Background: The aim of this study was to characterize the disorder of lipid metabolism in hepatocellular carcinoma (HCC). HCC is a worldwide disease. The research into the disorder of lipid metabolism in HCC is very limited. Study of lipid metabolism in liver cancer tissue may have the potential to provide new insight into HCC mechanisms. Methods: A lipidomics study of HCC based on Ultra high performance liquid chromatography-electronic spray ionization-QTOF mass spectrometer (UPLC-ESI-QTOF MS) and Matrix assisted laser desorption ionization-fourier transform ion cyclotron resonance mass spectrometer (MALDI-FTICR MS) was performed. Results: Triacylglycerols (TAGs) with the number of double bond (DB) > 2 (except 56:5 and 56:4 TAG) were significantly down-regulated; conversely, others (except 52:2 TAG) were greatly up-regulated in HCC tissues. Moreover, the more serious the disease was, the higher the saturated TAG concentration and the lower the polyunsaturated TAG concentration were in HCC tissues. The phosphatidylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol (PI) were altered in a certain way. Sphingomyelin (SM) was up-regulated and ceramide (Cer) were down-regulated in HCC tissues. Conclusions: To our knowledge, this is the first such report showing a unique trend of TAG, PC, PE and PI. The use of polyunsaturated fatty acids, like eicosapentanoic and docosahexanoic acid, as supplementation, proposed for the treatment of Non-alcoholic steatohepatitis (NASH), may also be effective for the treatment of HCC.

MALDI MSI has been recently applied as an innovative tool for detection of molecular distribution within a specific tissue. MALDI MSI requires deposition of an organic compound, known as matrix, on the tissue of interest to assist analyte desorption and ionization, in which the matrix crystal homogeneity and size greatly influence the imaging reproducibility and spatial resolution in MALDI MSI. In this work, a homemade electrospray deposition device was developed for deposition of matrix in MALDI MSI. The device could be used to achieve 1 μm homogeneous matrix crystals in MALDI MSI analysis. Moreover, it was found, for the first time, that the electrospray deposition device could be used to precisely control the matrix crystal size, and the imaging spatial resolution was increased greatly as the matrix crystals size becoming smaller. In addition, the easily-built electrospray deposition device was durable for acid, base or organic solvent, and even could be used for deposition of nanoparticles matrix, which made it unparalleled for MALDI MSI analysis. The feasibility of the electrospray deposition device was investigated by combination with MALDI FTICR MSI to analyze the distributions of lipids in mouse brain and liver cancer tissue section.

Background— Apoptosis repressor with caspase recruitment domain (ARC) is abundantly expressed in cardiomyocytes. Protein kinase CK2 can phosphorylate ARC at threonine-149, thereby enabling ARC to antagonize apoptosis. ARC phosphorylation occurs in a constitutive manner. Nevertheless, cardiomyocytes still undergo apoptosis that is related to cardiac diseases such as myocardial infarction and heart failure. Whether the occurrence of apoptosis is related to the loss of protection by ARC under pathological conditions remains unknown. Methods and Results— ARC phosphorylation levels are decreased in cardiomyocytes treated with isoproterenol or aldosterone. We explored the molecular mechanism by which ARC phosphorylation levels are decreased. Our results reveal that either direct incubation or coexpression with calcineurin leads to a decrease in ARC phosphorylation levels. Inhibition of calcineurin can attenuate the reduction in ARC phosphorylation levels on treatment with isoproterenol or aldosterone. These data indicate that the reduction in ARC phosphorylation levels is related to its dephosphorylation by calcineurin. Our results further reveal that ARC can prevent isoproterenol- and aldosterone-induced apoptosis, but this function depends on its phosphorylation status. Isoproterenol and aldosterone upregulate Fas ligand expression, and Fas ligand and caspase-8 are required for isoproterenol and aldosterone to induce apoptosis. However, phosphorylated but not dephosphorylated ARC is able to inhibit caspase-8–mediated apoptosis. Phosphorylated ARC exerts its effects against caspase-8 by directly associating with procaspase-8 and inhibiting its interaction with Fas-associated protein with death domain. Conclusions— Our study identifies a novel cardiac apoptotic pathway in which ARC is dephosphorylated by calcineurin. This pathway could be a component in the cardiac apoptotic machinery.

Numerous studies have demonstrated the apoptotic and anti‑proliferative effects of resveratrol, a natural polyphenolic phytoalexin, on various cancer cell lines. However, the effects of resveratrol on the regulation of human cervical carcinoma, and the mechanisms underlying these effects, remain to be elucidated. In the present study, the potential mechanisms underlying the effects of resveratrol in HeLa cervical carcinoma cells were investigated. The results revealed that resveratrol inhibited proliferation and induced apoptosis in HeLa human cervical cancer cells in a dose‑dependent and time‑dependent manner. Resveratrol induced cell shrinkage in HeLa cells and apoptosis accompanied by the activation of caspase‑3 and ‑9. Furthermore, resveratrol upregulated the expression of the pro‑apoptotic B‑cell lymphoma (Bcl)‑2‑associated X protein and downregulated the expression of the anti‑apoptotic proteins Bcl‑2 and Bcl‑extra large in HeLa cells. In addition, p53, a protein that is essential for cell survival and cell cycle progression, exhibited elevated expression levels in resveratrol‑treated HeLa cells. Therefore, resveratrol may be a promising novel inhibitor of human cervical cancer.

Cyclometallated platinum(II) complexes, [(C^N^N)Pt^II(L)]ⁿ⁺ (n = 0 or 1), have attracted much attention due to their potency as luminescent probes for nucleic acids and anticancer agents. Reported herein are four [(C^N^N)Pt^II(L)]⁺ complexes (5–8, L = 4-anilinoquinazoline derivative) which exhibit a weak fluorescence emission over 605 to 627 nm upon excitation at 405 nm. The ligation of the cyclometallated platinum cores with EGFR-inhibiting anilinoquinazolines not only confers the resulting complexes with excellent EGFR-inhibiting potency with IC₅₀ values at the nanomolar level, but also enhances their affinity to DNA, in particular to G-quadruplex (G4) DNA. Such interactions produce strongly luminescent EGFR and DNA complexes, respectively, allowing the easy tracing of the cellular uptake and distribution of the platinum complexes and make them potential fluorescent probes for both EGFR and DNA in living cells. Complexes 5 and 6 are highly cytotoxic to the cancer cell lines A549, HeLa, A431 and MCF-7, and selectively inhibit the EGF-stimulated growth of the MCF-7 cell line. Secondary-ion mass spectrometry imaging and ICP-MS analysis demonstrated that the platinum complexes localize both on the cell membrane and in the nuclei of cells associated with EGFR and DNA binding, respectively, further verifying their dual-targeting feature as anticancer agents.

An organometallic ruthenium complex exhibits excellent inhibitory activity against EGFR and high affinity towards DNA via minor groove binding, effectively inducing early stage apoptosis of A549 lung cancer cells.