[Structure-activity relationship of annonaceous acetogenins against multidrug resistant human hepatic carcinoma cell line SMMC-7721/ADR].

The present research was launched to investigate the effects of 12 annonaceous acetogenins (ACGs) on human hepatic carcinoma cell line SMMC-7721/ADR, and to find out their structure-activity relationship. SMMC-7721/ADR cells were treated with 12 ACGs including annosquamin A(1)，annosquamin B(2)，annotemoyin-1(3)，uvariamicin Ⅱ(4)，annosquacin D(5)，annosquacin B(6)，isodesacetyluvaricin(7)，uvarigrandin A(8)，squamostatin D(9)，squamostatin E(10)，squamostatin A(11)，and 12,15-cis-squamostatin A(12) for 24 h, and the different expression of the target gene NDUFV2 were detected by quantitative real-time PCR. All the tested compounds made the expression of the target gene NDUFV2 decreased on human hepatic carcinoma cell line SMMC-7721/ADR, of which the bistetrahydrofuran ACGs showed the best activity,which the non-adjacent bistetrahydrofuran ACGs displayed the worst activity.The ACGs with the reducing number of carbons between γ-unsaturated lactone and the close tetrahydrofuran (THF) ring are more potent. For bistetrahydrofuran ACGs with the same nucleus skeleton,they would be more active as more hydroxyls on aliphatic chain, which for the non-adjacent bistetrahydrofuran ACGs with less hydroxyls on aliphatic chain that would be more active. ACGs with 3 hydroxyls on aliphatic chain would be more active. ACGs with threo configuration are more active than erythro configurotion, and the compounds with cis THF ring seem to be superior to those of trans THF ring. Furthermore, the ACGs with the reducing number of carbons between terminal methyl and the close tetrahydrofuran (THF) ring are more potent.

Three new antitumor annonaceous acetogenins from the seeds of Annona squamosa.

Two new annonaceous acetogenins squamocin P (2) and annosquatin III (3) and one new ACG precursor dieporeticenin B (1) along with five known precursors (4-8) were isolated from the seeds of Annona squamosa. Their structures were ascertained by chemical methods and various spectral evidences. These compounds showed inhibitory effects against three multidrug-resistant (MDR) cancer cell lines. Compound 2 and 3 displayed selective cytotoxicity against SMMC 7721/T (IC50 0.435 and 1.79 µM) and MCF-7/ADR (IC50 values 3.34 and 4.04 µM).

Antitumor activity of Annona squamosa seed oil.

CONTEXT: Custard apple (Annona squamosa Linn.) is an edible tropical fruit, and its seeds have been used to treat "malignant sore" (cancer) and other usage as insecticide. A comparison of extraction processes, chemical composition analysis and antitumor activity of A. squamosa seed oil (ASO) were investigated. MATERIALS AND METHODS: The optimal extraction parameters of ASO were established by comparing percolation, soxhlet, ultrasonic and SFE-CO2 extraction methods. The chemical composition of fatty acid and content of total annonaceous acetogenins (ACGs) of ASO was investigated by GC-MS and colorimetric assay, and anti-tumor activity of ASO was tested using H22 xenografts bearing mice. RESULTS: The optimal extraction parameters of ASO were obtained as follows: using soxhlet extraction method with extraction solvent of petroleum ether, temperature of 80°C, and extraction time of 90min. Under these conditions, the yield of ASO was 22.65%. GC-MS analysis results showed that the main chemical compositions of fatty acid of ASO were palmitic acid (9.92%), linoleic acid (20.49%), oleic acid (56.50%) and stearic acid (9.14%). The total ACGs content in ASO was 41.00mg/g. ASO inhibited the growth of H22 tumor cells in mice with a maximum inhibitory rate of 53.54% by oral administration. Furthermore, it was found that ASO exerted an antitumor effect via decreasing interleukin-6 (IL-6), janus kinase (Jak) and phosphorylated signal transducers and activators of transcription (p-Stat3) expression. DISCUSSION AND CONCLUSION: The results demonstrated that ASO suppressed the H22 solid tumor development may due to its main chemical constituents unsaturated fatty acid and ACGs via IL-6/Jak/Stat3 pathway. ASO may be a potential candidate for the treatment of cancer.