A lactose-binding lectin from the marine sponge Cinachyrella apion (Cal) induces cell death in human cervical adenocarcinoma cells.
Cancer represents a set of more than 100 diseases, including malignant tumors from different locations. Strategies inducing differentiation have had limited success in the treatment of established cancers. Marine sponges are a biological reservoir of bioactive molecules, especially lectins. Several animal and plant lectins were purified with antitumor activity, mitogenic, anti-inflammatory and antiviral, but there are few reports in the literature describing the mechanism of action of lectins purified from marine sponges to induce apoptosis in human tumor cells. In this work, a lectin purified from the marine sponge Cinachyrella apion (CaL) was evaluated with respect to its hemolytic, cytotoxic and antiproliferative properties, besides the ability to induce cell death in tumor cells. The antiproliferative activity of CaL was tested against HeLa, PC3 and 3T3 cell lines, with highest growth inhibition for HeLa, reducing cell growth at a dose dependent manner (0.5-10 µg/mL). Hemolytic activity and toxicity against peripheral blood cells were tested using the concentration of IC(50) (10 µg/mL) for both trials and twice the IC(50) for analysis in flow cytometry, indicating that CaL is not toxic to these cells. To assess the mechanism of cell death caused by CaL in HeLa cells, we performed flow cytometry and western blotting. Results showed that lectin probably induces cell death by apoptosis activation by pro-apoptotic protein Bax, promoting mitochondrial membrane permeabilization, cell cycle arrest in S phase and acting as both dependent and/or independent of caspases pathway. These results indicate the potential of CaL in studies of medicine for treating cancer.
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Luciana
L
Rabelo
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Norberto
N
Monteiro
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Raphael
R
Serquiz
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Paula
P
Santos
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Ruth
R
Oliveira
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Adeliana
A
Oliveira
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Hugo
0000-0003-2252-1221
H
Rocha
Department of Nutrition, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Ana Heloneida
AH
Morais
Department of Cellular Biology and Genetic, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Adriana
0000-0002-3822-6502
A
Uchoa
Department of Biochemistry, Federal University of Rio Grande do Norte, Natal, RN, 59072-970, Brazil.
Elizeu
E
Santos
D016475:3T3 Cells; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D006367:HeLa Cells; D053878:Hemolytic Agents / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007785:Lactose / Q000378:metabolism*; D037102:Lectins / Q000302:isolation & purification / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis / Q000188:drug therapy / Q000378:metabolism; D011161:Porifera / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D053878:Hemolytic Agents; D037102:Lectins; D051028:bcl-2-Associated X Protein; D020169:Caspases; D007785:Lactose