Hypericin-mediated photodynamic therapy induces apoptosis in K562 human leukemia cells through JNK pathway modulation

Abstract

Hypericin (Hyp) is traditionally used as an antidepressant and antiviral agent. It selectively accumulates in spheroids and is also used as a photosensitizer in the photodynamic therapy of cancer. The present study aimed to investigate the cytotoxic effect of Hyp-mediated photodynamic therapy (Hyp-PDT) on cell growth and apoptosis of K562 leukemia cells, and to examine the underlying mechanisms. Hyp-PDT was performed with different light intensities (0.1, 0.3 and 0.5 mW/cm2), different concentrations of Hyp (0, 0.2, 0.4 and 0.8 µg/ml) and different durations of irradiation (0, 2, 4 and 8 min) in order to select the optimal conditions for subsequent experiments. A concentration of 0.4 µg/ml Hyp with a 5 h drug-light interval and 4 min irradiation at 0.3 mW/cm2 light intensity was selected as the optimal conditions. The effects of Hyp-PDT on apoptosis were determined by detecting morphological changes under microscopy and by performing western blot analysis. The results revealed that Hyp-PDT suppressed cell viability in a light intensity-, dose- and irradiation duration-dependent manner. The expression levels of cleaved caspase-9, cleaved caspase-3 and phosphorylated-C-Jun N terminal kinase (JNK) l were significantly upregulated following Hyp-PDT. These results indicated that Hyp-PDT decreased cell viability and induced mitochondria-caspase-dependent apoptosis in the K562 cells through regulation of the JNK pathway. These findings suggest that Hyp-PDT may be developed as an effective treatment for leukemia.

Exploring Modes of Photokilling by Hypericin

“…Paraptosis was initially described as a response to ER stress, with JNK and MAPK/ERK pathways involved (15,16). These pathways are also stimulated by the photodynamic action of hypericin (6,7,26‐28). Whether MAPK effects are a cause of or a response to PDT‐related photodamage is not entirely clear.…”

Histone deacetylase 2 is involved in �‑opioid receptor suppression in the spinal dorsal horn in a rat model of chronic pancreatitis pain

“…It has been reported that the overexpression of pro-inflammatory cytokines during CP induction, such as TNF-, IL-1β and IL-6 may promote the allodynia of CP rats ( 18 , 26 ), and these mediators may induce the activation of JNK and extracellular signal-regulated kinase (ERK) signaling pathways, which serve important roles in the maintenance of chronic pain. IL-1β is the most important inflammatory mediator that causes pancreatic islet dysfunction and destruction, which may promote activation of JNK ( 27 – 29 ); previous studies have also demonstrated positive effect of TNF-α and IL-6 on JNK activation ( 30 – 32 ). MOR expression is mainly regulated by signaling pathways such as JNK ( 17 ).…”

Facile fabrication of hypericin-entrapped glyconanoparticles for targeted photodynamic therapy

“…It has been widely used as antidepressant, antiviral, and antiretroviral agents in the past decades. [15][16][17] Recently, Hy has attracted much attention as a potent PS with substantial quantum yield, low photobleaching, a large excitation range, and negligible dark cytotoxicity. 7,17,18 However, like most PSs, Hy is highly hydrophobic and cannot dissolve in aqueous medium, which reduces its photodynamic property and shortens its circulation time in blood in vivo, thus affecting its accumulation in the tumor site and weakening the effect of PDT for cancer therapy.…”