Cancer is a major global public health problem with high morbidity. Depression is known to be a high-frequency complication of cancer diseases that decreases patients' life quality and increases the mortality rate. Therefore, antidepressants are often used as a complementary treatment during cancer therapy. During recent decades, various studies have shown that the combination of antidepressants and anticancer drugs increases treatment efficiency. In recent years, further emerging evidence has suggested that the modulation of autophagy serves as one of the primary anticancer mechanisms for antidepressants to suppress tumor growth. In this review, we introduce the anticancer potential of antidepressants, including tricyclic antidepressants (TCAs), tetracyclic antidepressants (TeCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs). In particular, we focus on their autophagy-modulating mechanisms for regulating autophagosome formation and lysosomal degradation. We also discuss the prospect of repurposing antidepressants as anticancer agents. It is promising to repurpose antidepressants for cancer therapy in the future.
Reactive oxygen species (ROS) are significant active species in living organisms, and their coordination maintains the function of organelles to resist the invasion of foreign substances. Hypochlorous acid (HClO) is not only an eventful signaling species but also a kind of ROS, which plays an irreplaceable role in the immune system. However, its abnormal levels can cause cell damage or even apoptosis, which in turn leads to the onset of a series of diseases such as inflammation, neurological diseases, and even cancer. Based on this, we designed a near-infrared fluorescent probe with a large Stokes shift for ultrafast response to HClO. Furthermore, the probe exhibits excellent sensitivity and selectivity toward HClO over other species. The probe was successfully applied to visualize endogenous and exogenous HClO in living cells and in zebrafish. This unique study is the key to providing a trustworthy tool for imaging based on the in vitro and in vivo imaging of endogenous HClO, which possesses great potential for the use in future studies of HClO-related biology and pathology.
Peroxynitrite (ONOO−), a highly reactive nitrogen species, which plays a crucial role in numerous physiological and pathological processes of cell functionalization. The anomalous concentration of ONOO− may result in a range of diseases, such as arthritis, neurological disorders, and even cancer. Therefore, it is urgent to develop a simple and effective tool to monitor the fluctuation of ONOO− levels in biological systems. Herein, an ultrafast fluorescent probe (HND-ONOO) is proposed to detect ONOO−, which displays brilliant fluorescence in less than 30 s with a large Stokes shift. Furthermore, the probe exhibited the lower detection limit (48 nM) and satisfactory results in differentiating ONOO− from other related species. The probe that possesses good biocompatibility and low toxicity was employed to monitor the level of exogenous and endogenous ONOO− in living cells. Thus, the probe HND-ONOO could be served as a potential imaging tool to visualize intracellular ONOO− and understand the relationship between ONOO− and inflammation.
A coumarin-based dual responsive fluorescent probe with a simple structure was developed for the detection of Cys and HSO3 -. Under simulated physiological conditions, Cou-F displayed an on-off fluorescence response to Cys at 521 nm and an off-on fluorescence response to HSO3 - at 500 nm. Furthermore, Cou-F had the advantages of high sensitivity, strong specificity and rapid response. The detection limits of Cou-F toward Cys and HSO3 - were 0.54 μM and 0.65 μM, respectively. Cou-F enabled high selective responses to Cys and HSO3 - over other biologically related species. The response times of Cou-F toward Cys and HSO3 - were 80 s and 100 s. The fluorescence imaging of Cys and HSO3 - was achieved in living RAW246.7 cells.
Hypochlorous acid (HOCl), a highly potent oxidant of reactive oxygen species, plays critical roles in many physiological and pathological processes. In this work, a novel coumarin-based fluorescent probe, Cou-HOCl, was prepared for the detection of HOCl. The probe exhibited good selectivity over other analytes, excellent sensitivity with a detection limit of 16 nM, and fast response within 5 s. And further study demonstrated that the probe could be used not only to image exogenous HOCl in various cells, but also to determine the fluctuating levels of HOCl in macrophage cells during inflammation.
Sulfur dioxide (SO2), a possible endogenous gaseous signaling molecule, has been found to be correlated with various diseases in living organisms. Thus, the development of effective methods for detection of SO2 are of great physiological and pathological significance. In this work, we report a ratiometric NIR fluorescent probe Cou-Rh for monitoring bisulfite on basis of Michael addition reaction. This probe is prepared from coumarin by acid-catalyzed cyclization reaction. The addition of bisulfite results in a significant decrease of fluorescence intensity at 695 nm and enhancement at 550 nm. The probe also displays high selectivity over various biologically related analytes with nanomolar limit of detection. What’s more, fluorescence imaging further confirms that the probe is capable of detecting bisulfite in living cells and zebrafish larvae. The results demonstrate that probe Cou-Rh can be employed for a useful scaffold to study the physiological function of sulfur dioxide.