title: The marine metabolite SZ-685C induces apoptosis in primary human nonfunctioning pituitary adenoma cells by inhibition of the Akt pathway in vitro.
abstract: Nonfunctioning pituitary adenoma (NFPA) is one of the most common types of pituitary adenoma. The marine anthraquinone derivative SZ-685C has been isolated from the secondary metabolites of the mangrove endophytic fungus Halorosellinia sp. (No. 1403) which is found in the South China Sea. Recent research has shown that SZ-685C possesses anticancer and tumor suppressive effects. The tetrazolium-based colorimetric assay (MTT assay) to investigate the different effect of the marine compound SZ-685C on the proliferation of primary human NFPA cells, rat normal pituitary cells (RPCs) and rat prolactinoma MMQ cell lines. Hoechst 33342 dye/propidium iodide (PI) double staining and fluorescein isothiocyanate-conjugated Annexin V/PI (Annexin V-FITC/PI) apoptosis assays detected an enhanced rate of apoptosis in cells treated with SZ-685C. Enhanced expression levels of caspase 3 and phosphate and tensin homolog (PTEN) were determined by Western blotting. Notably, the protein expression levels of Akt were decreased when the primary human NFPA cells were treated with SZ-685C. Here, we show that SZ-685C induces apoptosis of human NFPA cells through inhibition of the Akt pathway in vitro. The understanding of apoptosis has provided the basis for novel targeted therapies that can induce death in cancer cells or sensitize them to established cytotoxic agents and radiation therapy.
authors: Department of Histology and Embryology, Medical school of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. wangx357@mail2.sysu.edu.cn.|Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. wangx357@mail2.sysu.edu.cn.|Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. wangx357@mail2.sysu.edu.cn.
authors: Xin
authors: X
authors: Wang
authors: Department of Histology and Embryology, Medical school of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. tanting395395@sina.com.|Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. tanting395395@sina.com.
authors: Ting
authors: T
authors: Tan
authors: Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. mmh222111@aliyun.com.
authors: Zhi-Gang
authors: ZG
authors: Mao
authors: Department of Histology and Embryology, Medical school of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. leini@mail2.sysu.edu.cn.|Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. leini@mail2.sysu.edu.cn.
authors: Ni
authors: N
authors: Lei
authors: Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. wzmyan@gmail.com.
authors: Zong-Ming
authors: ZM
authors: Wang
authors: Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. 13512725071@163.com.
authors: Bin
authors: B
authors: Hu
authors: Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. chenzhiyong111@126.com.
authors: Zhi-Yong
authors: ZY
authors: Chen
authors: Department of Histology and Embryology, Medical school of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. cesshzhg@mail.sysu.edu.cn.|Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. cesshzhg@mail.sysu.edu.cn.
authors: Zhi-Gang
authors: ZG
authors: She
authors: Department of Histology and Embryology, Medical school of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. zhuyongh@mail.sysu.edu.cn.|Key Laboratory of Functional Molecules from Marine Microorganisms, Department of Education of Guangdong Province, Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. zhuyongh@mail.sysu.edu.cn.
authors: Yong-Hong
authors: YH
authors: Zhu
authors: Department of Neurosurgery and Pituitary Tumour Center, The First Affiliated Hospital of Sun Yat-sen University, No.74, Zhongshan Road 2, Guangzhou 510080, China. wanghaij@mail.sysu.edu.cn.
authors: Hai-Jun
authors: HJ
authors: Wang
mesh_terms: D000236:Adenoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D000880:Anthraquinones / Q000302:isolation & purification / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001203:Ascomycota / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002681:China; D006801:Humans; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015175:Prolactinoma / Q000188:drug therapy / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors; D051381:Rats; D064210:Secondary Metabolism
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; C569938:SZ 685C; D051057:Proto-Oncogene Proteins c-akt