Bufalin sensitizes human bladder carcinoma cells to TRAIL-mediated apoptosis

Abstract

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily, has garnered interest as it is relatively non-toxic to normal cells, but selectively induces apoptotic cell death in multiple types of transformed or malignant cells. Bufalin is the major digoxin-like immunoreactive component of Sum Su, which is obtained from the skin and parotid venom gland of the toad. Bufalin is known to inhibit cell proliferation and induce apoptosis in a variety of cancer cells. The present study investigated whether bufalin promoted TRAIL-induced apoptotic cell death. In the present study, a combined treatment using bufalin and TRAIL significantly increased TRAIL-mediated inhibition of cell viability and increased apoptosis in T24 human bladder cancer cells. The apoptotic effects were associated with the upregulation of death receptor proteins and the downregulation of cellular Fas-associated death domain-like interleukin-1β-converting enzyme inhibitory protein and X-linked inhibitor of apoptosis protein. Furthermore, the data revealed that bufalin and TRAIL activated caspase-3, −8 and −9 and subsequently increased the degradation of poly (ADP-ribose) polymerase. Taken altogether, the nontoxic doses of bufalin and TRAIL sensitized T24 cells to TRAIL-mediated apoptosis. Therefore, bufalin may provide an effective therapeutic strategy for the safe treatment of human bladder cancers that are resistant to TRAIL.

Anti-tumor Activity of Bufalin by Inhibiting c-MET Mediated MEK/ERK and PI3K/AKT Signaling Pathways in Gallbladder Cancer

“…Among these effects, the anti-tumor activity of Bufalin has caught the attention of many researchers. A large number of studies have indicated that Bufalin has the inhibitory effect on many kinds of malignant tumors, such as liver cancer [25], colorectal cancer [26], bladder cancer [27], gallbladder cancer [28], pancreatic cancer [29] and gastric cancer [30].…”

Bufalin inhibits gastric cancer invasion and metastasis by down-regulating Wnt/ASCL2 expression

“…Bufalin is a bioactive polyhydroxysteroid isolated from Venenum Bufonis, also called Chan Su, a well-known traditional Chinese medicine widely used in cancer treatment in China [ 4 , 23 ]. Recent studies have shown that bufalin has anti-cancer activity in various cancers, such as breast cancer [ 24 ], osteosarcoma [ 5 ], colon cancer [ 11 , 25 ], lung cancer [ 26 ], pancreatic cancer [ 27 ], bladder cancer [ 28 ] and hepatocellular carcinoma [ 9 ]. Studies had found that bufalin inhibits GC proliferation, induces apoptosis and reverses cisplatin resistance [ 12 , 13 ].…”

Andrographolide Enhances TRAIL-Induced Apoptosis via p53-Mediated Death Receptors Up-Regulation and Suppression of the NF-кB Pathway in Bladder Cancer Cells

“…However, evidence indicates that cancer cells can develop resistance to TRAIL if they lose the ability to express death receptors or exhibit constant activation of anti-apoptotic pathways 9, 10. Certain malignant cells are resistant to TRAIL, including bladder cancer cells 11-13. Therefore, identifying effective agents capable of overcoming TRAIL resistance in bladder cancer cells is necessary.…”