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.

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.

MeSH terms

  • Adenocarcinoma*
  • Animals
  • Antineoplastic Agents* / pharmacology
  • Carcinoma, Non-Small-Cell Lung*
  • Cell Line
  • Colonic Neoplasms*
  • Humans
  • Hydroquinones
  • Lung Neoplasms*
  • Mice
  • Sesquiterpenes* / pharmacology

Substances

  • avarol
  • hydroquinone
  • Hydroquinones
  • Antineoplastic Agents
  • Sesquiterpenes

Grants and funding

The authors are thankful to the Ministry of Education, Science, and Technological Development of the Republic of Serbia (grant number: 451-03-68/2022-14/200043) and the Ministry of Science of the Republic of Montenegro as well as the Ministry of Health of the Russian Federation, the Russian Foundation for Basic Research, and the Kaluga Region (grant number: 16-44-400256) for financial support.