Cytotoxic and Pro-Apoptotic Effects of Cassane Diterpenoids from the Seeds of Caesalpinia sappan in Cancer Cells

The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R‒T (1-3) and caesalsappanins M and N (4 and 5), together with seven known compounds 6-12. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute c...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2016-06, Vol.21 (6), p.791
Main Authors: Bao, Han, Zhang, Le-Le, Liu, Qian-Yu, Feng, Lu, Ye, Yang, Lu, Jin-Jian, Lin, Li-Gen
Format: Article
Language:English
Subjects:
Antineoplastic Agents, Phytogenic - chemistry
Antineoplastic Agents, Phytogenic - pharmacology
apoptosis
Apoptosis - drug effects
Biphenyl Compounds - chemistry
Biphenyl Compounds - pharmacology
Caesalpinia - chemistry
Caesalpinia sappan
cassane diterpenoids
Cell Proliferation - drug effects
cytotoxicity
Diterpenes - chemistry
Diterpenes - isolation & purification
Diterpenes - pharmacology
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Neoplasms - drug therapy
p53
Seeds - chemistry
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Summary:The chemical study on the seeds of Caesalpinia sappan led to the isolation of five new cassane diterpenoids, phanginins R‒T (1-3) and caesalsappanins M and N (4 and 5), together with seven known compounds 6-12. Their structures were elucidated on the basis of NMR and HRESIMS analyses. The absolute configurations of compounds 1 and 4 were determined by the corresponding CD spectra. All the isolated compounds were tested for their cytotoxicity against ovarian cancer A2780 and HEY, gastric cancer AGS, and non-small cell lung cancer A549 cells. Compound 1 displayed significant toxicity against the four cell lines with the IC50 values of 9.9 ± 1.6 µM, 12.2 ± 6.5 µM, 5.3 ± 1.9 µM, and 12.3 ± 3.1 µM, respectively. Compound 1 induced G1 phase cell cycle arrest in A2780 cells. Furthermore, compound 1 dose-dependently induced A2780 cells apoptosis as evidenced by Hoechst 33342 staining, Annexin V positive cells, the up-regulated cleaved-PARP and the enhanced Bax/Bcl-2 ratio. What's more, compound 1 also promoted the expression of the tumor suppressor p53 protein. These findings indicate that cassane diterpenoids might have potential as anti-cancer agents, and further in vivo animal studies and structural modification investigation are needed.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules21060791