Some plant secondary metabolites as promising candidates for the treatment of lung cancer and pancreatic cancer

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Abstract

Introdution. Cancer is the second leading cause of death in Russia and the world after cardiovascular diseases. Chemotherapy remains the main line of treatment, but tumor cells can become resistant to drugs. Researchers are working on new effective drugs, including secondary metabolites of plants that have antitumor effects through various mechanisms.

The aim of this study was to investigate the cytotoxic properties of three compounds: alkaloid P1, terpenoid P2, and flavonoid V1 against pancreatic cancer cell line AsPC-1 and non-small cell lung cancer H1299.

Material and methods. Secondary metabolites of Petasites hybrydicus (L.) G. Gaertn., B. Mey. & Scherb. and Viscum album L. were extracted using tetrachloroethylene. For identification of the isolated compounds, high-performance liquid chromatography with mass detection and nuclear magnetic resonance method were used. Non-small cell lung cancer cell line H1299 and pancreatic cancer AsPC-1 were grown in RPMI1640 medium (Gibco, USA) supplemented with 10% FBS (HyClone, USA) and 1% glutamine (Biolot, Russia) under standard conditions. Cell sensitivity to the studied compounds was determined by MTT test.

Results. All three compounds demonstrated antitumor activity against the studied cell lines. Compound V1 increased signs of mesenchymal cells morphology and apoptosis, with IC₅₀ values of 234. 24±21. 56 μM (AsPC-1) and 565. 62±84. 31 μM (H1299). Compound P1 promoted multinucleated cell formation in H1299 culture. Half-inhibitory doses for P1 were 652. 54±56. 12 μM (AsPC-1) and 157. 85±48. 62 μM (H1299). Compound P2 induces cell apoptosis and necrosis and probably affects membrane rigidity. The IC₅₀ values for P2 were 802. 34±121. 02 μM (AsPC-1) and 415. 71±75. 05 μM (H1299).

Conclusions. These compounds can be considered promising antitumor agents for lung cancer and pancreatic cancer.

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About the authors

I. V. Mezhevova

National medical research centre for Oncology

Author for correspondence.
Email: mezhevova88@gmail.com
ORCID iD: 0000-0002-7902-7278

Junior Research Scientist

Russian Federation, 63, 14-line str., Rostov-on-Don, 344037

S. Yu. Filippova

National medical research centre for Oncology

Email: svetlana.filippova1982@gmail.com
ORCID iD: 0000-0002-4558-5896

Research Assistant

Russian Federation, 63, 14-line str., Rostov-on-Don, 344037

T. V. Chembarova

National medical research centre for Oncology

Email: tanyshamova@mail.ru
ORCID iD: 0000-0002-4555-8556

Junior Research Scientist

 

Russian Federation, 63, 14-line str., Rostov-on-Don, 344037

N. V. Gnennaya

National medical research centre for Oncology

Email: ngnennaya@inbox.ru
ORCID iD: 0000-0002-3691-3317

Junior Research Scientist

Russian Federation, 63, 14-line str., Rostov-on-Don, 344037

E. Yu. Zlatnik

National medical research centre for Oncology

Email: elena-zlatnik@mail.ru
ORCID iD: 0000-0002-1410-122X

Dr. Sc. (Med.), Professor, Leading Research Scientist

Russian Federation, 63, 14-line str., Rostov-on-Don, 344037

I. A. Novikova

National medical research centre for Oncology

Email: novikovainna@yahoo.com
ORCID iD: 0000-0002-6496-9641

Dr. Sc. (Med.), Deputy. General Director for Science

Russian Federation, 63, 14-line str., Rostov-on-Don, 344037

Y. S. Enin

National medical research centre for Oncology

Email: dendro51@yandex.ru
ORCID iD: 0000-0002-4572-1579

Research Assistant

Russian Federation, 63, 14-line str., Rostov-on-Don, 344037

O. N. Burov

Southern Federal University

Email: bboleg@gmail.com
ORCID iD: 0000-0002-7704-033X

Ph. D. (Chem.), Associate Professor

Russian Federation, 105/42, Bolshaya Sadovaya str., Rostov-on-Don, 344006

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Supplementary files

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2. Fig. 1. Structural formulas of the compounds tested in the study. Explanations in the text

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3. Fig. 2. Antiproliferative activity of selected plant metabolites on H1299 and AsPC-1 cultures, exposure 72 hours: A – dose-response curve for V1; B – dose-response curve for P1; B – dose-response curve for P2

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4. Fig. 3. Cytopathic effect of the studied compounds on H1299 and AsPC-1 cultures, exposure 72 hours: A – AsPC-1, control; Б – AsPC-1, 625 µM V1; B – AsPC-1, 343 µM P1; Г – AsPC-1, 793 µM P2; Д – H1299, control; E – H1299, 625 µM V1; Ж – H1299, 343 µM P1; З – H1299, 793 µM P2. Designations: ПК – leading edge of migrating cells, МК – multinucleated cell, black arrows – cells with signs of apoptosis, white arrows – cells with signs of necrosis. Lens magnification 10×

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