Pancreatic cancer cell apoptosis is induced by a proteoglycan extracted from Ganoderma lucidum.

The Traditional Chinese Medicine, Ganoderma lucidum, has been widely used for its immunity-related and anti-cancer effects. Fudan-Yueyang-Ganoderma lucidum (FYGL) is a proteoglycan, extracted from Ganoderma lucidum, that has shown safe anti-diabetic activity in vivo. The present study demonstrated that FYGL could selectively inhibit the viability of PANC-1 and BxPC-3 pancreatic cancer cells in a dose dependent manner, but not in Mia PaCa-2 pancreatic cancer cells and HepG2 liver cancer cells. In addition, FYGL could inhibit migration and colony formation, and promote apoptosis in PANC-1 cells, but not in Mia PaCa-2 cells. Further investigation into the underlying mechanism revealed that FYGL could inhibit the expression level of the Bcl-2 protein in PANC-1 cells, but not in Mia PaCa-2 cells, leading to an increase in reactive oxygen species (ROS) and a reduction in the mitochondrial membrane potential and cell apoptosis. The increased ROS also promoted the formation of autophagosomes, along with an increase in the microtubule-associated protein light chain 3 II/I ratio. However, FYGL halted autophagy by preventing the autophagosomes from entering the lysosomes. The inhibition of autophagy increased the accumulation of defective mitochondria, as well as the production of ROS. Taken together, the processes of ROS regulation and autophagy inhibition promoted apoptosis of PANC-1 cells through the caspase-3/cleaved caspase-3 cascade. These results indicated that FYGL could be potentially used as an anti-cancer agent in the treatment of pancreatic cancer.

NIR-controlled HSP90 inhibitor release from hollow mesoporous nanocarbon for synergistic tumor photothermal therapy guided by photoacoustic imaging.

Photothermal therapy (PTT) has been widely studied for tumor therapy. However, the clinical transformation of PTT has encountered significant challenges in tumor recurrence, because the uneven hyperthermia in tumor tissues can result in the survival of cancer cells in the lower temperature regions close to blood vessels (as the blood flow can dissipate the localized heat). It is therefore important for clinical treatments to retain the excellent therapeutic efficiency of PTT at relatively low temperatures. In this article, innocuous hollow mesoporous carbon spheres (HMCS) with a high photothermal conversion efficiency were obtained by a one-pot synthesis method. After modification with DSPE-PEG, the HMCS-PEG exhibited a superior stability in biomedia, which is beneficial for further biological applications. Interestingly, combined with hydrophobic gambogic acid (GA) which can downregulate heat shock protein 90 (HSP90), the HMCS-PEG-GA system showed a significant NIR-enhanced tumor therapeutic effect in vitro and in vivo under mild temperature conditions (∼43 °C), and the combination index (CI) value of HMCS-PEG-GA was found to be 0.72. Meanwhile, this nano-system possessed good photothermal imaging and photoacoustic imaging abilities. Guided by the photoacoustic imaging signal, HMCS-PEG-GA showed enormous potential for use in accurate tumor diagnosis and mild-temperature PPT treatment applications, which is very important for clinical transformation of this nano-system.