Machado Kátia da Conceição, Sousa Lívia Queiroz de, Lima Daisy Jereissati Barbosa, Soares Bruno Marques, Cavalcanti Bruno Coêlho, Maranhão Sarah Sant'Anna, Noronha Janaina da Costa de, Rodrigues Domingos de Jesus, Militão Gardenia Carmen Gadelha, Chaves Mariana Helena, Vieira-Júnior Gerardo Magela, Pessoa Cláudia, Moraes Manoel Odorico de, Sousa João Marcelo de Castro E, Melo-Cavalcante Ana Amélia de Carvalho, Ferreira Paulo Michel Pinheiro
Postgraduate Program in Pharmaceutical Sciences, Federal University of Piauí, Teresina, Brazil.
Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Brazil.
Toxicol Lett. 2018 Mar 15;285:121-131. doi: 10.1016/j.toxlet.2017.12.018. Epub 2017 Dec 26.
Skin toad secretion present physiologically active molecules to protect them against microorganisms, predators and infections. This work detailed the antiproliferative action of marinobufagin on tumor and normal lines, investigate its mechanism on HL-60 leukemia cells and its toxic effects on Allium cepa meristematic cells. Initially, cytotoxic action was assessed by colorimetric assays. Next, HL-60 cells were analyzed by morphological and flow cytometry techniques and growing A. cepa roots were examined after 72 h exposure. Marinobufagin presented high antiproliferative action against all human tumor lines [IC values ranging from 0.15 (leukemia) to 7.35 (larynx) μM] and it failed against human erythrocytes and murine lines. Human normal peripheral blood mononuclear cells (PBMC) were up to 72.5-fold less sensitive [IC 10.88 μM] to marinobufagin than HL-60 line, but DNA strand breaks were no detected. Leukemia treaded cells exhibited cell viability reduction, DNA fragmentation, phosphatidylserine externalization, binucleation, nuclear condensation and cytoplasmic vacuoles. Marinobufagin also reduced the growth of A. cepa roots (EC: 7.5 μM) and mitotic index, caused cell cycle arrest and chromosomal alterations (micronuclei, delays and C-metaphases) in meristematic cells. So, to find out partially targeted natural molecules on human leukemia cells, like marinobufagin, is an amazing and stimulating way to continue the battle against cancer.
蟾蜍皮肤分泌物含有生理活性分子,可保护它们免受微生物、捕食者和感染。这项工作详细阐述了海蟾蜍精对肿瘤细胞系和正常细胞系的抗增殖作用,研究了其对HL-60白血病细胞的作用机制及其对洋葱根尖分生细胞的毒性作用。最初,通过比色法评估细胞毒性作用。接下来,通过形态学和流式细胞术技术分析HL-60细胞,并在暴露72小时后检查生长中的洋葱根尖。海蟾蜍精对所有人类肿瘤细胞系均表现出高抗增殖作用[IC值范围为0.15(白血病)至7.35(喉癌)μM],而对人类红细胞和鼠细胞系无效。人类正常外周血单核细胞(PBMC)对海蟾蜍精的敏感性比HL-60细胞系低72.5倍[IC 10.88μM],但未检测到DNA链断裂。白血病处理后的细胞表现出细胞活力降低、DNA片段化、磷脂酰丝氨酸外化、双核化、核浓缩和细胞质空泡化。海蟾蜍精还降低了洋葱根尖的生长(EC:7.5μM)和有丝分裂指数,导致分生细胞的细胞周期停滞和染色体改变(微核、延迟和C-中期)。因此,寻找像海蟾蜍精这样对人类白血病细胞有部分靶向作用的天然分子,是继续抗癌斗争的一种令人惊奇且振奋人心的方式。