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

ABSTRACT: 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.

SUBMITTER: Bao H

PROVIDER: S-EPMC6274183 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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

Bao Han H Zhang Le-Le LL Liu Qian-Yu QY Feng Lu L Ye Yang Y Lu Jin-Jian JJ Lin Li-Gen LG

Molecules (Basel, Switzerland) 20160618 6

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 A ...[more]

PMID: 27322234

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Project description:Ethnopharmacological relevanceCaesalpinia sappan is a common remedy in Traditional Chinese Medicine and possesses diverse biological activities including anti-inflammatory properties. Osteoarthritis (OA) is a degenerative joint disease with an inflammatory component that drives the degradation of cartilage extracellular matrix. In order to provide a scientific basis for the applicability of Caesalpinia sappan in arthritic diseases, the present study aimed to assess the effects of an ethanolic Caesalpinia sappan extract (CSE) on human chondrocytes and macrophages.Materials and methodsPrimary human chondrocytes were isolated from cartilage specimens of OA patients. Primary cells, SW1353 chondrocytes and THP-1 macrophages were serum-starved and pretreated with different concentrations of CSE prior to stimulation with 10 ng/ml of interleukin-1beta (IL-1?) or lipopolysaccharide (LPS). Following viability tests, nitric oxide (NO) and tumor necrosis factor-alpha (TNF-?) were evaluated by Griess assay and ELISA, respectively. Using validated real-time PCR assays, mRNA levels of IL-1?, TNF-?, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) were quantified. SW1353 cells were cotransfected with a COX-2 luciferase reporter plasmid and nuclear factor-kappa-B (NF-?B) p50 and p65 expression vectors in the presence or absence of CSE.ResultsCSE dose-dependently inhibited the expression of pro-inflammatory cytokines IL-1? and TNF-? in IL-1?-stimulated chondrocytes and LPS-stimulated THP-1 macrophages. CSE further suppressed the synthesis of NO in primary OA chondrocytes by blocking iNOS mRNA expression. The inhibition of COX-2 transcription was found to be related with the CSE inhibition of the p65/p50-driven transactivation of the COX-2 promoter.ConclusionsThe present report is first to demonstrate the anti-inflammatory activity of CSE in an in vitro cell model of joint inflammation. CSE can effectively abrogate the IL-1?-induced over-expression of inflammatory mediators at the transcriptional level in human chondrocytes and macrophages, most likely by inhibiting NF-?B (p65/p50) signaling. Blockade of IL-1?-induced NF-?B signaling and its downstream pro-inflammatory targets by CSE may be beneficial for reducing cartilage breakdown in arthritis.

Dataset Information

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

Publications

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

Similar Datasets

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