<<<  Back

2021, № 91

UDC: 615.03
GSNTI: 76.31.39, 76.31.31

Cytotoxic activity of extracts obtained from intact plant and callus cell culture Podophyllum peltatum in human leukemic cells

Plants of the genus Podophyllum are used in traditional medicine in North America, China, Tibet, India. In scientific medicine, a number of biological effects of extracts, fractions and mono compounds of these plants have been discovered and are actively used: antiviral (including for the treatment of COVID-19), antibacterial, antioxidant, antifungal, antimalarial, antitumor, insecticidal, anti-inflammatory, radioprotective and some other effects. The antitumor activity of compounds contained in plants of the genus Podophyllum (primarily phenolic compounds and alkaloids) was determined for cancer of the colon, cervix, breast, lungs (including small cell), ovaries, prostate, promyelocytic leukemia, hepatocircular carcinoma, genital and anogenital warts. These compounds are secondary plant metabolites. They are trying to get them not only from plant, but also from biotechnological raw materials (callus and suspension cultures, cultures of bearded roots). A callus cell culture was obtained from three parts of an intact Podophyllum peltatum plant (root, kidney, and fetus) at All-Russian Scientific Research Institute of Medicinal and Aromatic Plants. Under in vitro conditions, the resazurine-test revealed a pronounced cytotoxic activity of the extract of rhizomes with roots, leaves, and callus cell culture of P. peltatum against human leukemic cells of the K562 line. When tumor cells were incubated with extracts of four different concentrations for 72 hours, the viability of tumor cells was inhibited by 61,0-69,0, leaf extract - by 45,0-76,0%, callus cell extract obtained from the fetus, kidney and root - by 46,0-48,0%. Extracts from rhizomes with roots had the greatest cytotoxic effect. Extracts from native raw materials showed a higher cytotoxic activity than extracts from callus cultures. Moreover, callus cultures showed cytotoxic activity against leukemic cells only at the maximum concentration of the extract, and extracts from native raw materials - in the entire studied concentration range.
Keywords: Podophyllum peltatum, cytotoxic activity, leukemic cells, K562, resazurin-test, Alamar Blue, phenolic compounds, podophyllotoxin.
DOI: 10.21515/1999-1703-91-147-151

References:

1. Ardalani, H. Podophyllotoxin: a novel potential natural anticancer agent / H. Ardalani, A. Avan, M. Ghayour-Mobarhan // Avicenna Journal of Phytomedicine. - 2017. - No. 7 (4). - Р. 285-294.
2. Kumar, P. Expression analysis of biosynthetic pathway genes vis-à-vis podophyllotoxin content in Podophyllum hexandrum Royle / P. Kumar, T. Pal, N. Sharma, V. Kumar, H. Sood, R. S. Chauhan // Protoplasma. - 2015. - No. 252 (5). - P. 1253-1262.
3. Kumar, P. Comparative whole-transcriptome analysis in Podophyllum species identifies key transcription factors contributing to biosynthesis of podophyllotoxin in P. hexandrum / P. Kumar, V. Jaiswal, T. Pal, J. Singh, R. S. Chauhan // Protoplasma. - 2017. - No. 254 (1). - Р. 217-228.
4. Zhao, W. Challenges and potential for improving the druggability of podophyllotoxin-derived drugs in cancer chemotherapy / W. Zhao, Y. Cong, H.-M. Li, Sh. Li, Y. Shen, Q. Qi, Y. Zhang, Y.-Zh. Li, Y.-J. Tang // Natural P roduct Reports. - 2021. - No. 38 (3). - Р. 470-488.
5. Chen, H. The Effect of h-53-R249S on the Supression of Hepatocellular Carcinoma Cells Survival Induced by Podophyllum Derivatives / H. Chen, M. Zhang, Z. Wang, L. Li, Q. Li, H. Wang // Anti-Сancer Agentsin Medicinal Chemistry. - 2020. - No. 20 (7). - Р. 865-874.
6. Mazzio, E. High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells / E. Mazzio, R. Badisa, N.Mack, S. Deiab, K. F. Soliman, // Phytoterapy Research. - 2014. - No. 28(6). - Р. 856-867.
7. Hu, Sh. Anticancer effect of deoxypodophyllotoxin induces apoptosis of human prostate cancer cells / Sh. Hu, Q. Zhou, W.-R. Wu, Yi-X. Duan, Z.-Y. Gao, Y.-W. Li, Q. Lu // Oncology Letters. - 2016. - No. 12(4). - Р. 2918-2923.
8. Avula, Bh. Rapid analysis of lignans from leaves of Podophyllum peltatum L. samples using UPLC-UV-MS / Bh. Avula, Y.-H. Wang, R. M. Moraes, I. A. Khan // Biomedical Chromatography. - 2011. - No. 25 (11). -Р. 1230-1236.
9. Butt, T. I. Ethnopharmacology, phytochemistry and cytotoxicity of emerging biotechnological tool: Mayapple (Podophyllum hexandrum L.: Berberidaceae) / T. I. Butt, M. Sh. Amjad // Journal of Coastal Life Medicine. - 2015. - No. 3 (8). - Р. 652-657.
10. Marques, J. V. A multi-omics strategy resolves the elusive nature of alkaloids in Podophyllum species / J. V. Marques, D. S. Dalisay, H. Yang, Ch. Lee, L. B. Davin, N. G. Lewis // Molecular BioSystems. - 2014. - No. 10 (11). - Р. 2838-49.
11. Rajesh, M. An efficient in vitro system for somatic embryogenesis and podophyllotoxin production in Podophyllum hexandrum Royle / M. Rajesh, G. Sivanandhan, M. Jeyaraj, R. Chackravarthy, M. Manickavasagam, N. Selvaraj, A. Ganapathi // Protoplasma. - 2014. - No. 251 (5). - Р. 1231-43.
12. Kumari, A. Biotechnological interventions for harnessing podophyllotoxin from plant and fungal species: current status, challenges, and opportunities for its commercialization / A. Kumari, Dh. Singh, S. Kumari // Critical Reviews in Biotechnology. - 2017. - No. 37(6). - Р. 739-753.
13. Lau, W. Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone / W. Lau, E. S. Sattely // Science. - 2015. - No. 349 (6253). - Р. 1224-1228.
14. Bai, J.-K. Novel biotransformation process of podophyllotoxin to 4β-sulfur-substituted podophyllum derivates with anti-tumor activity by Penicillium purpurogenum Y.J. Tang / J.-K. Bai, W. Zhao, H.-M. Li, Y.-J. Tang // Current Medicinal Chemistry. -2012. - No. 19 (6). - Р. 927-936.
15. Yousefzadi, M. Optimization of podophyllotoxin extraction method from Linum album cell cultures / M. Yousefzadi, M. Sharifi, N. A. Chashmi, M. Behmanesh, A. Ghasempour // Pharmaceutical Biology. - 2010. - No. 48 (12). - Р. 1421-1425.
16. Engström, M. T. Rapid Fingerprint Analysis of Plant Extracts for Ellagitannins, Gallic Acid, and Quinic Acid Derivatives and Quercetin-, Kaempferol- and Myricetin-Based Flavonol Glycosides by UPLC-QqQ-MS/MS / M. T. Engström, M. Pälijärvi, J.-P. Salminen // Journal of agricultural and food chemistry. -2015. - No. 63 (16). - Р. 4068-4079.
17. Иксанова, А. Г. Методы исследования цитотоксичности при скрининге лекарственных препаратов / А. Г. Иксанова, О. В. Бондарь, К. В. Балакин. - Казань: Казанский университет, 2016. - 40 с.

Authors:

1. Kitaeva Maria Petrovna, PhD student, Federal State Budgetary Scientific Institution "All-Russian Scientific Research Institute of Medicinal and Aromatic Plants".
2. Fedotcheva Tatyana Alexandrovna, PhD, Assistant professor, Federal State Budgetary Scientific Institution "All-Russian Scientific Research Institute of Medicinal and Aromatic Plants".
3. Semeykin Alexandr Vladimirovich, PhD, Assistant professor, Federal State Autonomous Educational Institution of Higher Education Russian Research Medical University named after N. I. Pirogov.