Antiproliferative properties of a new plant alkaloid against cellular colorectal cancer cultures
https://doi.org/10.37748/2686-9039-2025-6-4-2
EDN: PHKINR
Abstract
Purpose of the study. To evaluate the antiproliferative properties of the novel alkaloid (P1) against CRC cell lines HT‑29, Caco‑2, and HCT116.
Materials and methods. CRC cell lines (HCT116, HT‑29, Caco‑2) were used in the experiments. The alkaloid (P1) was isolated from Petasites hybridus (L.) G. Gaertn., B. Mey. & Scherb and identified using high-performance liquid chromatography (HPLC) and nuclear magnetic resonance spectroscopy (NMR). Cells were incubated with various concentrations of the alkaloid, and cell viability was assessed. Berberine, a well-known anticancer alkaloid, served as the reference compound.
Results. The alkaloid (P1) demonstrated pronounced antiproliferative activity across all tested colorectal cancer cell lines – HCT116, HT‑29, and Caco‑2. The highest sensitivity was observed in HCT116 cells, with an IC50 value of 15.73 μmol/L after 72‑hour incubation, indicating a substantial inhibitory effect on tumor cell proliferation. Comparative analysis showed that (P1) exhibited greater cytostatic efficacy than berberine in Caco‑2 (IC50 (P1) = 54.489 ± 8.3 μmol/L vs IC50 (berb) = 193.154 ± 13.1 μmol/L) and HT‑29 cultures (IC50 (P1) = 55.375 ± 7.1 μmol/L vs IC50 (berb) = 90.22 ± 8.2 μmol/L).
Conclusion. The findings indicate that the alkaloid (P1) possesses significant antiproliferative potential against colorectal cancer cell lines, underscoring its promise as a prospective anticancer agent. Notably, its superior efficacy compared with berberine highlights the relevance of further investigation. These results support continued development of (P1) as a basis for novel therapeutic agents. Future work should include detailed preclinical and clinical studies to elucidate its mechanism of action, evaluate safety and in vivo efficacy, and optimize pharmacological properties for potential clinical application.
About the Authors
S. V. TimofeevaNational Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Sofia V. Timofeeva – Researcher, Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-5945-5961, eLibrary SPIN: 5362-1915, AuthorID: 1064599, Scopus Author ID: 57243356500
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
S. Yu. Filippova
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Svetlana Yu. Filippova – Researcher, Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-4558-5896, eLibrary SPIN: 9586-2785, AuthorID: 878784, Scopus Author ID: 57189618843
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
T. V. Chembarova
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Tatiana V. Chembarova – Junior Researcher of Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-4555-8556, eLibrary SPIN: 5426-1873, AuthorID: 1051985, Scopus Author ID: 57221303597
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
N. V. Gnennaya
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Nadezhda V. Gnennaya – Junior Researcher of Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-3691-3317, eLibrary SPIN: 9244-2318, AuthorID: 900758, Scopus Author ID: 57214806863
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
I. V. Mezhevova
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Irina V. Mezhevova – Junior Researcher of Laboratory of Cell Technologies, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-7902-7278, eLibrary SPIN: 3367-1741, AuthorID: 1011695, Scopus Author ID: 57296602900
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
E. Yu. Zlatnik
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Elena Yu. Zlatnik – Dr. Sci. (Medicine), Professor, Leading Researcher, Laboratory of Immunophenotyping, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-1410-122X, eLibrary SPIN: 4137-7410, AuthorID: 327457, Scopus Author ID: 6603160432
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
I. A. Novikova
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Inna A. Novikova – Dr. Sci. (Medicine), Associate Professor, Deputy Director General for Science, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-6496-9641, eLibrary SPIN: 4810-2424, AuthorID: 726229, Scopus Author ID: 57202252773
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
I. N. Mironenko
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Irina N. Mironenko – Resident Physician, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-2879-467X, eLibrary SPIN: 4571-6413, AuthorID: 1307480
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
A. S. Goncharova
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Anna S. Goncharova – Dr. Sci. (Biology), Head of the Testing Laboratory Center, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0003-0676-0871, eLibrary SPIN: 7512-2039, AuthorID: 553424, Scopus Author ID: 57215862139
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
E. A. Dzhenkova
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Elena A. Dzhenkova – Dr. Sci. (Biology), Professor, Academic Secretary, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-3561-098X, eLibrary SPIN: 6206-6222, AuthorID: 697354, Scopus Author ID: 6507889745
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
O. N. Burov
Southern Federal University
Rostov-on-Don, Russian Federation
Oleg N. Burov – PhD in Chemistry, Associate Professor of the Department of Natural and Macromolecular Compounds, Faculty of Chemistry, Southern Federal University, Rostov-on-Don, Russian Federation ORCID: https://orcid.org/0000-0002-7704-033X, eLibrary SPIN: 5269-7656, AuthorID: 642948, Scopus Author ID: 23033004000, WoS ResearcherID: A-8428-2014
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
O. I. Kit
National Medical Research Centre for Oncology
Rostov-on-Don, Russian Federation
Oleg I. Kit – Dr. Sci. (Medicine), Academician of the Russian Academy of Sciences, Professor, Director General of the National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation ORCID ID: https://orcid.org/0000-0003-3061-6108, eLibrary SPIN: 1728-0329, AuthorID: 343182, Scopus Author ID: 55994103100, WoS ResearcherID: U-2241-2017
Competing Interests:
Oleg I. Kit is the Editor-in-Chief of the Journal «South Russian Journal of Cancer» and one of the authors of the article. Elena A. Dzhenkova and Elena Yu. Zlatnik has been the Member of the Editorial Board of the Journal «South Russian Journal of Cancer» and one of the authors of the article. The article has passed the review procedure accepted in the Journal by independent experts. The authors did not declare any other conflicts of interest.
References
1. Shi C, Yang EJ, Tao S, Ren G, Mou PK, Shim JS. Natural products targeting cancer cell dependency. J Antibiot (Tokyo). 2021 Oct;74(10):677–686. https://doi.org/10.1038/s41429-021-00438-x
2. Morgan E, Arnold M, Gini A, Lorenzoni V, Cabasag CJ, Laversanne M, et al. Global burden of colorectal cancer in 2020 and 2040: incidence and mortality estimates from GLOBOCAN. Gut. 2023;72(2):338-344. https://doi.org/10.1136/gutjnl-2022-327736
3. Zlatnik EYu, Enin YaS, Burov ON, Bondarenko ES, Sagakyants AB, Kutilin DS, et al. Molecular and cellular aspects of the impact of secondary metabolites from common barberry and hybrid goat’s rue on the HeLa cell line. Research and Practical Medicine Journal. 2023;10(4):31–47. (In Russ.). https://doi.org/10.17709/2410-1893-2023-10-4-3
4. Filippova SYu, Timofeeva SV, Sitkovskaya AO, Mezhevova IV, Enin YaS, Burov ON, et al. Influence of berberine on energy phenotype of breast cancer cell cultures. International Journal of Applied and Fundamental Research. 2021;10:42–46. (In Russ.). EDN: CQWAKN
5. Timofeeva SV, Kit OI, Filippova SYu, Sitkovskaya AO, Mezhevova IV, Gnennaya NV, et al. Some Plant Metabolites from Petasítes sp. and Their Effect on Cancer Cells Motility in vitro. Journal of Clinical Oncology. 2022;40(16):15077. https://doi.org/10.1200/jco.2022.40.16_suppl.e15077
6. Timofeeva SV, Zlatnik EY, Vaschenko LN, Enin YS, Nepomnyashchaya EM. Molecular mechanisms of berberine action on tumor cells. Kazan Medical Journal. 2025;106(2):267–276. (In Russ.). https://doi.org/10.17816/kmj643366
7. Li J, Li JX, Jiang H, Li M, Chen L, Wang YY, et al. Phytochemistry and biological activities of corynanthe alkaloids. Phytochemistry. 2023 Sep; 213:113786. https://doi.org/10.1016/j.phytochem.2023.113786
8. Mezhevova IV, Filippova SYu, Chembarova TV, Gnennaya NV, Zlatnik EYu, Novikova IA, et al. Some plant secondary metabolites as promising candidates for the treatment of lung cancer and pancreatic cancer. Problems of Biological, Medical and Pharmaceutical Chemistry. 2024;27(9):32–40. (In Russ.). https://doi.org/10.29296/25877313-2024-09-05
9. Mezhevova IV, Filippova SYu, Timofeeva SV, Sitkovskaya AO, Shamova TV, Enin YaS, et al. Antimigratory effect of berberine in T98G, U87MG and primary glioma cell culture. Journal of Clinical Oncology. 2021;39(S15): e15045.
10. Filippova SY, Shamova TV, Timofeeva SV, Sitkovskaya AO, Mezhevova IV, Gnennaya NV, et al. Influence of some metabolites from plants of the genus Petasítes sp. on cancer cells motility in vitro. Genes & Cells. 2022;17(2):60–63. (In Russ). https://doi.org/10.23868/202209009
11. Ieranò C, Righelli D, D'Alterio C, Napolitano M, Portella L, Rea G, et al. In PD-1+ human colon cancer cells NIVOLUMAB promotes survival and could protect tumor cells from conventional therapies. J Immunother Cancer. 2022 Mar;10(3):e004032. https://doi.org/10.1136/jitc-2021-004032
12. Bovio F, Epistolio S, Mozzi A, Monti E, Fusi P, Forcella M, Frattini M. Role of NEU3 Overexpression in the Prediction of Efficacy of EGFR-Targeted Therapies in Colon Cancer Cell Lines. Int J Mol Sci. 2020 Nov 20;21(22):8805. https://doi.org/10.3390/ijms21228805
13. Shchulkin AV, Tranova YuS, Abalenikhina YuV, Esenina AS, Slepnev AA, Yakusheva EN. Cells of the Caco-2 line as a model for studying the absorption of medicinal substances. Experimental and Clinical Gastroenterology. 2022;(10):63–69. (In Russ.). https://doi.org/10.31146/1682-8658-ecg-206-10-63-69
14. Hoffmann P, Burmester M, Langeheine M, Brehm R, Empl MT, Seeger B, Breves G. Caco-2/HT29-MTX co-cultured cells as a model for studying physiological properties and toxin-induced effects on intestinal cells. PLoS One. 2021 Oct 7;16(10):e0257824. https://doi.org/10.1371/journal.pone.0257824
15. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3722–3727. https://doi.org/10.1073/pnas.0915135107
16. Waghela BN, Vaidya FU, Pathak C. Upregulation of NOX-2 and Nrf-2 Promotes 5-Fluorouracil Resistance of Human Colon Carcinoma (HCT-116) Cells. Biochemistry (Mosc). 2021 Mar;86(3):262–274. https://doi.org/10.1134/s0006297921030044
17. Ghodousi-Dehnavi E, Hosseini RH, Arjmand M, Nasri S, Zamani Z. A Metabolomic Investigation of Eugenol on Colorectal Cancer Cell Line HT-29 by Modifying the Expression of APC, p53, and KRAS Genes. Evid Based Complement Alternat Med. 2021 Nov 18;2021:1448206. https://doi.org/10.1155/2021/1448206
18. Tatar M, Varedi M, Naghibalhossaini F. Epigenetic Effects of Blackberry Extract on Human Colorectal Cancer Cells. Nutr Cancer. 2022;74(4):1446–1456. https://doi.org/10.1080/01635581.2021.1952454
19. Mikhalenko AP, Shchayuk AN, Kilchevsky AV. Signaling pathways: a mechanism for regulating the proliferation and survival of tumor cells. Molekulyarnaya i prikladnaya genetika. 2019;26:145–157. (In Russ.).
20. Filippova SY, Sitkovskaya AO, Timofeeva SV, Shamova TV, Mezhevova IV, Gnennaya NV, Novikova IA. Application of silicone coating to optimize the process of obtaining cellular spheroids by the hanging drop method. South Russian Journal of Cancer. 2022;3(3):15–23. https://doi.org/10.37748/2686-9039-2022-3-3-2
21. Timofeeva SV, Filippova SYu, Sitkovskaya AO, Gnennaya NV, Mezhevova IV, Shamova TV, et al. Bioresource collection of cell lines and primary tumors of the National Medical Research Center of Oncology of the Ministry of Health of Russia. Cardiovascular Therapy and Prevention. 2022;21(11):3397. (In Russ.). https://doi.org/10.15829/1728-8800-2022-3397
22. Li Q, Zhao H, Chen W, Huang P. Berberine induces apoptosis and arrests the cell cycle in multiple cancer cell lines. Arch Med Sci. 2021;19(5):1530–1537. https://doi.org/10.5114/aoms/132969
23. Tarawneh N, Hamadneh L, Abu-Irmaileh B, Shraideh Z, Bustanji Y, Abdalla S. Berberine Inhibited Growth and Migration of Human Colon Cancer Cell Lines by Increasing Phosphatase and Tensin and Inhibiting Aquaporins 1, 3 and 5 Expressions. Molecules. 2023 Apr 29;28(9):3823. https://doi.org/10.3390/molecules28093823
24. Samad MA, Saiman MZ, Abdul Majid N, Karsani SA, Yaacob JS. Berberine Inhibits Telomerase Activity and Induces Cell Cycle Arrest and Telomere Erosion in Colorectal Cancer Cell Line, HCT 116. Molecules. 2021 Jan 13;26(2):376. https://doi.org/10.3390/molecules26020376
25. Li P, Hao Z, Liu H, Zhu B, Dang L, Ma C, et al. Quantitative Proteomics Analysis of Berberine-Treated Colon Cancer Cells Reveals Potential Therapy Targets. Biology (Basel). 2021 Mar 23;10(3):250. https://doi.org/10.3390/biology10030250
26. Gong C, Hu X, Xu Y, Yang J, Zong L, Wang C, et al. Berberine inhibits proliferation and migration of colorectal cancer cells by downregulation of GRP78. Anticancer Drugs. 2020 Feb;31(2):141–149. https://doi.org/10.1097/cad.0000000000000835
27. Duda-Madej A, Viscardi S, Szewczyk W, Topola E. Natural Alkaloids in Cancer Therapy: Berberine, Sanguinarine and Chelerythrine against Colorectal and Gastric Cancer. Int J Mol Sci. 2024;25(15):8375. https://doi.org/10.3390/ijms25158375
28. Och A, Lemieszek MK, Cieśla M, Jedrejek D, Kozłowska A, Pawelec S, Nowak R. Berberis vulgaris L. Root Extract as a Multi-Target Chemopreventive Agent against Colon Cancer Causing Apoptosis in Human Colon Adenocarcinoma Cell Lines. Int J Mol Sci. 2024 Apr 27;25(9):4786https://doi.org/10.3390/ijms25094786
29. Parry RA, Mir IA, Bhat BA, Hussain MU, Ashraf S, Zaman GS, et al. Exploring the cytotoxic effects of bioactive compounds from Alcea rosea against stem cell driven colon carcinogenesis. Sci Rep. 2025 Feb 18;15(1):5892. https://doi.org/10.1038/s41598-025-89714-6.
Review
For citations:
Timofeeva S.V., Filippova S.Yu., Chembarova T.V., Gnennaya N.V., Mezhevova I.V., Zlatnik E.Yu., Novikova I.A., Mironenko I.N., Goncharova A.S., Dzhenkova E.A., Burov O.N., Kit O.I. Antiproliferative properties of a new plant alkaloid against cellular colorectal cancer cultures. South Russian Journal of Cancer. 2025;6(4):16-25. https://doi.org/10.37748/2686-9039-2025-6-4-2. EDN: PHKINR
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