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Background: The present study aimed to investigate the underlying role of interferon-regulatory factor 2 (IRF2)-inositol polyphosphate-4-phosphatase, type-II (INPP4B) axis in the regulation of autophagy in acute myeloid leukemia (AML) cells., Methods: Quantitative real time PCR (QRT-PCR) and western blot were performed to determine the expression levels of IRF2, INPP4B and autophagy-related markers in AML cell lines. Autophagy was assessed by elevated Beclin-1 expression, the conversion of light chain 3 (LC3)-I to LC3-II, downregulated p62 expression and green fluorescent protein (GFP)-LC3 puncta formation. The colony formation and apoptosis assays were performed to determine the effects of IRF2 and INPP4B on the growth of AML cells., Results: IRF2 and INPP4B were highly expressed in AML cell lines, and were positively correlated with autophagy-related proteins. Overexpression of IRF2 or INPP4B stimulated autophagy of AML cells, whereas inhibition of IRF2 or INPP4B resulted in the attenuation of autophagy. More importantly, IRF2 or INPP4B overexpression reversed autophagy inhibitor, 3-methyladenine (3-MA)-induced proliferation-inhibitory and pro-apoptotic effects, while IRF2 or INPP4B silencing overturned the proliferation-promoting and anti-apoptotic effects of autophagy activator rapamycin., Conclusion: IRF2-INPP4B signaling axis attenuated apoptosis through induction of autophagy in AML cells.

Objective: To screen the anti-tumor fraction of ethanol extracts from Thymus quinquecostatus Celak and investigate its anti-tumor effect on human leukemia cell line., Methods: Ethyl acetate, n-butanol and acetone fractions were separated from the ethanol extracts of wild Thymus quinquecostatus Celak. Growth inhibiting effects of these extracts on human leukemia cell lines K562 and HL-60 were determined by live cell counting and cell growth curve analysis. The possible anti-tumor mechanism was studied by morphological analysis with norcantharidin as a positive control., Results: Ethyl acetate fraction could significantly inhibit the proliferations of K562 and HL-60 cells, and the inhibiting effect depended on the concentration of ethyl acetate fraction. Ethyl acetate fraction could induce apoptosis of K562 and HL-60 cells. The n-butanol and acetone fractions had no significant inhibiting effect on K562 and HL-60 cells., Conclusion: Ethyl acetate fraction is the major anti-tumor fraction in ethanol extracts from Thymus quinquecostatus Celak.

Five triorganotin (IV) complexes, [(Ph3Sn)2L] (1) [(Me3Sn)2L]n (2), [(n‐Bu3Sn)2L]n (3), [(n‐Bu 3Sn)2L(4,4′‐bpy)]n (4), [(n‐Bu3Sn)2L(bpe)]n (5) [H2L = 4,4′‐stilbenedicarboxylic acid, 4,4′‐bpy = 4,4′‐bipyridine, bpe = 4,4′‐vinylenedipyridine], were successfully prepared and structurally characterized by FT‐IR, elemental analysis, NMR spectroscopy, PXRD, and X‐ray crystallography. Complex 1 is a monomer containing two tin atoms, and 1D infinite chains can be formed between the monomers through CH···π interactions. Complexes 2 and 3 represent 2D network structures containing tetranuclear 38‐membered rings. Meanwhile, complexes 4 and 5 are 1D chain‐like structures and form the 2D network and 3D stereo structure via CH···O intermolecular interactions, respectively. The anticancer activities of the complexes were investigated against different cancer cells (A549, HeLa, and HepG‐2). Complexes 1 and 3–5 showed superior anticancer activity. Meanwhile, the anticancer mechanism of complex 1 was studied with the results that complex 1 can promote the production of excessive reactive oxygen species, induce mitochondrial membrane permeability depolarization, and release proapoptotic factors from mitochondria into the cytosol, followed by caspase‐3 activation, nuclei damage, and apoptosis. Excitingly, complex 1 also has good antimetastatic ability toward HepG‐2 cancer cells. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is the third major cause of cancer-related death worldwide and responds positively to tyrosine kinase inhibitors (TKIs). Dasatinib (Das) is an Src/Abl family kinase and has been successfully utilized in the treatment of various cancers. Cancer cells are known to limit their oxidative phosphorylation to minimize oxidative stress. Palmitoylcarnitine (Pcar) incubation triggers mitochondria-mediated apoptosis in cancer cells by increasing the mitochondrial respiration rate. It stimulates the H2O2 production in cancer cells and thus induces oxidative stress. Thus, considering the above observations, the combined effect of Pcar and Das on HepG2, liver cancer cells has been evaluated in the present study. Results demonstrated that combined exposure to Pcar and dasatinib inhibited cell growth, proliferation, and invasion efficiency of cancerous cells more than single-drug treatment. Further, cells undergo membrane depolarization and caspase-dependent apoptosis upon exposure to combined treatment. In addition, in vivo study showed that Pcar and dasatinib treatment reduced the tumor size in mice more significantly than single-drug treatment. Thus, considering the above remarks, combined therapy of Pcar and dasatinib may serve as a potential candidate in the treatment of liver cancer in human and animal tissues. [ABSTRACT FROM AUTHOR]

Puffballs are a class of fungi widely distributed worldwide and associated with various bioactivities. This research mainly showed the antitumor bioactivity of extracts from Calvatia lilacina (CL), which is a common variety of puffballs. NMR and high-performance liquid chromatography methods are used to characterize the extracts. Results showed that CL extracts obtained with petroleum ether, ethyl acetate, ethanol, and water elicited obvious inhibitory effects on the proliferation of A549, Caco-2, and MDA-MB-231. Among these extracts, petroleum ether extract demonstrated the highest performance. This extract was then separated into seven sub-fractions (SFs). Three of these SFs (3#, 6#, and 7#) induces a decrease in the viability of MDA-MB-231 cells in which 7# SF exhibited the highest cytotoxicity, where the major component was found to be ergosta-7,22-dien-3-one. Further tests revealed that 7# SF from petroleum ether extract could trigger severe cell death in human breast cancer cells (MDA-MB-231) by activating the apoptotic pathway dependent on mitochondrial reactive oxygen species and caspase activation. All these results in combination indicate that the mechanism of extract-potentiated apoptosis associates closely with ROS-dependent mitochondrial dysfunction events which further induces mitochondria-mediated intrinsic cytochrome C-caspase-related pathway of apoptosis. Supplemental data for this article is available online at https://doi.org/10.1080/01635581.2021.1936576 [ABSTRACT FROM AUTHOR]

Abstract: Considerable recent evidence suggests that in addition to its neuromodulatory role, galanin, like several other neuropeptides, also plays an important trophic role during development and after adult neural injury. Studies in our laboratory have identified high levels of galanin and galanin receptor expression in the subventricular zone, rostral migratory stream, subgranular zone of dentate gyrus and the medial corpus callosum – which include the main sites for continuing cell proliferation in both adult and developing rat brain. Galanin expression was also strongly and transiently induced in oligodendrocyte progenitor cells (OPCs) throughout the neocortex and corpus callosum by a benign physiological stimulus, cortical spreading depression (CSD). SD-like depolarization also occurs in peri-infarction areas following cerebral ischemia and is associated with proliferation of OPCs and transiently increased galanin expression. Together, these data suggest a putative role for galanin in regulating progenitor or ‘stem cell’ proliferation, migration and/or differentiation. Cultured adult and embryonic stem cells or ‘neurospheres’ express galanin and galanin receptor mRNA and preliminary studies suggest that sub-acute galanin treatment of cultured neurospheres decreases cell proliferation/survival, possibly by effects on the rate of apoptosis via GalR2 receptors. [Copyright &y& Elsevier]

Six novel organotin phosphonate complexes, [(Me 3 Sn) 4 (HL1) 4 ] n 1 , [(Me 3 Sn) 2 (HL2) 2 ] n 2 , [(Me 3 Sn) 2 L3(H 2 O)] n 3 , [(Ph 3 Sn)(HL1)] 6 4 , [(Ph 3 Sn) 2 L2] n 5 and [(Ph 3 Sn) 2 L3] 6 6 , derived from phosphonic acid ligands [NaHL1 = 1-C 10 H 7 OPO 2 (OH)Na, H 2 L2 = 1-C 10 H 7 PO(OH) 2 , H 2 L3 = 2-C 10 H 7 PO(OH) 2 ], have been synthesized and characterized by elemental analysis, FT-IR, NMR (1H, 13C, 31P and 119Sn) spectroscopy and X-ray crystallography. The structural analysis reveals that complexes 1 and 5 display 1D infinite zig-zag chain structures, and complex 2 shows 1D right-handed helical chain structure, while complex 3 displays 1D left-handed helical chain structure. Complexes 4 and 6 are 24-membered macrocyclic rings interconnected by P, O and Sn atoms. Additionally, the molecules of complexes 1 and 3 are further linked through intermolecular π···π and O-H···O interaction into supramolecular structures, respectively. Furthermore, we preliminarily estimated in vitro cytostatic activity of complexes 1 – 6 against the human cervix tumor cells (HeLa), human hepatocellular carcinoma cells (HepG-2) and human normal breast cells (HBL-100). Importantly, the anti-proliferative properties and possible pathway of complex 6 are investigated, and the results demonstrate that complex 6 could induce apoptotic cell death via an overload of intracellular reactive oxygen species (ROS) levels and the dysfunctional depolarization of mitochondrial membranes. Triphenyltin phosphonates showed higher anti-proliferative activity against human cervix tumor cells, human hepatocellular carcinoma cells (HepG-2) and human breast cells. Mechanism of organotin phosphonates against HepG-2 was investigated, which indicated complexes could induce apoptosis by promoting excessive reactive oxygen species generation and causing the collapse of the mitochondrial membrane potential. Unlabelled Image • 4 and 6 with formulas [(Ph 3 Sn)(1-C 10 H 7 OPO 3 H)] 6 , [(Ph 3 Sn) 2 (2-C 10 H 7 OPO 3)] 6 are prepared. • Complexes 4 and 6 are 24-membered macrocyclic rings and cavity sizes are similar. • The organotin(IV) phosphonates with triphenyl show higher anticancer activities. • Complex 6 could induce cellular reactive oxygen species accumulation. • Complex 6 could lead to decreased of mitochondrial membrane potential. [ABSTRACT FROM AUTHOR]