Secondary metabolites from actinomycetes especially the genus Streptomyces may be one of the most important sources for novel anticancer agents. A purified fraction from a novel actinomycete strain, Streptomyces sp. H7372, was elucidated in breast cancer cells. We have isolated three purified fractions from a novel strain, Streptomyces sp. H7372. One of the fractions, designated as 31-2, exhibited the strongest growth-inhibitory effect and thereby was selected for further studies. 31-2 exerted a growth-inhibitory effect on a panel of 15 human cancer and 2 non-malignant cell lines. In MCF-7 and MDA-MB-231 breast cancer cells, 31-2 induced a cytostatic (anti-proliferative) effect without causing cytotoxicity (cell death). Our data suggest that the cytostasis resulted from cell cycle arrest at the G1 phase in MCF-7 cells and at the S phase in MDA-MB-231 cells. Western blot analysis demonstrated a modulation of phosphorylation of the Rb and CDC2 proteins and of CDK4, cyclin D1 and cyclin D3 in the 31-2-treated breast cancer cell lines. The protein levels of CDK2, CDK6, and PCNA were not affected by 31-2 treatment. 31-2 also exhibited an anti-invasive effect in MDA-MB-231 cells. However, this effect is not attributed to the modulation of proteolytic activity in MDA-MB-231 cells as the enzymatic degradation of type IV collagen was not affected by 31-2. The 31-2 is a potent cytostatic and anti-invasive agent and modulates the cell cycle pathway. Together, these results will have important implications in searching for novel approaches to treat cancer.
Phytochemical investigations of the twig and leaf extracts of Goniothalamus tortilipetalus resulted in the isolation and identification of two new alkaloids, goniotortiline (1) and goniotortilactam (2), three new styryl lactone derivatives, goniotortilactone (3) and goniotortilols A (4) and B (5), and 25 known compounds. Their structures were elucidated by spectroscopic methods and HRESITOFMS data. Compounds 5, 13, 15, 16, 22, and 30 inhibited nitric oxide (NO) production with IC50 values ranging from 8.7 ± 0.1 to 17 ± 1 μM, revealing stronger effects than the standard drug, dexamethasone (IC50 16.9 ± 2.2 μM), and compound 30 possessed the most potent NO production inhibition. Compounds 12 and 29 demonstrated notable efficacy in enhancing glucose consumption with IC50 values of 77 ± 4 and 66 ± 4 μM, respectively, while their glucose uptakes were 1.7- and 2-fold, respectively.