title: Xerophilusin B induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma cells and does not cause toxicity in nude mice.
abstract: Esophageal cancer is the eighth most common cancer in the world and ranks as the sixth leading cause of cancer-related mortality. Esophageal cancer has a poor prognosis partially due to its low sensitivity to chemotherapy agents, and the development of new therapeutic agents is urgently needed. Here, the antitumor activity of a natural ent-kaurane diterpenoid, xerophilusin B (1), which was isolated from Isodon xerophilus, a perennial herb frequently used in Chinese folk medicine for tumor treatment, was investigated. Compound 1 exhibited antiproliferative effects against esophageal squamous cell carcinoma (ESCC) cell lines in a time- and dose-dependent manner with lower toxicity against normal human and murine cell lines. In vivo studies demonstrated that 1 inhibited tumor growth of a human esophageal tumor xenograft in BALB/c nude mice without significant secondary adverse effects, indicating its safety in treating ESCC. Furthermore, 1 induced G2/M cell cycle arrest and promoted apoptosis through mitochondrial cytochrome c-dependent activation of the caspase-9 and caspase-3 cascade pathway in ESCC cell lines. In conclusion, the observations herein reported showed that 1 is a potential chemotherapeutic agent for ESCC and merits further preclinical and clinical investigation for cancer drug development.
authors.affiliation: Department of Thoracic Surgery, Cancer Institute and Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences , Beijing 100021, People's Republic of China.
authors.forename: Ran
authors.initials: R
authors.lastname: Yao
authors.forename: Zhaoli
authors.initials: Z
authors.lastname: Chen
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhou
authors.forename: Mei
authors.initials: M
authors.lastname: Luo
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Shi
authors.forename: Jiagen
authors.initials: J
authors.lastname: Li
authors.forename: Yibo
authors.initials: Y
authors.lastname: Gao
authors.forename: Fang
authors.initials: F
authors.lastname: Zhou
authors.forename: Jianxin
authors.initials: J
authors.lastname: Pu
authors.forename: Handong
authors.initials: H
authors.lastname: Sun
authors.forename: Jie
authors.initials: J
authors.lastname: He
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D045786:Diterpenes, Kaurane / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D006801:Humans; D037602:Isodon / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015394:Molecular Structure
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004224:Diterpenes; D045786:Diterpenes, Kaurane; C410911:xerophilusin B; D053148:Caspase 3; D053453:Caspase 9