Wentilactone B from Aspergillus wentii induces apoptosis and inhibits proliferation and migration of human hepatoma SMMC-7721 cells.

Wentilactone B (EN-48-57) is one of the six derivatives separated from Aspergillus wentii (EN-48). Of these derivatives, Wentilactone B exerted a more significant antibacterial and cytotoxic activity in several tumor cell lines. The present study demonstrates that Wentilactone B could efficiently induce SMMC-7721 cells apoptosis, but not normal hepatic cells, as measured by an inverted microscope, 4',6-diamidino-2-phenylindole staining and flow cytometry. In addition, Wentilactone B could inhibit the metastasis of SMMC-7721 cells, which was detected by colony formation, scratch migration and a transwell assay, and could induce a series of intracellular events, including the down-regulation of CD44 and epidermal growth factor receptor proteins. In conclusion, Wentilactone B inhibited the growth of SMMC-7721 cells by triggering apoptosis and inhibiting metastasis.

SD118-xanthocillin X (1), a novel marine agent extracted from Penicillium commune, induces autophagy through the inhibition of the MEK/ERK pathway.

A compound named SD118-xanthocillin X (1) (C(18)H(12)N(2)O(2)), isolated from Penicillium commune in a deep-sea sediment sample, has been shown to inhibit the growth of several cancer cell lines in vitro. In the present study, we employed a growth inhibition assay and apoptotic analysis to identify the biological effect and detailed mechanism of SD118-xanthocillin X (1) in human hepatocellular carcinoma (HepG2) cells. SD118-xanthocillin X (1) demonstrated a concentration-dependent inhibitory effect on the growth of HepG2 cells and caused slight cellular apoptosis and significantly induced autophagy. Autophagy was detected as early as 12 h by the conversion of microtubule-associated protein 1 light chain 3 (LC3-I) to LC3-II, following cleavage and lipid addition to LC3-I. The pharmacological autophagy inhibitor 3-methyladenine largely attenuates the growth inhibition and autophagic effect of SD118-xanthocillin X (1) in HepG2 cells. Our data also indicated that the autophagic effect of SD118-xanthocillin X (1) occurs via the down-regulation of the MEK/ERK signaling pathway and the up-regulated class III PI3K/Beclin 1 signaling pathway.

High expression of AKR1C1 is associated with proliferation and migration of small-cell lung cancer cells.

AKR1C1 is a member of the AKR1C family, which not only plays an important role in hormone metabolism but is believed to be involved in carcinogen metabolism. Our previous study demonstrated that AKR1C1 was highly expressed in lung tumor tissues as compared with the tumor-adjacent tissues. Small-cell lung cancer (SCLC) is a special type of lung cancer. Surgical treatment of SCLC is usually difficult due to the high degree of malignancy and early metastasis, and difficulty in obtaining clinical specimens. There is not much basic or clinical research on SCLC in the People's Republic of China even in recent years. To investigate the mechanism of AKR1C1 in the pathogenesis of SCLC, the present study used H446 cell line to see whether AKR1C1 could affect the proliferation or migration of SCLC cells, and used a lentivirus to build the AKR1C1 overexpression and under-expression cell lines. The results indicated that AKR1C1 was an important inducement in the proliferation and migration of H446 cells. AKR1C1 promoted cell proliferation and played a vital role in the migration of SCLC cells. These results were also verified in nude mice in vivo. In conclusion, AKR1C1 plays an important role in the development and progression of SCLC and may represent an independent biomarker for assessment of the primary prognosis and therapy of SCLC.