Influence of Polysaccharide from Helianthus tuberosus L. on Antiproliferative Activity of N-Glycoside Indolo[2,3-a]carbazole Derivative LCS-1269

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

The Lewis model of epidermoid carcinoma that developed in the lungs of F1(C57Bl/6 × DBA/2) hybrid mice has been used while investigating antitumor activity of the N-glycoside derivative indolo[2,3-a]carbazole (LCS-1269) with a polysaccharide from Helianthus tuberosus L. as an adjuvant agent. The antitumor effect of LCS-1269 together with the polysaccharide was evaluated by the inhibition of tumor growth in treated ani mals in comparison to the control group. As a result, it was found that combination of LCS-1269 with the polysaccharide from Helianthus tuberosus L. provided more pronounced therapeutic and longer-lasting effect than monotherapy showing a 53–64% decrease in growth of Lewis lung carcinoma for up to a 28-day obser vation period. Polysaccharide supplementation led to an increase in the number of blood cells leukocytes, lymphocytes and phagocytes responsible for antitumor immunity. The chemotherapy in combination with LCS-1269 and polysaccharide had a pronounced sustained antitumor effect on Lewis lung carcinoma in the peripheral blood system of mice in presence of a temporarily increased level of neutrophils and monocytes by the 12th day of tumor development. Apparently, the tested compounds stimulated proliferation of neutrophils and monocytes of certain phenotypes with antitumor activity at an earlier stage of Lewis lung carcinoma de velopment.

About the authors

M. P Kiseleva

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

Email: marina-kiselyova@mail.ru
Moscow, 115522 Russia

I. S Golubeva

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

Moscow, 115522 Russia

V. P Deryagina

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

Moscow, 115522 Russia

A. V Lantsova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

Moscow, 115522 Russia

L. V Ektova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

Moscow, 115522 Russia

E. A Kornyushenkov

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

Moscow, 115522 Russia

L. M Borisova

N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian Federation

Moscow, 115522 Russia

E. A Generalov

M.V. Lomonosov Moscow State University

Moscow, 119991 Russia

References

  1. Heidkamp J., Scholte M., Rosman C., Manohar S., Fütterer J. J., and Rovers M. M. Novel imaging techniques for intraoperative margin assessment in surgical oncology: A systematic review. Int. J. Cancer, 149 (3), 635–645 (2021). doi: 10.1002/ijc.33570
  2. Cha J. H., Chan L. C., Song M. S., and Hung M. C. New approaches on cancer immunotherapy. Cold Spring Harb. Perspect. Med., 10 (8), a036863 (2020). doi: 10.1101/cshperspect.a036863
  3. Анисимов М. Н. и Гудимчук Н. Б. «Зоопарк» ингибиторов динамики микротрубочек. Природа, № 8, 3– 12 (2020). doi: 10.7868/S0032874X20080013
  4. Dona Lemus O. M., Cao M., Cai B., Cummings M., and Zheng D. Adaptive radiotherapy: next-generation radiotherapy. Cancers, 16 (6), 1206 (2024). doi: 10.3390/cancers16061206
  5. Karati D. and Kumar D. A Comprehensive review on targeted cancer therapy: new face of treatment approach. Curr. Pharm. Des., 29 (41), 3282–3294 (2023). doi: 10.2174/0113816128272203231121034814
  6. Siegel R. L., Giaquinto A. N., and Jemal A. Cancer statistics, 2024 [erratum in CA Cancer J. Clin., 74 (2), 203 (2024)]. CA Cancer J. Clin., 74 (1), 12–49 (2024). doi: 10.3322/caac.21820
  7. Yu Y., Shen M., Song Q., and Xie J. Biological activities and pharmaceutical applications of polysaccharide from natural resources: a review. Carbohydr. Polym., 183, 91– 101 (2018). doi: 10.1016/j.carbpol.2017.12.009
  8. Generalov E. A. Antimetastatic and tumor growth inhibition activity of polysaccharide from Helianthus tuberosus L. ARC J. Cancer Sci., 1 (1), 5–10 (2015). doi: 10.20431/2455-6009.0101002
  9. Du H., Jin X., Jin S., Zhang D., Chen Q., Jin X., Wang C., Qian G., and Ding H. Anti-leukemia activity of polysaccharide from sargassum fusiforme via the pi3k/akt/bad pathway in vivo and in vitro. Mar. Drugs, 21 (5), 289 (2023). doi: 10.3390/md21050289.
  10. Li M., Liu Y., Zhang H., Liu Y., Wang W., You S., Hu X., Song M., Wu R., and Wu J. Anti-cancer potential of polysaccharide extracted from Polygonatum sibiricum on HepG2 cells via cell cycle arrest and apoptosis. Front. Nutr., 9, 1054565 (2022). doi: 10.3389/fnut.2022.938290
  11. Yue L., Cui H., Li C., Lin Y., Sun Y., Niu Y., Wen X., and Liu J. A polysaccharide from Agaricus blazei attenuates tumor cell adhesion via inhibiting E-selectin expression. Carb. Pol., 88 (4), 1326–1333 (2012). doi: 10.1016/j.carbpol.2012.02.015
  12. Cao R., Jin W., Shan Y., Wang J., Liu G., Kuang S., and Sun C. Marine bacterial polysaccharide EPS11 inhibits cancer cell growth via blocking cell adhesion and stimulating anoikis. Mar. Drugs, 16 (3), 85 (2018). doi: 10.3390/md16030085.
  13. Ping Z., Xu H., Liu T., Huang J., Meng Y., Xu X., Li W., and Zhang L. Anti-hepatoma activity of the stiff branched β-d-glucan and effects of molecular weight. J. Mater. Chem. B, 4 (26), 4565–4573 (2016). doi: 10.1039/c6tb01299j.
  14. Jiang Z., Chi J., Li H., Wang Y., Liu W., and Han B. Effect of chitosan oligosaccharide-conjugated selenium on improving immune function and blocking gastric cancer growth. Eur. J. Pharmacol., 891, 173673 (2020). doi: 10.1016/j.ejphar.2020.173673.
  15. Guo R., Chen M., Ding Y., Yang P., Wang M., Zhang H., He Y., and Ma H. Polysaccharides as potential anti-tumor biomacromolecules – a review. Front. Nutr., 9, 838179 (2022). doi: 10.3389/fnut.2022.838179
  16. Li W., Song K., Wang S., Zhang C., Zhuang M., Wang Y., and Liu T. Anti-tumor potential of astragalus polysaccharides on breast cancer cell line mediated by macrophage activation. Mater. Sci. Eng. C. Mater. Biol. Appl., 98, 685– 695 (2019). doi: 10.1016/j.msec.2019.01.025.
  17. Bao X., Yuan H., Wang C., Liu J., and Lan M. Antitumor and immunomodulatory activities of a polysaccharide from Artemisia argyi. Carbohydr Polym., 98, 1236–1243 (2013). doi: 10.1016/j.carbpol.2013.07.018
  18. Liu Y., Zhang L., Zhu X., Wang Y., Liu W., and Gong W. Polysaccharide Agaricus blazei Murill stimulates myeloid derived suppressor cell differentiation from M2 to M1 type, which mediates inhibition of tumour immune-evasion via the toll-like receptor 2 pathway. Immunology, 146 (3), 379–391 (2015). doi: 10.1111/imm.12508.
  19. Khan T., Date A., Chawda H., and Patel K. Polysaccharides as potential anticancer agents – a review of their progress. Carbohydr. Polym., 210, 412–428 (2019). doi: 10.1016/j.carbpol.2019.01.064
  20. Generalov E. A. Study of the structure and immunoenhancing activity of glucan ADVA. Moscow Univ. Phys., 68, 470–477 (2013). doi: 10.3103/S0027134913060040
  21. Pang G., Wang F., and Zhang L. W. Dose matters: direct killing or immunoregulatory effects of natural polysaccharides in cancer treatment. Carbohydr. Polym., 195, 243– 256 (2018). doi: 10.1016/j.carbpol.2018.04.100.
  22. Gao X. and Homayoonfal M. Exploring the anti-cancer potential of Ganoderma lucidum polysaccharides (GLPs) and their versatile role in enhancing drug delivery systems: a multifaceted approach to combat cancer. Cancer Cell Int., 23 (1), 324 (2023). doi: 10.1186/s12935-023-03146-8.
  23. Safonova E. A., Lopatina K. A., Razina T. G., Zueva E. P., Fedorova E. P., Gur'ev A. M., and Belousov M. V. Modification of the myelotoxic and antitumor effects of polychemotherapy by polysaccharides from Tussilago farfara L. Bull. Exp. Biol. Med., 166 (2), 197–200 (2016). doi: 10.1007/s10517-018-4313-5
  24. Zenkov R. G., Ektova L. V., Vlasova O. А., Belitskiy G. А., Yakubovskaya M. G., and Kirsanov K. I. Indolo[2,3a]carbazoles: diversity, biological properties, application in antitumor therapy. Chem. Heterocyc. Comp., 56 (6), 644–658 (2020). doi: 10.1007/s10593-020-02714-4
  25. Kozin D. A., Shprakh Z. S., Reshetnyak V. Yu., Nesterova O. V., Avertseva I. N., and Rodionova G. M. Indolo[2,3-a]carbazole derivatives with antitumor activity and instrumental methods for their investigation. Drug Dev. Registr., 9 (4), 15–20 (2020). doi: 10.33380/2305-2066-2020-9-4-128-135
  26. Kolpaksidi A. P., Dmitrieva M. V., Yarosh I. V., and Krasnyuk I. I. Antitumor drugs based on indolocarbazol derivatives. Pharmacy & Pharmacol., 9 (4), 252–265 (2021). doi: 10.19163/2307-9266-2021-9-4-252-265
  27. Éktova, L. V., Goryunova, O. V., Eremina, V. A., Tikhonova N. I., and Medvedeva L. A. An improved method for the synthesis of the of indole[2,3-a]pyrrolo[3,4-c]carbazole-5,6-dione N-glycosides and their cytotoxic activity. Pharm. Chem. J., 53, 604–609 (2019). doi: 10.1007/s11094-019-02046-4
  28. Николаева Л. Л., Ланцова А. В., Санарова Е. В., Орлова О. Л., Оборотов А. В., Игнатьева Е. В., Шпрах З. С., Кульбачевская Н. Ю. и Коняева О. И. Разработка состава и технологии получения модели инъекционной формы производного индолокарбазола. Хим.-фармацевт. журн., 57 (6), 42–46 (2023). doi: 10.30906/0023-1134-2023-57-6-42-46
  29. Vartanian A., Golubeva I., and Shprakh Z. Is vasculogenic mimicry a hallmark of an aggressive tumor? In: Horiz. Cancer Res. (Nova Science Publishers, Inc., 2017), v. 65, pp. 13–33.
  30. Vartanian A., Misyurin V. A., Baryshnikova M. A., and Shprakh Z. Inhibitor of vasculogenic mimicry restores sensitivity of resistant melanoma cells to DNA-damaging agents. Melanoma Res., 27 (1), 8–16 (2017). doi: 10.1097/CMR.0000000000000308
  31. Generalov E. A. Water-soluble polysaccharide from Heliantnus tuberosus L.: radioprotective, colony-stimulation and immunomodulation activities. Biophysics, 60 (1), 73– 79 (2015).
  32. Generalov E. and Yakovenko L. Receptor basis of biological activity of polysaccharides. Biophys. Rev., 15, 1209–1222 (2023). doi: 10.1007/s12551-023-01102-4
  33. Generalov E. A. and Afremova A. I. The Molecular mechanism of the action of Helianthus tuberosus L. polysaccharide. Biophysics, 61, 558–564 (2016). doi: 10.1134/S0006350916040096
  34. Kalitin N. N., Ektova L. V., Kostritsa N. S., Sivirinova A. S., Kostarev A. V., Smirnova G. B., Borisova Y. A., Golubeva I. S., Ermolaeva E. V., Vergun M. A., Babaeva M. A., Lushnikova A. A., and Karamysheva A. F. A novel glycosylated indolocarbazole derivative LCS1269 effectively inhibits growth of human cancer cells in vitro and in vivo through driving of both apoptosis and senescence by inducing of DNA damage and modulating of AKT/mTOR/S6K and ERK pathways. Chem. Biol. Interact., 364, 110056 (2022). doi: 10.1016/j.cbi.2022.110056
  35. Голубева И. С., Яворская Н. П., Эктова Л. В., Дмитриева М. В., Борисова Л. М., Еремина В. А., Тихонова Н. И. и Пугачева Р. Б. Противоопухолевая активность некоторых производных N-гликозидов индоло[2,3-a]карбазолов с углеводным остатком ксилозой. Рос. биотерапевтич. журн., 19 (4), 86–93 (2020). doi: 10.17650/1726-9784-2020-19-4-86-93
  36. Zenkov R. G., Vlasova O. A., Maksimova V. P., Fetisov T. I., Karpechenko N. Y., Ektova L. V., Eremina V. A., PopovaV. G., Usalka O. G., Lesovaya E. A., Belitsky G. A., Yakubovskaya M. G., and Kirsanov K. I. Molecular mechanisms of anticancer activity of N-glycosides of indolocarbazoles LCS-1208 and LCS-1269. Molecules, 26 (23), 7329 (2021). doi: 10.3390/molecules26237329
  37. Directive 2010/63/EU of the European Parliament and of the Council on the protection of animals used for scientific purposes. | FAOLEX n.d. URL: https://www.fao.org/faolex/results/details/ru/c/LEX-FAOC098296/ (accessed: 30.08.2023).
  38. Трещалина Е. М., Смирнова Г. Б. и Андронова Н. В. Коллекция опухолевых штаммов животных для экспериментальной химиотерапии злокачественных опухолей (Практическая медицина, М., 2022).
  39. Трещалина Е. М., Жукова О. С., Герасимова Г. К., Андронова Н. В. и Гарин А. М. Методические рекомендации по доклиническому изучению противоопухолевой активности лекарственных средств. В сб. Руководство по проведению доклинических исследований лекарственных средств. Под ред. А. Н. Миронова и др. («Гриф и К», М., 2012), ч. 1, сс. 640–657.
  40. Гольдберг Е. Д., Дыгай А. М. и Шахов В. П. Методы культуры ткани в гематологии (Изд-во Томского университета, Томск, 1992).
  41. Экспериментальная оценка противоопухолевых препаратов в СССР и США. Под ред. З. П. Софьиной, А. Б. Сыркина, А. Голдина и А. Кляйна (Медицина, М., 1980).
  42. Крицкая К. А., Петренко В. С., Ларюшкин Д. П., Наумов А. А. и Поцелуева М. М. Действие различных концентраций хелатора железа (дефероксамина), на клетки асцитной карциномы ЭРЛИХА in vitro. В сб. Матер. 22-й Международной Пущинской школы-конференции молодых ученых «Биология наука XXI века» (Синхробук, Пущино, 2018), с. 352. EDN: URYPPS

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Russian Academy of Sciences