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

Abstract

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.

Identification of Molecular Targets and Underlying Mechanisms of Xiaoji Recipe against Pancreatic Cancer Based on Network Pharmacology

“…In pancreatic cancer, it has been reported that scoparone inhibits tumor progression via PI3K/Akt signaling pathway [ 9 ]. Besides, a proteoglycan extracted from Ganoderma lucidum can induce cancer cell apoptosis [ 10 ]. The prescription of Xiaoji recipe is mainly composed of Curcuma zedoaria (10 g, E Zhu), Polygonum cuspidatum (10 g, Huzhang), clematis root (10 g, Weilingxian), Rhizoma Paridis (10 g, Zhonglou), and Eupolyphaga Steleophaga (10 g, Tubiechong).…”

Autophagy: A Key Player in Pancreatic Cancer Progression and a Potential Drug Target

“…A proteoglycan extracted from Ganoderma lucidum known as Fudan-Yueyang-Ganoderma lucidum (FYGL) was found to increase autophagosome levels and prevent autolysosome fusion, indicating late-stage autophagic inhibition effects [ 363 ]. FYGL also reduced Bcl-2 expression and increased cleaved caspase-3 which led to increased ROS and reduced MMP, indicating apoptotic potential [ 363 ]. However, these results were only present in PANC-1 and not MiaPaCa2 cells, suggesting cell type specific effects and require further investigations.…”

Targeting autophagy in pancreatic cancer: The cancer stem cell perspective

“…Even though their exact mechanism of action is unclear, they seem to converge to a common path of apoptosis inhibition. Fudan-Yueyang-Ganoderma lucidum (FYGL; a proteoglycan extracted from Ganoderma lucidum) and Alantolactone demonstrated inhibitory effect in late-stage of autophagy along with increased apoptotic potential, mediated by elevated ROS production and suppression of STAT3 and Bcl-2 respectively (67)(68)(69)(70). Curcumin is also capable of inducing pro-apoptotic effects, by increasing the BAX/Bcl-2 ratio (71), while ursolic acid (UA) downregulated autophagy, predominantly via inducing cell cycle arrest (72).…”