Northeast Biotechnology Network (RENORBIO), Postgraduate Program in Biotechnology, Federal University of Piauí - UFPI, Teresina, Piauí, 64.049-550, Brazil.
Nucleus of Applied Research to Sciences (NIAC), Federal Institute of Education, Science and Technology of Maranhão (IFMA), Timon, Maranhão, 65.635-468, Brazil.
Cell Mol Biol (Noisy-le-grand). 2020 Jun 25;66(4):120-126.
Citrinin (CIT) is a cytotoxic, hepatotoxic, nephrotoxic and cardiotoxic metabolite obtained from Penicillium citrinum, that has been increasingly searched as an anticancer drug candidate. In this study, we assessed the antitumor effects of citrinin, using cytogenetic biomarkers for genotoxicity in Sarcoma 180 (S-180) ascitic fluid cells of mice. Citrinin, extracted from P. citrinum acetonitrile extract, was characterized by LC-MS. Cytotoxic assessment was done through using comet (alkaline version) and micronucleus assays. In S-180 cells, CI50 of CIT was 3.77 μg/mL, while at 12.5 and 100 μg/mL, CIT was as cytotoxic as doxorubicin (2 μg/mL). At 0.5, 1.0 and 2.0 μg/mL, it induced genotoxicity and mutagenicity in S-180 cells, especially at 2 μg/mL, triggering oxidative damage similar to hydrogen peroxide (10 mM). The antitumor effects were evidenced by a marked increase in S-180 cells apoptosis and necrosis due to clastogenic and/or aneugenic cytogenetic effects (micronucleus formation), as well as by induction of nucleoplasm bridges and nuclear buds, culminating in S-180 apoptosis and necrosis. CIT has potential as drug candidate for antitumor purposesbyinvolving cytogenetic mechanisms.
桔青霉素（CIT）是一种细胞毒性、肝毒性、肾毒性和心脏毒性代谢物，来源于桔青霉，作为一种抗癌药物候选物，它已被越来越多地研究。在这项研究中，我们使用细胞遗传学生物标志物评估了桔青霉素对小鼠肉瘤 180（S-180）腹水细胞的遗传毒性，以评估其抗肿瘤作用。桔青霉素从桔青霉乙腈提取物中提取，并用 LC-MS 进行了表征。通过使用彗星（碱性）和微核试验进行了细胞毒性评估。在 S-180 细胞中，CIT 的 CI50 为 3.77μg/mL，而在 12.5 和 100μg/mL 时，CIT 的细胞毒性与阿霉素（2μg/mL）相当。在 0.5、1.0 和 2.0μg/mL 时，它在 S-180 细胞中诱导遗传毒性和致突变性，尤其是在 2μg/mL 时，引发类似于过氧化氢（10mM）的氧化损伤。抗肿瘤作用的证据是由于桔青霉素的染色体断裂和/或非整倍体遗传毒性作用（微核形成），导致 S-180 细胞凋亡和坏死的明显增加，以及核质桥和核芽的诱导，最终导致 S-180 细胞凋亡和坏死。CIT 通过涉及细胞遗传学机制，有作为抗肿瘤药物候选物的潜力。
