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Xerophilusin B induces cell cycle arrest and apoptosis in esophageal squamous cell carcinoma cells and does not cause toxicity in nude mice.
- Source :
-
Journal of natural products [J Nat Prod] 2015 Jan 23; Vol. 78 (1), pp. 10-6. Date of Electronic Publication: 2015 Jan 02. - Publication Year :
- 2015
-
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.
- Subjects :
- Animals
Antineoplastic Agents, Phytogenic pharmacology
Apoptosis drug effects
Blotting, Western
Caspase 3 metabolism
Caspase 9 metabolism
Diterpenes chemistry
Diterpenes isolation & purification
Diterpenes, Kaurane chemistry
Diterpenes, Kaurane isolation & purification
Esophageal Squamous Cell Carcinoma
Female
Humans
Mice
Mice, Inbred BALB C
Mice, Nude
Molecular Structure
Carcinoma, Squamous Cell drug therapy
Diterpenes pharmacology
Diterpenes, Kaurane pharmacology
Esophageal Neoplasms drug therapy
G2 Phase Cell Cycle Checkpoints drug effects
Isodon chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6025
- Volume :
- 78
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of natural products
- Publication Type :
- Academic Journal
- Accession number :
- 25555195
- Full Text :
- https://doi.org/10.1021/np500429w