicity on lung cancer cells (A549) and to reveal the effects of electroporation (EP) on the antiproliferative activities of these plants. Antiproliferative activities of plant extracts were determined in A549 cells, and their biocompatibility was evaluated in L-929 fibroblast cells through MTT assay. In electrochemotherapy (extracts+EP) applications of A549 cancer cells, eight square wave electrical pulse sequences with an intensity of 800V/cm were used with various doses of plant extracts. Both plant extracts were observed to be abundant in phenolic compounds and exhibited almost no cytotoxic effects, with IC50 values higher than 1000µg/mL for L-929 fibroblast cells. However, A549 cancer cells showed very good sensitivity to the cytotoxic activities of Rheum ribes and Hypericum perforatum extracts, with IC50 values of 297.32 and 241.10 µg/mL, respectively. The cytotoxic activity of both plant extracts increased considerably with EP, and cell viability percentages of extract+EP groups were observed to decrease significantly compared to extract-only groups (p<0.05). Our findings reveal that Rheum ribes and Hypericum perforatum extracts have anticancer potential and may be promising for lung cancer if used in combination with EP.

Kaynakça

  • Akkol, E. K., Koca, U., Pesin, I., & Yilmazer, D. (2011). Evaluation of the wound healing potential ofAchillea biebersteiniiAfan. (Asteraceae) byin vivoexcision and incision models. Evidence-Based Complementary and Alternative Medicine: eCAM, 2011, 1–7. https://doi.org/10.1093/ecam/nep039
  • Alaca, K., Okumuş, E., Bakkalbaşi, E., & Javidipour, I. (2022). Phytochemicals and antioxidant activities of twelve edible wild plants from Eastern Anatolia, Turkey. Food Science and Technology, 42. https://doi.org/10.1590/fst.18021
  • Alkı̇s, M. E. (2021). Effects of electroporation on cytotoxicity of 4-aminopyrimidin-2-(1H)-one based ligand and its Cobalt (II) and Ruthenium (II) complexes in MCF-7 cancer cells. Dicle Medical Journal / Dicle Tip Dergisi, 48(3), 498–506. https://doi.org/10.5798/dicletip.988061
  • Alkis, M. E., Akdag, M. Z., & Kandemir, S. I. (2022). Influence of extremely low-frequency magnetic field on chemotherapy and electrochemotherapy efficacy in human Caco-2 colon cancer cells. Electromagnetic Biology and Medicine, 41(2), 177–183. https://doi.org/10.1080/15368378.2022.2046047
  • Alkis, M. E., Buldurun, K., Alan, Y., Turan, N., & Altun, A. (2023). Electroporation enhances the anticancer effects of novel Cu(II) and Fe(II) complexes in chemotherapy‐resistant glioblastoma cancer cells. Chemistry & Biodiversity, 20(2). https://doi.org/10.1002/cbdv.202200710
  • Alkış, M. E., Keleştemür, Ü., Alan, Y., Turan, N., & Buldurun, K. (2021a). Cobalt and ruthenium complexes with pyrimidine based schiff base: Synthesis, characterization, anticancer activities and electrochemotherapy efficiency. Journal of Molecular Structure, 1226(129402), 129402. https://doi.org/10.1016/j.molstruc.2020.129402
  • Alkış, M. E., Turan, N., Alan, Y., Irtegun Kandemir, S., & Buldurun, K. (2021b). Effects of electroporation on anticancer activity of 5-FU and newly synthesized zinc(II) complex in chemotherapy-resistance human brain tumor cells. Medical Oncology (Northwood, London, England), 38(11). https://doi.org/10.1007/s12032-021-01579-7 Magda, M. A., and Nehad, M. G. (2011). Antimicrobial efficacy of Rheum palmatum, Curcumalongaand Alpinia officinarumextracts againstsome pathogenic microorganisms. African Journal of Biotechnology, 10, 12058–12063.
  • Azmir, J., Zaidul, I. S. M., Rahman, M. M., Sharif, K. M., Mohamed, A., Sahena, F., Jahurul, M. H. A., Ghafoor, K., Norulaini, N. A. N., & Omar, A. K. M. (2013). Techniques for extraction of bioactive compounds from plant materials: A review. Journal of Food Engineering, 117(4), 426–436. https://doi.org/10.1016/j.jfoodeng.2013.01.014
  • Bade, B. C., & Dela Cruz, C. S. (2020). Lung cancer 2020: Epidemiology, etiology, and prevention. Clinics in Chest Medicine, 41(1), 1–24. https://doi.org/10.1016/j.ccm.2019.10.001
  • Bendix, M. B., Houston, A., Forde, P. F., & Brint, E. (2022). Defining optimal parameters to maximize the effect of electrochemotherapy on lung cancer cells whilst preserving the integrity of immune cells. Bioelectrochemistry (Amsterdam, Netherlands), 148(108257), 108257. https://doi.org/10.1016/j.bioelechem.2022.108257
  • Bruni, R., & Sacchetti, G. (2009). Factors affecting polyphenol biosynthesis in wild and field grown St. John’s Wort (Hypericum perforatum L. Hypericaceae/Guttiferae). Molecules (Basel, Switzerland), 14(2), 682–725. https://doi.org/10.3390/molecules14020682
  • Bute, B., & Alkis, M. E. (2022). Anticancer activity of methotrexate in electrochemotherapy and electrochemotherapy plus ionizing radiation treatments in human breast cancer cells. Medical Oncology (Northwood, London, England), 40(1). https://doi.org/10.1007/s12032-022-01891-w
  • Campana, L. G., Miklavčič, D., Bertino, G., Marconato, R., Valpione, S., Imarisio, I., Dieci, M. V., Granziera, E., Cemazar, M., Alaibac, M., & Sersa, G. (2019). Electrochemotherapy of superficial tumors – Current status: Seminars in Oncology, 46(2), 173–191. https://doi.org/10.1053/j.seminoncol.2019.04.002
  • Chan, W.-J. J., Adiwidjaja, J., McLachlan, A. J., Boddy, A. V., & Harnett, J. E. (2023). Interactions between natural products and cancer treatments: underlying mechanisms and clinical importance. Cancer Chemotherapy and Pharmacology, 91(2), 103–119. https://doi.org/10.1007/s00280-023-04504-z
  • Choromanska, A., Saczko, J., & Kulbacka, J. (2020). Caffeic acid phenethyl ester assisted by reversible electroporation-in vitro study on human melanoma cells. Pharmaceutics, 12(5), 478. https://doi.org/10.3390/pharmaceutics12050478
  • Condello, M., D’Avack, G., Spugnini, E. P., & Meschini, S. (2022). Electrochemotherapy: An alternative strategy for improving therapy in drug-resistant SOLID tumors. Cancers, 14(17), 4341. https://doi.org/10.3390/cancers14174341
  • Crockett, S. L., & Robson, N. K. B. (2011). Taxonomy and chemotaxonomy of the genus Hypericum. Medicinal and Aromatic Plant Science and Biotechnology, 5(Special1), 1–13.
  • Davis, P. H. (1985). Flora of turkey and the east Aegean islands: Vol.8. Edinburgh University Press.
  • Doostmohammadi, A., Jooya, H., Ghorbanian, K., Gohari, S., & Dadashpour, M. (2024). Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents. Cell Communication and Signaling: CCS, 22(1), 228. https://doi.org/10.1186/s12964-024-01607-9
  • Erdoğan, M. K., Agca, C. A., & Geçı̇besler, İ. H. (2020). The antiproliferative potential of isolated emodin and aloe-emodin from Rheum ribes on different cancer cell lines. Biological Diversity and Conservation, 13(2), 160–168. https://doi.org/10.46309/biodicon.2020.753046
  • Esmaeili, N., & Friebe, M. (2019). Electrochemotherapy: A review of current status, alternative IGP approaches, and future perspectives. Journal of Healthcare Engineering, 2019, 1–11. https://doi.org/10.1155/2019/2784516. Fawzi Mahomoodally, M., Zengin, G., Roumita, S.-S., Caprioli, G., Mustafa, A. M., Piatti, D., Yıldıztugay, E., Ak, G.,
  • Esra Karadağ, A., Khalid, A., Abdalla, A. N., Ibrahim Uba, A., & Demirci, F. (2023). Chemical characterization and multidirectional biological effects of different solvent extracts of arum elongatum: In vitro and in silico approaches. Chemistry & Biodiversity, 20(4), e202201181. https://doi.org/10.1002/cbdv.202201181
  • Hasani-Ranjbar, S., Nayebi, N., Moradi, L., Mehri, A., Larijani, B., & Abdollahi, M. (2010). The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Current Pharmaceutical Design, 16(26), 2935–2947. https://doi.org/10.2174/138161210793176464
  • Jeya Shree, T., Gowri Sree, V., Poompavai, S., Sieni, E., Sgarbossa, P., Camarillo, I., & Sundararajan, R. (2022). Inhibition of proliferation of HeLa cells by pulsed electric field treatedMentha piperita(mint) extract. IETE Journal of Research, 68(2), 858–868. https://doi.org/10.1080/03772063.2019.1626295
  • Keser, S., Keser, F., Karatepe, M., Kaygili, O., Tekin, S., Turkoglu, I., Demir, E., Yilmaz, O., Kirbag, S., & Sandal, S. (2020). Bioactive contents, In vitro antiradical, antimicrobial and cytotoxic properties

Elektroporasyonun Akciğer Kanseri Hücrelerinde Rheum Ribes ve Hypericum Perforatum Ekstratlarının Antiproliferatif Aktivitesi Üzerine Etkisi

Yıl 2025, Cilt: 5 Sayı: 3, 1 - 12, 29.12.2025
https://doi.org/10.71255/maunsbd.1634531
https://izlik.org/JA67UH42FN

Öz

Bu çalışmanın amacı, Hypericum perforatum ve Rheum ribes bitkilerinin fenolik madde içeriklerini ve akciğer kanseri hücreleri (A549) üzerindeki sitotoksisitelerini belirlemek ve elektroporasyonun (EP) bu bitkilerin antiproliferatif aktiviteleri üzerindeki etkilerini ortaya koymaktır. Bitki ekstraktlarının antiproliferatif aktiviteleri A549 hücrelerinde, biyouyumlulukları ise L-929 fibroblast hücrelerinde MTT analizi ile test edilmiştir. A549 kanser hücrelerinin elektrokemoterapi (ekstraktlar+EP) uygulamalarında, 800V/cm yoğunluğunda sekiz kare dalga elektriksel puls dizisi, bitki ekstraktlarının çeşitli dozları ile birlikte kullanılmıştır. Her iki bitki ekstraktının da fenolik bileşikler bakımından zengin olduğu ve L-929 fibroblast hücreleri için 1000µg/mL'den daha yüksek IC50 değerleri ile neredeyse hiç sitotoksik etki göstermediği bulunmuştur. Bununla birlikte, A549 kanser hücreleri Rheum ribes ve Hypericum perforatum ekstraktlarının sitotoksik aktivitelerine karşı çok iyi duyarlılık göstermiş ve IC50 değerleri sırasıyla 297,32 ve 241,10 µg/mL olarak bulunmuştur. Her iki bitki ekstraktının sitotoksik aktivitesi EP ile önemli ölçüde artmış ve ekstrakt+EP gruplarının hücre canlılık yüzdelerinin sadece ekstrakt gruplarına kıyasla önemli ölçüde azaldığı görülmüştür (p<0.05). Bulgularımız, Rheum ribes ve Hypericum perforatum ekstraktlarının antikanser potansiyeline sahip olduğunu ve EP ile birlikte kullanıldığında akciğer kanseri için umut verici olabileceğini ortaya koymaktadır.

Kaynakça

  • Akkol, E. K., Koca, U., Pesin, I., & Yilmazer, D. (2011). Evaluation of the wound healing potential ofAchillea biebersteiniiAfan. (Asteraceae) byin vivoexcision and incision models. Evidence-Based Complementary and Alternative Medicine: eCAM, 2011, 1–7. https://doi.org/10.1093/ecam/nep039
  • Alaca, K., Okumuş, E., Bakkalbaşi, E., & Javidipour, I. (2022). Phytochemicals and antioxidant activities of twelve edible wild plants from Eastern Anatolia, Turkey. Food Science and Technology, 42. https://doi.org/10.1590/fst.18021
  • Alkı̇s, M. E. (2021). Effects of electroporation on cytotoxicity of 4-aminopyrimidin-2-(1H)-one based ligand and its Cobalt (II) and Ruthenium (II) complexes in MCF-7 cancer cells. Dicle Medical Journal / Dicle Tip Dergisi, 48(3), 498–506. https://doi.org/10.5798/dicletip.988061
  • Alkis, M. E., Akdag, M. Z., & Kandemir, S. I. (2022). Influence of extremely low-frequency magnetic field on chemotherapy and electrochemotherapy efficacy in human Caco-2 colon cancer cells. Electromagnetic Biology and Medicine, 41(2), 177–183. https://doi.org/10.1080/15368378.2022.2046047
  • Alkis, M. E., Buldurun, K., Alan, Y., Turan, N., & Altun, A. (2023). Electroporation enhances the anticancer effects of novel Cu(II) and Fe(II) complexes in chemotherapy‐resistant glioblastoma cancer cells. Chemistry & Biodiversity, 20(2). https://doi.org/10.1002/cbdv.202200710
  • Alkış, M. E., Keleştemür, Ü., Alan, Y., Turan, N., & Buldurun, K. (2021a). Cobalt and ruthenium complexes with pyrimidine based schiff base: Synthesis, characterization, anticancer activities and electrochemotherapy efficiency. Journal of Molecular Structure, 1226(129402), 129402. https://doi.org/10.1016/j.molstruc.2020.129402
  • Alkış, M. E., Turan, N., Alan, Y., Irtegun Kandemir, S., & Buldurun, K. (2021b). Effects of electroporation on anticancer activity of 5-FU and newly synthesized zinc(II) complex in chemotherapy-resistance human brain tumor cells. Medical Oncology (Northwood, London, England), 38(11). https://doi.org/10.1007/s12032-021-01579-7 Magda, M. A., and Nehad, M. G. (2011). Antimicrobial efficacy of Rheum palmatum, Curcumalongaand Alpinia officinarumextracts againstsome pathogenic microorganisms. African Journal of Biotechnology, 10, 12058–12063.
  • Azmir, J., Zaidul, I. S. M., Rahman, M. M., Sharif, K. M., Mohamed, A., Sahena, F., Jahurul, M. H. A., Ghafoor, K., Norulaini, N. A. N., & Omar, A. K. M. (2013). Techniques for extraction of bioactive compounds from plant materials: A review. Journal of Food Engineering, 117(4), 426–436. https://doi.org/10.1016/j.jfoodeng.2013.01.014
  • Bade, B. C., & Dela Cruz, C. S. (2020). Lung cancer 2020: Epidemiology, etiology, and prevention. Clinics in Chest Medicine, 41(1), 1–24. https://doi.org/10.1016/j.ccm.2019.10.001
  • Bendix, M. B., Houston, A., Forde, P. F., & Brint, E. (2022). Defining optimal parameters to maximize the effect of electrochemotherapy on lung cancer cells whilst preserving the integrity of immune cells. Bioelectrochemistry (Amsterdam, Netherlands), 148(108257), 108257. https://doi.org/10.1016/j.bioelechem.2022.108257
  • Bruni, R., & Sacchetti, G. (2009). Factors affecting polyphenol biosynthesis in wild and field grown St. John’s Wort (Hypericum perforatum L. Hypericaceae/Guttiferae). Molecules (Basel, Switzerland), 14(2), 682–725. https://doi.org/10.3390/molecules14020682
  • Bute, B., & Alkis, M. E. (2022). Anticancer activity of methotrexate in electrochemotherapy and electrochemotherapy plus ionizing radiation treatments in human breast cancer cells. Medical Oncology (Northwood, London, England), 40(1). https://doi.org/10.1007/s12032-022-01891-w
  • Campana, L. G., Miklavčič, D., Bertino, G., Marconato, R., Valpione, S., Imarisio, I., Dieci, M. V., Granziera, E., Cemazar, M., Alaibac, M., & Sersa, G. (2019). Electrochemotherapy of superficial tumors – Current status: Seminars in Oncology, 46(2), 173–191. https://doi.org/10.1053/j.seminoncol.2019.04.002
  • Chan, W.-J. J., Adiwidjaja, J., McLachlan, A. J., Boddy, A. V., & Harnett, J. E. (2023). Interactions between natural products and cancer treatments: underlying mechanisms and clinical importance. Cancer Chemotherapy and Pharmacology, 91(2), 103–119. https://doi.org/10.1007/s00280-023-04504-z
  • Choromanska, A., Saczko, J., & Kulbacka, J. (2020). Caffeic acid phenethyl ester assisted by reversible electroporation-in vitro study on human melanoma cells. Pharmaceutics, 12(5), 478. https://doi.org/10.3390/pharmaceutics12050478
  • Condello, M., D’Avack, G., Spugnini, E. P., & Meschini, S. (2022). Electrochemotherapy: An alternative strategy for improving therapy in drug-resistant SOLID tumors. Cancers, 14(17), 4341. https://doi.org/10.3390/cancers14174341
  • Crockett, S. L., & Robson, N. K. B. (2011). Taxonomy and chemotaxonomy of the genus Hypericum. Medicinal and Aromatic Plant Science and Biotechnology, 5(Special1), 1–13.
  • Davis, P. H. (1985). Flora of turkey and the east Aegean islands: Vol.8. Edinburgh University Press.
  • Doostmohammadi, A., Jooya, H., Ghorbanian, K., Gohari, S., & Dadashpour, M. (2024). Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents. Cell Communication and Signaling: CCS, 22(1), 228. https://doi.org/10.1186/s12964-024-01607-9
  • Erdoğan, M. K., Agca, C. A., & Geçı̇besler, İ. H. (2020). The antiproliferative potential of isolated emodin and aloe-emodin from Rheum ribes on different cancer cell lines. Biological Diversity and Conservation, 13(2), 160–168. https://doi.org/10.46309/biodicon.2020.753046
  • Esmaeili, N., & Friebe, M. (2019). Electrochemotherapy: A review of current status, alternative IGP approaches, and future perspectives. Journal of Healthcare Engineering, 2019, 1–11. https://doi.org/10.1155/2019/2784516. Fawzi Mahomoodally, M., Zengin, G., Roumita, S.-S., Caprioli, G., Mustafa, A. M., Piatti, D., Yıldıztugay, E., Ak, G.,
  • Esra Karadağ, A., Khalid, A., Abdalla, A. N., Ibrahim Uba, A., & Demirci, F. (2023). Chemical characterization and multidirectional biological effects of different solvent extracts of arum elongatum: In vitro and in silico approaches. Chemistry & Biodiversity, 20(4), e202201181. https://doi.org/10.1002/cbdv.202201181
  • Hasani-Ranjbar, S., Nayebi, N., Moradi, L., Mehri, A., Larijani, B., & Abdollahi, M. (2010). The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Current Pharmaceutical Design, 16(26), 2935–2947. https://doi.org/10.2174/138161210793176464
  • Jeya Shree, T., Gowri Sree, V., Poompavai, S., Sieni, E., Sgarbossa, P., Camarillo, I., & Sundararajan, R. (2022). Inhibition of proliferation of HeLa cells by pulsed electric field treatedMentha piperita(mint) extract. IETE Journal of Research, 68(2), 858–868. https://doi.org/10.1080/03772063.2019.1626295
  • Keser, S., Keser, F., Karatepe, M., Kaygili, O., Tekin, S., Turkoglu, I., Demir, E., Yilmaz, O., Kirbag, S., & Sandal, S. (2020). Bioactive contents, In vitro antiradical, antimicrobial and cytotoxic properties
Toplam 25 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Farmasotik Biyoteknoloji, Farmasotik Botanik, Kemoterapi
Bölüm Araştırma Makalesi
Yazarlar

Mehmet Eşref Alkış 0000-0002-3321-2873

Fuat Yetişsin 0000-0001-6085-7610

Gönderilme Tarihi 6 Şubat 2025
Kabul Tarihi 21 Temmuz 2025
Yayımlanma Tarihi 29 Aralık 2025
DOI https://doi.org/10.71255/maunsbd.1634531
IZ https://izlik.org/JA67UH42FN
Yayımlandığı Sayı Yıl 2025 Cilt: 5 Sayı: 3

Kaynak Göster

APA Alkış, M. E., & Yetişsin, F. (2025). Effect of Electroporation on Antiproliferative Activity of Rheum Ribes and Hypericum Perforatum Extracts in Lung Cancer Cells. Muş Alparslan Üniversitesi Sağlık Bilimleri Dergisi, 5(3), 1-12. https://doi.org/10.71255/maunsbd.1634531