title: In vitro induction of apoptosis by isosclerone from marine-derived fungus Aspergillus fumigatus.
abstract: In the present study, we investigated the apoptotic effects of isosclerone from marine-derived fungi on human breast cancer MCF-7 cells. Treatment with isosclerone exhibited a characteristic feature of apoptosis including significant cytotoxicity and DNA fragmentation in cancer cells. In addition, The apoptosis induction abilities of the isosclerone was studied by analyzing the expression of caspase-3, -8 and -9, Bcl-2 family, NF-κ-B P50, P65, and IKK proteins. Western blot and RT-PCR analysis have indicated that isosclerone induce cancer cells apoptosis through down-regulated Bcl-2 family and up-regulated caspases, and activating the NF-κ-B signaling pathway. Our data demonstrate that isosclerone specifically binds to crystal structure of apoptosis regulator BCL-2 and pseudo-activated procaspase-3 proteins through down-regulated Bcl-2 family and up-regulated caspases, and activating the NF-κ-B signaling pathway. Our proof-of-principle study should have a positive impact on future drug discovery.
authors.affiliation: Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Yong-Xin
authors.initials: YX
authors.lastname: Li
authors.affiliation: Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Kyong-Hwa
authors.initials: KH
authors.lastname: Kang
authors.affiliation: Department of Chemistry, Pukyong National University, Busan 608-737, Republic of Korea.
authors.forename: Hak Jun
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Marine Bioprocess Research Center, Pukyong National University, Busan 608-737, Republic of Korea; Specialized Graduate School Science and Technology Convergence, Department of Marine Bio Convergence Science, Pukyong National University, Busan 608-737, Republic of Korea. Electronic address: sknkim@pknu.ac.kr.
authors.forename: Se-Kwon
authors.initials: SK
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001232:Aspergillus fumigatus / Q000737:chemistry*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D061986:MCF-7 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D009281:Naphthalenes; C000595804:isosclerone
keywords: Apoptosis; Bcl-2 family; Caspase-3, -8 and -9; Isosclerone; Small molecule docking