Evaluation of In Vitro Cytotoxic Potential of Avarol towards Human Cancer Cell Lines and In Vivo Antitumor Activity in Solid Tumor Models

  • Molecules. 2022 Dec 19;27(24):9048. doi: 10.3390/molecules27249048.
Tatjana P Stanojkovic  1 Marina Filimonova  2 Nadja Grozdanic  1 Slavica Petovic  3 Anna Shitova  2 Olga Soldatova  2 Alexander Filimonov  2 Jelena Vladic  4 Petr Shegay  5 Andrey Kaprin  5  6 Sergey Ivanov  2 Marina Nikitovic  1  7
Affiliations
  • 1. Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, 11000 Belgrade, Serbia.
  • 2. A. Tsyb Medical Radiological Research Center, Federal State Budget Institution National Medical Research Radiological Center of the Ministry of Healthcare of the Russian Federation, 249031 Obninsk, Russia.
  • 3. Institute of Marine Biology, University of Montenegro, 85330 Kotor, Montenegro.
  • 4. Faculty of Technology, University of Novi Sad, 21000 Novi Sad, Serbia.
  • 5. National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, 249030 Obninsk, Russia.
  • 6. Peoples' Friendship University of Russia, Medical Institute (RUDN University), 117198 Moscow, Russia.
  • 7. Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia.
Abstract

The goal of this study was to determine the activity in vitro and in vivo of avarol, a sesquiterpene hydroquinone originating from the Dysidea avara Sponge from the south Adriatic Sea, against different Cancer cell lines and two types of mouse carcinoma. To investigate the in vitro cytotoxicity, a human cervix adenocarcinoma cell line (HeLa), human colon adenocarcinoma (LS174), human non-small-cell lung carcinoma (A549), and a normal human fetal lung fibroblast cell line (MRC-5) were used. The in vivo antitumor activity was investigated against two transplantable mouse tumors, the Ehrlich carcinoma (EC) and cervical Cancer (CC-5). The effect of avarol on Cancer cell survival, which was determined by the microculture tetrazolium test, confirmed a significant in vitro potency of avarol against the investigated cell lines, without selectivity towards MRC-5. The highest cytotoxicity was exhibited against HeLa Cancer cells (10.22 ± 0.28 μg/mL). Moreover, potent antitumor activity against two tumor models was determined, as the intraperitoneal administration of avarol at a dose of 50 mg/kg resulted in a significant inhibition of tumor growth in mice. After three administrations of avarol, a 29% inhibition of the EC growth was achieved, while in the case of CC-5, a 36% inhibition of the tumor growth was achieved after the second administration of avarol. Therefore, the results indicate that this marine sesquiterpenoid hydroquinone could be a promising bioactive compound in the development of new Anticancer medicine.

Keywords
Dysidea avara; Ehrlich carcinoma; avarol; cervical cancer; cytotoxicity.
Products