Planta Med 2014; 80 - P1N25
DOI: 10.1055/s-0034-1394615

Marine-derived fungi extracts increase doxorubicin's cytotoxic effect in lung cancer cells

A Ramos 1, M Moreira 1, B Castro-Carvalho 1, 2, M Prata-Sena 1, 2, T Dethoup 3, S Buttachon 1, 2, A Kijjoa 1, 2, E Rocha 1, 2
  • 1CIIMAR/CIMAR – Interdisciplinary Center for Marine and Environmental Research, University of Porto (U.Porto), Rua dos Bragas, 289, 4050 – 123, Porto, Portugal
  • 2ICBAS – Instituto de Ciências Biomédicas de Abel Salazar and CIIMAR, Universidade do Porto (U.Porto), Rua de Jorge Viterbo Ferreira, 228, 4050 – 313, Porto, Portugal
  • 3Department of Plant Pathology, Faculty of Agriculture, Kasetsart University, Bangkok, Thailand

Lung cancer accounts for 13% of all cancers worldwide [1], being doxorubicin (dox) one of the chemotherapeutic drugs in use, but with severe side effects [2]. However, drug combination with natural compounds may enhance treatment [3]. In this context, we wanted to evaluate the antitumor activity of extracts of three marine-derived fungi, Neosartorya tsunodae KUFC 9213 (E1), N. siamensis KUFA 0017 (E2) and N. laciniosa KUFC 7896 (E3), alone or combined with dox in lung carcinoma cell line (A549). Cells were incubated with fungal extracts (100 µg/ml) singly or mixed with dox (0.54µM) for 48h. Anti-proliferative effect was evaluated by MTT assay. Induction of DNA damage and apoptosis were evaluated by comet assay and nuclear condensation, respectively. The E1 and E3 extracts, alone, did not decrease cell proliferation, while E2 and dox decreased cell proliferation by 25% and 40%, respectively. When in combination with dox, the three fungal extracts significantly decreased cell proliferation between 60% and 70%. The extracts enhanced anti-proliferative effects of dox in A549 cells by a synergistic (E1 and E3) or additive effect (E2). To understand the antitumoral mechanisms, the ability to induce DNA damage and apoptosis were evaluated. E3 extract when combined with dox significantly increased DNA damage in A549 cells. Fungal extracts did not induce apoptosis, in opposition to dox that increased apoptosis in 8%. When combined, extracts and dox significantly increased apoptosis from 17% to 30%. In conclusion, we demonstrated that the fungal extracts potentiate the antitumor action of dox, inhibiting cell proliferation and inducing DNA damage and apoptosis in lung cancer cells. Activity at lower concentrations should be evaluated.

Acknowledgements: This work was partially funded by Project MARBIOTECH(NORTE-07 – 0124-FEDER-000047) co-financed by North Portugal Regional Operational Programme under National Strategic Reference Framework through European Regional Development Fund

Keywords: Marine-derived fungi extracts, Drug combination, Lung cancer cell line, Doxorubicin, Synergistic effect, Additive effect, Cytotoxic effect

References:

[1] Jemal A et al. (2011) CA-Cancer J Clin 61:69 – 90.

[2] Thorn C et al. (2011) Pharmacogenet Genomics 21:440 – 446.

[3] Abraham I et al. (2012) Mar Drugs 10:2312 – 2321.