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.
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Authors | Ran Yao, Zhaoli Chen, Chengcheng Zhou, Mei Luo, Xuejiao Shi, Jiagen Li, Yibo Gao, Fang Zhou, Jianxin Pu, Handong Sun, Jie He |
Journal | Journal of natural products
(J Nat Prod)
Vol. 78
Issue 1
Pg. 10-6
(Jan 23 2015)
ISSN: 1520-6025 [Electronic] United States |
PMID | 25555195
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Diterpenes
- Diterpenes, Kaurane
- xerophilusin B
- Caspase 3
- Caspase 9
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects)
- Blotting, Western
- Carcinoma, Squamous Cell
(drug therapy)
- Caspase 3
(metabolism)
- Caspase 9
(metabolism)
- Diterpenes
(chemistry, isolation & purification, pharmacology)
- Diterpenes, Kaurane
(chemistry, isolation & purification, pharmacology)
- Esophageal Neoplasms
(drug therapy)
- Esophageal Squamous Cell Carcinoma
- Female
- G2 Phase Cell Cycle Checkpoints
(drug effects)
- Humans
- Isodon
(chemistry)
- Mice
- Mice, Inbred BALB C
- Mice, Nude
- Molecular Structure
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