Activation of GRP78 ATPase suppresses A549 lung cancer cell migration by promoting ITGB4 degradation

Hypochlorous acid (HOCl) is an essential signal molecule in cancer cells. Activated GRP78 ATPase by a HOCl probe named ZBM-H inhibits lung cancer cell growth. However, the role and underlying mechanism of GRP78 ATPase in lung cancer cell migration have not been established. Here, we reported that activation of GRP78 ATPase by ZBM-H suppressed A549 cell migration and inhibited EMT process. Notably, ZBM-H time-dependently decreased the protein level of integrin β4 (ITGB4) in A549 cells. Combinatorial treatment of 3BDO (an autophagy inhibitor) and ZBM-H partially rescued the protein level of ITGB4. Consistently, 3BDO partially reversed ZBM-H-inhibited cell migration. Furthermore, ZBM-H promoted the interaction between ANXA7 and Hsc70, which participated in the regulation of selective autophagy and degradation of ITGB4.</p

Marsupellins A–F, <i>ent</i>-Longipinane-Type Sesquiterpenoids from the Chinese Liverwort <i>Marsupella alpine</i> with Acetylcholinesterase Inhibitory Activity

Acetylcholinesterase (AChE) inhibitory activity-guided fractionation of the Chinese liverwort <i>Marsupella alpine</i> afforded six new [marsupellins A–F (<b>1</b>–<b>6</b>)] and three known (<b>7</b>–<b>9</b>) <i>ent</i>-longipinane-type sesquiterpenoids. The structures were determined from MS and NMR spectroscopic data, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds <b>1</b>–<b>9</b> exhibited moderate to weak AChE inhibitory activity

<i>ent</i>-Kaurane Diterpenoids from Chinese Liverworts and Their Antitumor Activities through Michael Addition As Detected in Situ by a Fluorescence Probe

It is generally accepted that the origin of the cytotoxicity of <i>ent</i>-kaurane diterpenoids is due to the formation of reactive oxygen species (ROS) and that the α,β-unsaturated carbonyl is a pivotal moiety. Herein we demonstrate the isolation of 32 new and 12 known <i>ent</i>-kaurane diterpenoids from two Chinese liverworts. These compounds and three semisynthesized derivatives were screened against human cancer cell lines. The results revealed that their anticancer activities are caused by ROS formation through Michael modification of the protein thiols and depletion of glutathione unselectively. We also found that <i>N</i>-acetylcysteine reverses the cytotoxicity of these diterpenoids by forming Michael adducts, not through a well-recognized ROS scavenging pathway as previously reported. In situ intracellular thiol detection helped us visualize the intracellular distribution of the diterpenoids and determine the potency of their cytotoxicity. An alkaline analogue was found to be more selective because of the altered subcellular distribution