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Acetonic extracts of the endolichenic fungus EL002332 isolated from Endocarpon pusillum exhibits anticancer activity in human gastric cancer cells
- Acetonic extracts of the endolichenic fungus EL002332 isolated from Endocarpon pusillum exhibits anticancer activity in human gastric cancer cells
- Yang, Yi; Bae, Woo Kyun; Nam, Sang-Jip; Jeong, Min-Hye; Zhou, Rui; Park, So-Yeon; Tas, Isa; Hwang, Yun-Ho; Park, Myong-Suk; Chung, Ik Joo; Kim, Kyung Keun; Hur, Jae-Seoun; Kim, Hangun
- Ewha Authors
- SCOPUS Author ID
- Issue Date
- Journal Title
- PHYTOMEDICINE vol. 40, pp. 106 - 115
- Anticancer; Tumorigenicity; Viability; Motility; Lichen; Endolichenic fungi
- ELSEVIER GMBH, URBAN &
- SCIE; SCOPUS
- Document Type
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- Background: Endolichenic fungi are microbes that inhabit the thalli of lichens and produce various unique chemicals that can be used for pharmaceutical purposes. Purpose: This study screened a library of endolichenic fungal extracts to identify novel anticancer agents capable of suppressing the tumorigenicity of human cancer cells. Methods: Active compounds were isolated from extracts of endolichenic fungi by column chromatography and reverse-phase HPLC. The anticancer effects of the extracts on cell viability was assessed with the use of MTT assay, Western blotting, fluorescence labeling of apoptotic cell, and flow cytometric analysis; and cell motility with the use of migration, invasion and soft agar colony-formation assay in vitro; and on skin and intraperitoneal mouse xenograft tumors in vivo were investigated. The therapeutic effects of the extract alone or in combination with the conventional chemoreagent docetaxel were analyzed by sulforhodamine B assay. Results: Acetone extracts of EL002332, isolated from Endocarpon pusillum collected in the China desert in 2010, showed selective cytotoxicity against AGS human gastric cancer cells and CT26 mouse colon cancer cells. An active pure compound named myC was isolated from mycelium acetone extracts in a liquid culture system and showed more potent cytotoxicity than crude extracts in the AGS cell line. Especially, myC greatly increased the apoptotic cell population at the IC50 concentration and activated apoptotic signaling by regulating Bcl2 family protein expression and caspase pathway activity. EL002332 crude extracts and myC decreased AGS cell motility at sub-lethal concentrations. In vivo skin and intraperitoneal xenograft tumor experiments showed that the size of tumors and the tumor score were significantly smaller in EL002332 crude extract-treated groups than in control groups. EL002332 crude extracts showed synergistic effects with docetaxel on the AGS and TMK1 cell lines. Conclusion: The endolichenic fungus EL002332 has potential anticancer activity in gastric cancer and peritoneal carcinomatosis.
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