Activation of Apoptosis and Autophagy by Gratiola Officinalis Extract in Human Tumor Cell Lines

Natal’ya V. Polukonova
Saratov State Medical University named after V. I. Razumovsky, Russian Federation

Maria A. Baryshnikova
National Medical Research Center of Oncology named after N. N. Blokhin, Moscow, Russian Federation

Dmitry A. Khochankov
National Medical Research Center of Oncology named after N. N. Blokhin, Moscow, Russian Federation

Evgeniya V. Stepanova
National Medical Research Center of Oncology named after N. N. Blokhin, Moscow, Russian Federation

Eliso S. Solomko
National Medical Research Center of Oncology named after N. N. Blokhin, Moscow, Russian Federation

Anna V. Polukonova
Saratov State Medical University named after V. I. Razumovsky, Russian Federation

Dmitrij A. Mudrak
Saratov State Medical University named after V. I. Razumovsky, Russian Federation

Artem M. Mylnikov
Saratov State Medical University named after V. I. Razumovsky, Russian Federation

Alla B. Bucharskaya
Saratov State Medical University named after V. I. Razumovsky, Russian Federation

Galina N. Maslyakova
Saratov State Medical University named after V. I. Razumovsky, Russian Federation

Nikita A. Navolokin orcid (Login required)
Saratov State Medical University named after V. I. Razumovsky, Russian Federation


Paper #3449 received 1 Aug 2021; revised manuscript received 7 Oct 2021; accepted for publication 11 Oct 2021; published online 10 Nov 2021.

DOI: 10.18287/JBPE21.07.040307

Abstract

The problem of creating antitumor drugs with new mechanisms of action that predominantly induce apoptosis is still topical. The extract of Gratiola officinalis is a potential antitumor agent containing mainly flavonoids. The aim of this research is to study the effects of Gratiola officinalis extract on activation of apoptosis and autophagy in breast adenocarcinoma SK-BR-3 and kidney carcinoma A-498 lines. Apoptotic activity of the extract was studied by flow cytofluorometry using Hoechst stain and double staining with annexin V plus propidium iodide. There was 96.3% of cells in SK-BR-3 culture in late apoptosis phase detected by flow cytofluorometry method at the extract concentration of 0.88 mg/ml, 86.3% of cells were in apoptosis by Hoechst stain. The concentration of 0.82 mg/ml caused apoptosis in half of the cells. The extract has cytoprotective activity at low concentration (0.0352 mg/ml). The cytoprotection mechanism is realized through the activation of autophagy. The maximum number of autophagosomes in kidney carcinoma cells is observed at the extract concentration of 0.056 mg/ml. Thus, Gratiola officinalisextract is able to block cytoprotective autophagy with increasing the extract concentration and to activate apoptosis in 85% of tumor cells. Detailed research should be continued to understand the mechanisms of antitumor activity of Gratiola officinalisextract.

Keywords

autophagy; apoptosis; antitumor agents; Gratiola officinalis; antitumor agents; tumor; flavonoids

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