Guang-Xiong Zhou

Dysregulated metabolism is one of the major hallmarks of malignant tumors, which includes increased glycolysis even in the presence of ample oxygen, providing a metabolic advantage for cell proliferation and tumor growth. Recognition of metabolic reprogramming in oncogenesis has paved the way for developing novel therapeutic approaches and agents targeting the key enzymes involved in this process. The therapeutic potential of plant-derived natural bioactive compounds is promising, due to their diverse structures and multiple targets. Angoline, an isoquinoline alkaloid isolated, has been reported to inhibit cancer cell proliferation and tumor growth, but the underlying mechanisms remain largely unclear. Our results showed that Angoline effectively inhibits breast cancer cell proliferation and tumor growth. Mechanistically, angoline directly binds to LDHA and suppresses its activity, resulting in decreased glycolytic rates, less lactate production and increased oxygen consumption in breast cancer cells. Furthermore, the metabolic switch from aerobic glycolysis to oxidative phosphorylation by angoline treatment induces the accumulation of intracellular ROS, which in turn causes a decline in mitochondrial membrane potential and subsequently triggers autophagy. In vivo xenograft model further confirmed the efficacy and safety of angoline in breast cancer treatment. Together, these results suggested that Angoline is a promising natural compound to inhibit LDHA activity, leading to decreased glycolytic rate and increased autophagy related cell death in breast cancer cells. These data together reveal an underlying molecular mechanism of angoline to treat breast cancer.

Two new pregnane glycosides (1 and 2), together with four known ones (3– 6), were isolated from the roots of Cynanchum auriculatum Royle ex Wight (Asclepiadaceae). On the basis of detailed spectroscopic analysis and chemical method, the structures of new compounds were characterized to be metaplexigenin 3-O-β-D-cymaropyranosyl- (1→4)-α-L-diginopyranosyl-(1→4)-β-D-cymaropyranoside (1), metaplexigenin 3-O-α-L-diginopyranosyl-(1→4)-β-D-cymaropyranoside (2). All the isolated compounds (1–6) were tested for their in vitro inhibitory activity against the growth of human colon cancer cell lines HCT-116. Compounds 5 and 6 showed significant cytoxicities with IC₅₀ values of 43.58 µM and 52.21 µM.

Two new aryltetralin-type lignans (1-2) were isolated from the dichloromethane fraction of 95% ethanol extract of Camellia oleifera fruit husk. Their structures were elucidated on the basis of spectroscopic analysis, and the absolute configurations of compounds 1-2 were determined by the comparison of measured ECD curves with the quantum chemical calculated ones. The new compounds were tested for their antioxidant activities and cytotoxicity against three human cancer cell lines (Huh-7, H460 and MCF-7). While compounds 1 and 2 only showed slight DPPH radical scavenging activities with the IC₅₀ values of 38.68 ± 5.02 and 56.62 ± 1.49 μM, respectively. Graphical Abstract

A chemical investigation of 95% ethanol extract from the stem and branch of Tripterygium wilfordii has resulted in the isolation and characterization of two new compounds, one neolignan (1) and one phenylalanine derivative (2), as well as four known compounds (3–6). The structures of the new compounds were determined based on extensive spectroscopic analyses. The absolute configuration of compound 1 was defined by X-ray crystallographic analyses and electronic circular dichroism calculation. In addition, compounds 2 and 4–6 exhibited inhibitory effects against NO production in LPS-induced RAW 264.7 macrophages with the IC₅₀ value ranging from 3.51 μM to 30.40 μM.

Hemiactinomycin (1), an intermediate derivative of actinomycin biosynthesis, together with three known actinomycins (2-4) , were isolated from the ethanolic extract of Streptomyces antibioticus H41-55 fermentation mycelium by using various column chromatography. The structure of the derivative was established by extensive spectroscopic analysis, including HRESIMS, 1D, and 2D NMR spectroscopy. In addition, the anti-inflammatory activities of all the isolates were tested. The derivative (1) showed inhibiting NO release activities in LPS-induced RAW 264.7 macrophages with the IC₅₀ values of 15.41 ± 0.66 μM. Graphical Abstract