Indicators of the nitric oxide system in mitochondria of non-small cell lung cancer in men
DOI: 10.32364/2587-6821-2026-10-9-15
Indicators of the nitric oxide system in mitochondria of non-small cell lung cancer in men
E.M. Frantsiyants1, V.A. Bandovkina1, D.A. Kharagezov1, I.V. Neskubina1, E.I. Surikova1, Yu.A. Petrova1, N.D. Cheryarina1, T.R. Nashemukov1, A.G. Mamlina2
1 National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation
2 Rostov State Medical University, Rostov-on-Don, Russian Federation
Aim: to study parameters related to nitric oxide (NO) production in mitochondria isolated from tumor tissue and resection line tissue in men with squamous cell lung cancer and lung adenocarcinoma.
Materials and Methods: mitochondria were isolated from tumor and resection line tissue samples resulted from radical surgeries in 37 male patients with newly diagnosed stage II–IIIA non-small cell lung cancer (NSCLC). Two groups of NSCLC patients with squamous cell carcinoma (n=18) and adenocarcinoma (n=19) were studied. Mitochondria were isolated by differential centrifugation with additional purification in Percoll gradient. In mitochondrial samples, arginine, asymmetric dimethylarginine (ADMA), L-citrulline, nitrotyrosine, nitrates, total and endogenous nitrite, as well as NOS2 and NOS3 were assayed by enzyme-linked immunosorbent assay.
Results: in adenocarcinoma mitochondria, NOS2 and NOS3 levels increased 2-fold and 1.5-fold, respectively, and L-citrulline level increased 3.7-fold, while arginine level decreased 3-fold and ADMA level decreased 1.5-fold compared with the resection line tissue. At the same time, nitrate, nitrite and nitrotyrosine levels did not differ from those in the resection line tissue. In contrast with with the resection line tissue, NOS2, arginine and L-citrulline levels increased 1.6-fold, 1.3-fold and 1.7-fold, respectively, while NOS3 level decreased 4.3-fold in squamous cell cancer mitochondria. Along with this, levels of nitrates, total nitrite, and endogenous nitrite decreased 3.1-fold, 1.9-fold, and 1.6-fold, respectively; nitrotyrosine level increased by 2.3 times.
Conclusion: in adenocarcinoma tissue mitochondria, NO is produced via a canonical NOS-dependent pathway with arginine conversion to L-citrulline, whereas the non-canonical pathway (i. e., from nitrites) is suppressed. In case of squamous cell carcinoma, the non-canonical pathway of NO production dominates, and it is associated with pronounced nitrosative stress (elevated nitrotyrosine level) and depletion of nitrites and nitrates. However, contribution of the canonical pathway cannot be excluded because L-citrulline and NOS2 levels were also increased in tumor mitochondria.
Keywords: non-small cell lung cancer, mitochondria, nitric oxide system, nitrosative stress, canonical and non-canonical NO production pathways, arginine.
For citation: Frantsiyants E.M., Bandovkina V.A., Kharagezov D.A., Neskubina I.V., Surikova E.I., Petrova Yu.A., Cheryarina N.D., Nashemukov T.R., Mamlina A.G. Indicators of the nitric oxide system in mitochondria of non-small cell lung cancer in men. Russian Medical Inquiry. 2026;10(9):707–713 (in Russ.). DOI: 10.32364/2587-6821-2026-10-9-15
About the authors:
Elena M. Frantsiyants — Dr. Sc. (Biol.), Professor, General Director General Advisor for Science, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0000-0003-3618-6890
Valeria A. Bandovkina — Dr. Sc. (Biol.), Assistant Professor, Head of the Laboratory for Study of Malignant Tumor Pathogenesis, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0000-0002-2302-8271
Dmitryi A. Kharagezov — C. Sc. (Med.), Head of the Department of Thoracic Surgery, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0000-0003-0640-2994
Irina V. Neskubina — Dr. Sc. (Biol.), Senior Scientific Officer, Laboratory for Study of Malignant Tumor Pathogenesis, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0000-0002-7395-3086
Ekaterina I. Surikova — C. Sc. (Biol.), Senior Scientific Officer, Laboratory for Study of Malignant Tumor Pathogenesis, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0000-0002-4318-7587
Yulia A. Petrova — C. Sc. (Biol.), Senior Scientific Officer, Laboratory for Study of Malignant Tumor Pathogenesis, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0000-0002-2674-9832
Natalia D. Cheryarina — Biologist, Laboratory for Study of Malignant Tumor Pathogenesis, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0000-0002-3711-8155
Tagir R. Nashemukov — 1st-Year Postgraduate Student, National Medical Research Centre for Oncology; 6, 14th Line str., Rostov-on-Don, 344037, Russian Federation; ORCID iD 0009-0008-6957-4893
Aleksandra G. Mamlina — Student, Rostov State Medical University; 29, Nakhichevanskyi lane, Rostov-on-Don, 344022, Russian Federation; ORCID iD 0009-0001-2153-535X
Contact information: Valeria A. Bandovkina, e-mail: valerryana@yandex.ru
Financial Disclosure: no authors have a financial or property interest in any material or method mentioned.
There is no conflict of interest.
Received 10.07.2026.
Revised 04.08.2026.
Accepted 27.08.2026.
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