Identification and bioactivity evaluation of miliusanes from Miliusa sinensis.

Miliusanes are a class of anticancer lead molecules belonging to meroterpenoids with an 18-carbon skeleton isolated from Miliusa plants. A phytochemical study of the plant M. sinensis was carried out to discover new miliusanes with diverse structural features in order to better understand their structure-activity relationship. As a result, 20 compounds including 12 new ones (7-14 and 17-20) belonging to two sub-classes of miliusanes were isolated and identified from the twigs and leaves of this plant. Their structures, including absolute configurations, were determined by spectroscopic analyses and electronic circular dichroism. The absolute stereochemistry of miliusane structures has also been confirmed for the first time through the single crystal X-ray diffraction analysis of miliusol (1). Bioactivity evaluation showed that some of the miliusane isolates potently inhibit cell growth of several human derived cancer cell lines with IC50 values ranging from 0.52 to 23.5 µM. Compound 11 demonstrated more potent cytotoxic activity than the known miliusol (1) in stomach cancer cells though its structure contains an unconjugated 1, 4-diketone system, which added a new structure-activity feature to miliusanes. The preliminary mechanism of action studies revealed that they could be a class of dual cell migration inhibitor and senescence inducer.

Near-infrared AIE-active phosphorescent iridium(III) complex for mitochondria-targeted photodynamic therapy.

Mitochondria-targeted photodynamic therapy (PDT) has recently been recognized as a promising strategy for effective cancer treatment. In this work, a mitochondria-targeted near-infrared (NIR) aggregation-induced emission (AIE)-active phosphorescent Ir(III) complex (Ir1) is reported with highly favourable mitochondria-targeted bioimaging and cancer PDT properties. Complex Ir1 has strong absorption in the visible light region (∼500 nm) and can effectively produce singlet oxygen (1O2) under green light (525 nm) irradiation. It preferentially accumulates in the mitochondria of human breast cancer MDA-MB-231 cells as revealed by colocalization analysis. Complex Ir1 displays high phototoxicity toward human breast cancer MDA-MB-231 cells and mouse breast cancer 4T1 cells. Complex Ir1 induces reactive oxygen species (ROS) production, mitochondrial dysfunction, and endoplasmic reticulum (ER) stress in MDA-MB-231 cells upon photoirradiation, leading to apoptotic cell death. The favorable PDT performance of Ir1in vivo has been further demonstrated in tumour-bearing mice. Together, the results suggest that Ir1 is a promising photosensitizer for mitochondria-targeted imaging and cancer phototherapy.

Digit ratio (2D:4D) in Chinese women with breast cancer.

OBJECTIVES: Digit ratio, especially second-to-fourth digit ratio (2D:4D) is established in utero and is positively correlated with oestrogen in men and women. It is a putative biomarker for prenatal hormone exposure and may represent an individual predisposition to certain diseases (e.g., breast cancer). The aim of the present study is to investigate whether there is a link between digit ratio (2D:4D) and breast cancer in Chinese populations. METHODS: The controls we chose were healthy subjects-age and -sex matched to the patients diagnosed with breast cancer. Photocopies of the two hands of 218 women (controls: 109; patients: 109) were collected. Left hand, right hand, mean hand, and right minus left 2D:4D (Dr-l ) were analyzed. RESULTS: The patients with breast cancer presented significantly higher 2D:4D than controls (left: P < 0.01; right: P < 0.05; mean: P < 0.05). The mean values of 2D:4D on the left hand were significantly higher than those on the right hand in the two groups, respectively (controls: P < 0.05; patients: P ≤ 0.01). In patients, there was a significantly negative correlation between 2D:4D (left hand: P < 0.01; right hand, mean: P < 0.05) and the presented age with breast cancer, but no association between Dr-l and age of presented disease. CONCLUSIONS: Digit ratio (2D:4D) may correlate with the increased risk of breast cancer.