The influences of alkaloids of Chelidonium majus L., Colchicum autumnale L, Catharanthus roseus (L.) G.Don and Vinca minor L. on malignant neoplasms, the review of modern researches.

Keywords: Neoplasms, Colchicine, Vincamine, Vincristine, Vinblastine, Chelidonium majus, Chelidonine

Abstract

natural alkaloids of Chelidonium majus L., Colchicum autumnale L. and Catharanthus roseus  (L.) G.Don are anticancer agents. Some of them, such as colchicine, vincristine and vinblastine, are used in modern medicine, as chemotherapy medicines against malignant neoplasms, some of them are effective supplement to conventional methods or works to prevent cancer onset (chelidonine, sanguinarine, chelerythrine, protopine and allocryptopine). The effect of mitotic poisons that are alkaloids of Colchicum autumnale  colchicine, Catharanthus roseus vincristine and vinblastine against malignant neoplasms began to be studied in the last century, the fact of mitotic spindle violation is given in a large number of works.  However, the mechanisms of apoptosis under their influence have been little studied. The alkaloids of Chelidonium majus and Vinca minor L. have been much less studied, both in clinical studies and experimental ones, including insufficiently researched their anti-proliferative action, the ability to cause apoptosis and its possible mechanism. The research of apoptosis mechanisms caused by natural antitumor agents, will allow creating more effective and saving medicines based on the active ingredients of plant raw materials in the future. The aim of the paper was the analysis of the effect of the main alkaloids of Chelidonium majus, Colchicum autumnale, Catharanthus roseus and Vinca minor on malignant neoplasms and the mechanisms of such an influence with the help of analytic review of foreign and Ukrainian literature for the period 2002-2023 using medical database PubMed.   The researched data obtained on cell lines, laboratory animals (in vitro) and clinic studies were analyzed.  According to the analysis of the literature of recent years, the cytotoxic and anti-proliferative effects of natural alkaloids of Chelidonium majus chelidonine, Colchicum autumnale colchicine, Catharanthus roseus  vincristine and vinblastine and Vinca minor vincamine on malignant neoplasms can be considered proven. Colchicine caused apoptosis in high doses, chelidonine, on the contrary, caused apoptosis of malignant cells in relatively low doses; in large doses it caused autophagy. The signaling pathways of apoptosis mechanisms of malignant cells under the influence of chelidonine, colchicine, vincristine, vinblastine and vincamine are much less studied and require additional research. Most of the results support the mitochondrial pathway, but there is a view in favor of the receptor-mediated pathway. The medicine, which contained alkaloids of Chelidonium majus, showed a positive effect when used in combination with conventional antitumor therapy. Chelidonium majus and Vinca minor alkaloids are candidates for their use

References

Adham Foumani, E., Irani, S., Shokoohinia, Y., & Mostafaie, A. (2022). Colchicine of Colchicum autumnale, A Traditional Anti-Inflammatory Medicine, Induces Apoptosis by Activation of Apoptotic Genes and Proteins Expression in Human Breast (MCF-7) and Mouse Breast (4T1) Cell Lines. Cell journal, 24(11), 647–656. https://doi.org/10.22074/cellj.2022.8290

Al-Rashed, S., Baker, A., Ahmad, S. S., Syed, A., Bahkali, A. H., Elgorban, A. M., & Khan, M. S. (2021). Vincamine, a safe natural alkaloid, represents a novel anticancer agent. Bioorganic chemistry, 107, 104626. https://doi.org/10.1016/j.bioorg.2021.104626

Arora, R. D., & Menezes, R. G. (2021). Vinca Alkaloid Toxicity. In StatPearls. StatPearls Publishing. Bookshelf ID: NBK557842

Angelidis, C., Kotsialou, Z., Kossyvakis, C., Vrettou, A. R., Zacharoulis, A., Kolokathis, F., … Giannopoulos, G. (2018). Colchicine Pharmacokinetics and Mechanism of Action. Current pharmaceutical design, 24(6),659–663. https://doi.org/10.2174/1381612824666180123110042

Chen, X. M., Liu, J., Wang, T., & Shang, J. (2012). Colchicine-induced apoptosis in human normal liver L-02 cells by mitochondrial mediated pathways. Toxicology in vitro : an international journal published in association with BIBRA, 26(5), 649–655. https://doi.org/10.1016/j.tiv.2012.01.024

Cheng, Z., Lu, X., & Feng, B. (2020). A review of research progress of antitumor drugs based on tubulin targets. Translational cancer research, 9(6), 4020–4027. https://doi.org/10.21037/tcr-20-682

Dhyani, P., Quispe, C., Sharma, E., Bahukhandi, A., Sati, P., Attri, D. C., … Cho, W. C. (2022). Anticancer potential of alkaloids: a key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine and vincamine. Cancer cell international, 22(1), 206. https://doi.org/10.1186/s12935-022-02624-9

Ernst, E., & Schmidt, K. (2005). Ukrain - a new cancer cure? A systematic review of randomised clinical trials. BMC cancer, 5, 69. https://doi.org/10.1186/1471-2407-5-69

Gansauge, F., Ramadani, M., Pressmar, J., Gansauge, S., Muehling, B., Stecker, K., … Beger, H. G. (2002). NSC-631570 (Ukrain) in the palliative treatment of pancreatic cancer. Results of a phase II trial. Langenbeck's archives of surgery, 386(8), 570–574. https://doi.org/10.1007/s00423-001-0267-5

Gilca, M., Gaman, L., Panait, E., Stoian, I., & Atanasiu, V. (2010). Chelidonium majus--an integrative review: traditional knowledge versus modern findings. Forschende Komplementarmedizin (2006), 17(5), 241–248. https://doi.org/10.1159/000321397

Habermehl, D., Kammerer, B., Handrick, R., Eldh, T., Gruber, C., Cordes, N., … Jendrossek, V. (2006). Proapoptotic activity of Ukrain is based on Chelidonium majus L. alkaloids and mediated via a mitochondrial death pathway. BMC cancer, 6, 14. https://doi.org/10.1186/1471-2407-6-14

Haque, A., Rahman, M. A., Faizi, M. S. H., & Khan, M. S. (2018). Next Generation Antineoplastic Agents: A Review on Structurally Modified Vinblastine (VBL) Analogues. Current medicinal chemistry, 25(14), 1650–1662. https://doi.org/10.2174/0929867324666170502123639

Havelek, R., Seifrtova, M., Kralovec, K., Krocova, E., Tejkalova, V., Novotny, I., … Rezacova, M. (2016). Comparative cytotoxicity of chelidonine and homochelidonine, the dimethoxy analogues isolated from Chelidonium majus L. (Papaveraceae), against human leukemic and lung carcinoma cells. Phytomedicine: international journal of phytotherapy and phytopharmacology, 23(3),253–266. https://doi.org/10.1016/j.phymed.2016.01.001

Hossain, R., Quispe, C., Saikat, A. S. M., Jain, D., Habib, A., Janmeda, P., … Calina, D. (2022). Biosynthesis of Secondary Metabolites Based on the Regulation of MicroRNAs. BioMed research international, 2022, 9349897. https://doi.org/10.1155/2022/9349897

Koklesova, L., Liskova, A., Samec, M., Qaradakhi, T., Zulli, A., Smejkal, K., … Kubatka, P. (2020). Genoprotective activities of plant natural substances in cancer and chemopreventive strategies in the context of 3P medicine. The EPMA journal, 11(2), 261–287. https://doi.org/10.1007/s13167-020-00210-5

Li, Z., Hu, S., Pu, L. Y., Li, Z., Zhu, G., Cao, Y,… Wu, Z. (2022). Design, synthesis and biological evaluation of a novel colchicine-magnolol hybrid for inhibiting the growth of Lewis lung carcinoma in Vitro and in Vivo. Frontiers in chemistry, 10, 1094019. https://doi.org/10.3389/fchem.2022.1094019

Lin, Z. Y., Yeh, M. L., Huang, C. I., Chen, S. C., Huang, C. F., Huang, J. F., … Chuang, W. L. (2021). Potential of novel colchicine dosage schedule for the palliative treatment of advanced hepatocellular carcinoma. The Kaohsiung journal of medical sciences, 37(7), 616–623. https://doi.org/10.1002/kjm2.12374

Macedo, T. R., de Queiroz, G. F., Casagrande, T. A. C., Alexandre, P. A., Brandão, P. E., Fukumasu, H., … Matera, J. M. (2022). Imatinib Mesylate for the Treatment of Canine Mast Cell Tumors: Assessment of the Response and Adverse Events in Comparison with the Conventional Therapy with Vinblastine and Prednisone. Cells, 11(3), 571. https://doi.org/10.3390/cells11030571

Noureini, S. K., & Esmaili, H. (2014). Multiple mechanisms of cell death induced by chelidonine in MCF-7 breast cancer cell line. Chemico-biological interactions, 223, 141–149. https://doi.org/10.1016/j.cbi.2014.09.013

Noureini, S. K., & Wink, M. (2009). Transcriptional down regulation of hTERT and senescence induction in HepG2 cells by chelidonine. World journal of gastroenterology, 15(29), 3603–3610. https://doi.org/10.3748/wjg.15.3603

Ossowska, M., Picornell, J. A., Finotello, R., Amores-Fuster, I., & Tanis, J. B. (2023). Pre-operative neoadjuvant vinblastine-prednisolone in canine mast cell tumours: A single-centre retrospective cohort study. Veterinary and comparative oncology, 21(3), 447–459. https://doi.org/10.1111/vco.12904

Papaliagkas, V., Anogianaki, A., Anogianakis, G., & Ilonidis, G. (2007). The proteins and the mechanisms of apoptosis: a mini-review of the fundamentals. Hippokratia, 11(3), 108–113.

Paul, A., Bishayee, K., Ghosh, S., Mukherjee, A., Sikdar, S., Chakraborty, … Khuda-Bukhsh, A. R. (2012). Chelidonine isolated from ethanolic extract of Chelidonium majus promotes apoptosis in HeLa cells through p38-p53 and PI3K/AKT signalling pathways. Zhong xi yi jie he xue bao = Journal of Chinese integrative medicine, 10(9), 1025–1038. https://doi.org/10.3736/jcim20120912

Sharifi-Rad, J., Quispe, C., Butnariu, M., Rotariu, L. S., Sytar, O., Sestito, S., … Calina, D. (2021). Chitosan nanoparticles as a promising tool in nanomedicine with particular emphasis on oncological treatment. Cancer cell international, 21(1), 318. https://doi.org/10.1186/s12935-021-02025-4

Sharifi-Rad, J., Quispe, C., Patra, J. K., Singh, Y. D., Panda, M. K., Das, G., … Calina, D. (2021). Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy. Oxidative medicine and cellular longevity, 2021, 3687700. https://doi.org/10.1155/2021/3687700

Shen, L., Lee, S., Joo, J. C., Hong, E., Cui, Z. Y., Jo, E., …Jang, H. J. (2022). Chelidonium majus Induces Apoptosis of Human Ovarian Cancer Cells via ATF3-Mediated Regulation of Foxo3a by Tip60. Journal of microbiology and biotechnology, 32(4), 493–503. https://doi.org/10.4014/jmb.2109.09030

Škubník, J., Pavlíčková, V. S., Ruml, T., & Rimpelová, S. (2021). Vincristine in Combination Therapy of Cancer: Emerging Trends in Clinics. Biology, 10(9), 849. https://doi.org/10.3390/biology10090849

Stiborova, K., Treggiari, E., Amores-Fuster, I., Del Busto, I., Killick, D., Maddox, T., …Blackwood, L. (2019). Haematologic toxicity in dogs with mast cell tumours treated with vinblastine/prednisolone chemotherapy with/without radiotherapy. The Journal of small animal practice, 60(9), 534–542. https://doi.org/10.1111/jsap.13047

Todd, J. E., Nguyen, S. M., White, J., Langova, V., Thomas, P. M., & Tzannes, S. (2021). Combination vinblastine and palladia for high-grade and metastatic mast cell tumors in dogs. The Canadian veterinary journal = La revue veterinaire canadienne, 62(12), 1335–1340.

Wen X, Lin ZQ, Liu B, Wei YQ. Caspase-mediated programmed cell death pathways as potential therapeutic targets in cancer. Cell Prolif. 2012 Jun;45(3):217-24. doi: 10.1111/j.1365-2184.2012.00814.x. Epub 2012 Mar 20. PMID: 22429822; PMCID: PMC6495317.

Дашутіна, С. Л. (2003). Стандартизація препаратів на основі діючих речовин чистотілу. Фармаком, (3), 41-45.

Камінський В.О., 2006. Механізми індукції апоптозу у лімфомних клітинах під впливом алкалоїдів чистотілу. автореф. дис... канд. біол. наук: 03.00.11; НАН України, Інститут біології клітини. Національна бібліотека України ім.В.І.Вернадського. РА345963

Ковальчук, В. М., Гуля, Б. М., Лучкiв, В. I., Іванчук, І. З., Тащієв, Р. К., Потопальський, А. І., & Потопальська, Ю. А. (2006). Використання протипухлинного препарату з групи алкілованих тіофосфамідом алкалоїдів чистотілу великого при злоякісних новоутвореннях шиї без первинного осередку. Онкологія, 8(3), 278-280.

URI: http://dspace.nbuv.gov.ua/handle/123456789/19556

Published
2023-10-27
How to Cite
1.
Pavlenko O, Strokina I. The influences of alkaloids of Chelidonium majus L., Colchicum autumnale L, Catharanthus roseus (L.) G.Don and Vinca minor L. on malignant neoplasms, the review of modern researches. USMYJ [Internet]. 2023Oct.27 [cited 2026Mar.21];142(4):145-52. Available from: https://mmj.nmuofficial.com/index.php/journal/article/view/133
Section
Pharmacy, industrial pharmacу