Page 149 - D. Cancer biology

Effect of hispidulin on TRAIL-induced apoptosis in cancer cells through
CaMKKβ/AMPK/USP51 axis-mediated Bim stabilization
Seon Min Woo, Kyoung-jin Min and Taeg Kyu Kwon*

Department of Immunology, School of Medicine, Keimyung University, Daegu, Korea.
BACKGROUND AIM

Hispidulin (4’,5,7-trihydroxy-6-methoxyflavone) is To overcome TRAIL resistance, we need more efficient therapeutic strategy,
natural compound, and has multiple functions, such as combination treatment. Combination treatment might reduce adverse
effects, and increase anti-cancer effects. Most of sensitizers of cancer cells to
including anti-inflammation, anti-fungal, anti-epileptic, anti-cancer drugs modulate apoptosis-related proteins or signaling pathways,
anti-hypnotic, and anti-osteoclastogenesis. In addition, which are involved in cell survival and proliferation. Here, we investigate
whether hispidulin sensitizes cancer cells to TRAIL, and we identify the
hispidulin has the potential anti-cancer effects. molecular mechanisms which involved in hispidulin plus TRAIL-induced
apoptosis.
RESULTS
Figure 1 Figure 2 Figure 3

Figure 4 Figure 5 Figure 6

Hispidulin has the potential anti-cancer effects. For examples, hispidulin induces apoptosis in leukemia and hepatoblastoma cells [6,7], and suppresses angiogenesis, leading to inhibition of tumor
growth in xenograft mice models. However, the study of mechanisms and the synergistic effects by the combination treatment with sub-lethal concentrations of anti-cancer drugs and hispidulin are still
an unclear. Here, we demonstrated that combined treatment with hispidulin and TRAIL has synergistic anti-cancer effects in cancer cells and in in vivo xenograft models. We found that stabilization of
Bim by hispidulin is a critical factor for combined treatment-induced apoptosis, and AMPK activation is related with Bim stabilization. AMPK increased Bim protein stability via up-regulation of USP51
expression in hispidulin-treated cells. Therefore, we suggested that hispidulin could enhance TRAIL-mediated apoptosis via CaMKKβ/AMPK/USP51axis-mediated Bim stabilization.
CONCLUSION REFERENCES ACKNOWLEDGEMENTS

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