Perturbations in cellular chloride concentrations can affect cellular pH and autophagy and lead to the onset of apoptosis. With this in mind, synthetic ion transporters have been used to disturb cellular ion homeostasis and thereby induce cell death; however, it is not clear whether synthetic ion transporters can also be used to disrupt autophagy. Here, we show that squaramide-based ion transporters enhance the transport of chloride anions in liposomal models and promote sodium chloride influx into the cytosol. Liposomal and cellular transport activity of the squaramides is shown to correlate with cell death activity, which is attributed to caspase-dependent apoptosis. One ion transporter was also shown to cause additional changes in lysosomal pH, which leads to impairment of lysosomal enzyme activity and disruption of autophagic processes. This disruption is independent of the initiation of apoptosis by the ion transporter. This study provides the first experimental evidence that synthetic ion transporters can disrupt both autophagy and induce apoptosis.
Findings of this study confirmed the therapeutic value of plants in the hospital environment as a noninvasive, inexpensive, and effective complementary medicine for surgical patients. Health care professionals and hospital administrators need to consider the use of plants and flowers to enhance healing environments for patients.
Using various medical and psychological measurements, this study performed a randomized clinical trial with surgical patients to evaluate if plants in hospital rooms have therapeutic influences. Ninety patients recovering from an appendectomy were randomly assigned to hospital rooms with or without plants. Patients in the plant treatment room viewed eight species of foliage and flowering plants during their postoperative recovery periods. Data collected for each patient included length of hospitalization, analgesics used for postoperative pain control, vital signs, ratings of pain intensity, pain distress, anxiety, and fatigue, the State-Trait Anxiety Inventory Form Y-1, the Environmental Assessment Scale, and the Patient's Room Satisfaction Questionnaire. Patients in hospital rooms with plants and flowers had significantly fewer intakes of postoperative analgesics, more positive physiological responses evidenced by lower systolic blood pressure and heart rate, lower ratings of pain, anxiety, and fatigue, and more positive feelings and higher satisfaction about their rooms when compared with patients in the control group. Findings of this research suggested that plants in a hospital environment could be noninvasive, inexpensive, and an effective complementary medicine for patients recovering from abdominal surgery.
The heat shock protein HSP70 plays antiapoptotic and oncogenic roles, and thus its inhibition has been recognized as a potential avenue for anticancer therapy. Here we describe the small molecule, apoptozole (Az), which inhibits the ATPase activity of HSP70 by binding to its ATPase domain and, as a result, induces an array of apoptotic phenotypes in cancer cells. Affinity chromatography provides evidence that Az binds HSP70 but not other types of heat shock proteins including HSP40, HSP60, and HSP90. We also demonstrate that Az induces cancer cell death via caspase-dependent apoptosis by disrupting the interaction of HSP70 with APAF-1. Animal studies indicate that Az treatment retards tumor growth in a xenograft mouse model without affecting mouse viability. These studies suggest that Az will aid the development of new cancer therapies and serve as a chemical probe to gain a better understanding of the diverse functions of HSP70.
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