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交链格孢(SDHY01/02),一种与 Lamellodysidea herbacea 相关的真菌:其抗癌潜力及其活性成分。

Alternaria alternata (SDHY01/02), a fungus associated with Lamellodysidea herbacea: its anticancer potential and responsible constituent(s).

机构信息

Fermentation and Microbial Biotechnology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, 180001, India.

Academy of Scientific and Innovative Research (AcSIR), CSIR-HRD Centre Campus, Ghaziabad, 201002, India.

出版信息

Int Microbiol. 2023 Nov;26(4):1143-1155. doi: 10.1007/s10123-023-00368-8. Epub 2023 May 5.

Abstract

One of the biggest global causes of death is cancer. The side effects of currently available therapies have triggered the search for new drugs. The marine environment, with its vast biodiversity, including sponges, is a rich source of natural products with immense pharmaceutical potential. The aim of the study was to analyze the microbes associated with the marine sponge, Lamellodysidea herbacea, and explore them as resources for anticancer ability. This study includes the isolation of fungi from L. herbacea, and their evaluation for cytotoxic potential against human cancer cell lines such as A-549 (lung), HCT-116 (colorectal carcinoma), HT-1080 (Fibrosarcoma), and PC-3 (prostate) using MTT assay. This revealed that fifteen extracts showed significant anticancer ability (IC ≤ 20 µg/mL), at least against one of the cell lines. Three extracts, SPG12, SPG19, and SDHY 01/02, were found significant in terms of anticancer activity, at least against three to four cell lines (IC values ≤ 20 µg/mL). The fungus SDHY01/02 was identified by sequencing the internal transcribed spacer (ITS) region as Alternaria alternata. Its extract showed IC values < 10 µg/mL against all the tested cell lines and was further analysed through light and fluorescence microscopy. The extract of SDHY01/02 was active (lowest IC 4.27 µg/mL) against A549 cells in a dose-dependent manner and caused apoptotic cell death. Further, the extract was fractionated and analyzed the constituents by GC-MS (Gas Chromatography-Mass Spectrometry). Di-ethyl ether fraction revealed the constituents (having anticancer activity) such pyrrolo[1,2-a] pyrazine-1,4-dione, hexahydro-3-(2-methyl propyl); 4,5,6,7-tetrahydro-benzo[C]rhiophene-1-carboxylic acid cyclopropylamide; 17-pentatriacontene; 9,12-octadecadienoic acid (Z, Z)-, methyl ester; while DCM fraction contained Oleic acid, eicosyl ester. This is the first report of A. alternata with anticancer potential that has been isolated from the sponge L. herbacea, as far as we are aware.This A. alternata can be exploited to get anticancer molecule(s) in the future.

摘要

癌症是全球最大的死亡原因之一。目前可用疗法的副作用促使人们寻找新的药物。海洋环境拥有丰富的生物多样性,包括海绵,是具有巨大药物潜力的天然产物的丰富来源。本研究的目的是分析与海洋海绵 Lamellodysidea herbacea 相关的微生物,并将其作为抗癌能力的资源进行探索。本研究包括从 L. herbacea 中分离真菌,并使用 MTT 测定法评估它们对人癌细胞系(如 A-549(肺)、HCT-116(结直肠癌)、HT-1080(纤维肉瘤)和 PC-3(前列腺))的细胞毒性潜力。这表明,十五种提取物具有显著的抗癌能力(IC ≤ 20 µg/mL),至少对一种细胞系有作用。三种提取物 SPG12、SPG19 和 SDHY 01/02 在抗癌活性方面表现出显著作用,至少对三到四种细胞系(IC 值 ≤ 20 µg/mL)有作用。通过测序内部转录间隔区(ITS)区域,真菌 SDHY01/02 被鉴定为Alternaria alternata。其提取物对所有测试的细胞系的 IC 值均<10 µg/mL,并用荧光显微镜进一步分析。提取物 SDHY01/02 对 A549 细胞具有活性(最低 IC 4.27 µg/mL),呈剂量依赖性,并导致细胞凋亡。此外,提取物被分馏并通过 GC-MS(气相色谱-质谱)分析成分。二乙醚部分揭示了具有抗癌活性的成分,如吡咯并[1,2-a]吡嗪-1,4-二酮、六氢-3-(2-甲基丙基);4,5,6,7-四氢苯并[c]吡咯-1-羧酸环丙基酰胺;17-三十五烯;9,12-十八碳二烯酸(Z,Z)-,甲酯;而 DCM 部分含有油酸,二十烷基酯。据我们所知,这是首次从海绵 Lamellodysidea herbacea 中分离出具有抗癌潜力的 Alternaria alternata 的报道。这种 Alternaria alternata 将来可以用来获得抗癌分子。

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