Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts
The present study evaluates the cytotoxicity of a previously synthesized conjugate of betulinic acid (BA) with the penetrating cation F16 on breast adenocarcinoma (MCF-7) and human fibroblast (HF) cell lines, and also shows the mechanism underlying its membranotropic action. It was confirmed that th...
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MDPI AG
2022-11-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/10/11/2903 |
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| author | Konstantin N. Belosludtsev Anna I. Ilzorkina Natalia V. Belosludtseva Vyacheslav A. Sharapov Nikita V. Penkov Dmitriy A. Serov Maxim N. Karagyaur Darya A. Nedopekina Eldar V. Davletshin Marina E. Solovieva Anna Yu Spivak Ulyana Sh. Kuzmina Yulia V. Vakhitova Vladimir S. Akatov Mikhail V. Dubinin |
| author_facet | Konstantin N. Belosludtsev Anna I. Ilzorkina Natalia V. Belosludtseva Vyacheslav A. Sharapov Nikita V. Penkov Dmitriy A. Serov Maxim N. Karagyaur Darya A. Nedopekina Eldar V. Davletshin Marina E. Solovieva Anna Yu Spivak Ulyana Sh. Kuzmina Yulia V. Vakhitova Vladimir S. Akatov Mikhail V. Dubinin |
| author_sort | Konstantin N. Belosludtsev |
| collection | DOAJ |
| description | The present study evaluates the cytotoxicity of a previously synthesized conjugate of betulinic acid (BA) with the penetrating cation F16 on breast adenocarcinoma (MCF-7) and human fibroblast (HF) cell lines, and also shows the mechanism underlying its membranotropic action. It was confirmed that the conjugate exhibits higher cytotoxicity compared to native BA at low doses also blocking the proliferation of both cell lines and causing cell cycle arrest in the G<sub>0</sub>/G<sub>1</sub> phase. We show that the conjugate indeed has a high potential for accumulation in mitochondria, being visualized in these organelles, which is most pronounced in cancer cells. The effect of the conjugate was observed to be accompanied by ROS hyperproduction in both cancerous and healthy cells, despite the lower base level of ROS in the latter. Along with this, using artificial liposomes, we determined that the conjugate is able to influence the phase state of lipid membranes, make them more fluid, and induce nonspecific permeabilization contributing to the overall cytotoxicity of the tested agent. We conclude that the studied BA–F16 conjugate does not have significant selective cytotoxicity, at least against the studied breast cancer cell line MCF-7. |
| first_indexed | 2024-03-09T18:27:49Z |
| format | Article |
| id | doaj.art-d8db71920aa640569f976a059a164c58 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T18:27:49Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-d8db71920aa640569f976a059a164c582023-11-24T07:45:56ZengMDPI AGBiomedicines2227-90592022-11-011011290310.3390/biomedicines10112903Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human FibroblastsKonstantin N. Belosludtsev0Anna I. Ilzorkina1Natalia V. Belosludtseva2Vyacheslav A. Sharapov3Nikita V. Penkov4Dmitriy A. Serov5Maxim N. Karagyaur6Darya A. Nedopekina7Eldar V. Davletshin8Marina E. Solovieva9Anna Yu Spivak10Ulyana Sh. Kuzmina11Yulia V. Vakhitova12Vladimir S. Akatov13Mikhail V. Dubinin14Department of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, RussiaInstitute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, RussiaDepartment of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, RussiaDepartment of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, RussiaFederal Research Center, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Institute of Cell Biophysics of the Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, RussiaFederal Research Center, Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, Institute of Cell Biophysics of the Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, RussiaInstitute for Regenerative Medicine, Medical Research and Education Center, Lomonosov Moscow State University, 27/10, Lomonosovsky Ave., 119192 Moscow, RussiaInstitute of Petrochemistry and Catalysis, Ufa Federal Research Center, Russian Academy of Sciences, Prospekt Oktyabrya 141, 450075 Ufa, RussiaInstitute of Petrochemistry and Catalysis, Ufa Federal Research Center, Russian Academy of Sciences, Prospekt Oktyabrya 141, 450075 Ufa, RussiaInstitute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, RussiaInstitute of Petrochemistry and Catalysis, Ufa Federal Research Center, Russian Academy of Sciences, Prospekt Oktyabrya 141, 450075 Ufa, RussiaInstitute of Biochemistry and Genetics, Ufa Federal Research Center, Russian Academy of Sciences, Prospekt Oktyabrya 71, 450054 Ufa, RussiaInstitute of Biochemistry and Genetics, Ufa Federal Research Center, Russian Academy of Sciences, Prospekt Oktyabrya 71, 450054 Ufa, RussiaInstitute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Institutskaya 3, 142290 Pushchino, RussiaDepartment of Biochemistry, Cell Biology and Microbiology, Mari State University, pl. Lenina 1, 424001 Yoshkar-Ola, RussiaThe present study evaluates the cytotoxicity of a previously synthesized conjugate of betulinic acid (BA) with the penetrating cation F16 on breast adenocarcinoma (MCF-7) and human fibroblast (HF) cell lines, and also shows the mechanism underlying its membranotropic action. It was confirmed that the conjugate exhibits higher cytotoxicity compared to native BA at low doses also blocking the proliferation of both cell lines and causing cell cycle arrest in the G<sub>0</sub>/G<sub>1</sub> phase. We show that the conjugate indeed has a high potential for accumulation in mitochondria, being visualized in these organelles, which is most pronounced in cancer cells. The effect of the conjugate was observed to be accompanied by ROS hyperproduction in both cancerous and healthy cells, despite the lower base level of ROS in the latter. Along with this, using artificial liposomes, we determined that the conjugate is able to influence the phase state of lipid membranes, make them more fluid, and induce nonspecific permeabilization contributing to the overall cytotoxicity of the tested agent. We conclude that the studied BA–F16 conjugate does not have significant selective cytotoxicity, at least against the studied breast cancer cell line MCF-7.https://www.mdpi.com/2227-9059/10/11/2903F16delocalized lipophilic cation (DLC)BAoxidative stresscytotoxicitybreast cancer |
| spellingShingle | Konstantin N. Belosludtsev Anna I. Ilzorkina Natalia V. Belosludtseva Vyacheslav A. Sharapov Nikita V. Penkov Dmitriy A. Serov Maxim N. Karagyaur Darya A. Nedopekina Eldar V. Davletshin Marina E. Solovieva Anna Yu Spivak Ulyana Sh. Kuzmina Yulia V. Vakhitova Vladimir S. Akatov Mikhail V. Dubinin Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts Biomedicines F16 delocalized lipophilic cation (DLC) BA oxidative stress cytotoxicity breast cancer |
| title | Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts |
| title_full | Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts |
| title_fullStr | Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts |
| title_full_unstemmed | Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts |
| title_short | Comparative Study of Cytotoxic and Membranotropic Properties of Betulinic Acid-F16 Conjugate on Breast Adenocarcinoma Cells (MCF-7) and Primary Human Fibroblasts |
| title_sort | comparative study of cytotoxic and membranotropic properties of betulinic acid f16 conjugate on breast adenocarcinoma cells mcf 7 and primary human fibroblasts |
| topic | F16 delocalized lipophilic cation (DLC) BA oxidative stress cytotoxicity breast cancer |
| url | https://www.mdpi.com/2227-9059/10/11/2903 |
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