Page 36 - D. Cancer biology

[D. Cancer biology-26]

Inhibition of phospholipase D2 sensitizes breast cancer cells

to histone deacetylase inhibitor

MinJu Kang¹, Won Chan Hwang¹, Venu Venkatarame Gowda Saralamma¹, JuWon Kim¹, RaeHee Kang¹,
Hyun Ji Lee¹, Do Sik Min¹

¹College of Pharmacy, Yonsei University, InCheon 21983, Republic of Korea

Histone deacetylase (HDAC) inhibitors are promising anticancer drugs but their effect on tumor treatment has been

disappointing mainly due to the acquisition of HDAC inhibitor resistance. However, the mechanisms underlying such
resistance remain unclear. Herein, we demonstrate that suberoylanilide hydroxamic acid (SAHA), a HDAC inhibitor,

induces the expression of phospholipase D2 (PLD2) via activation of protein kinase C-ζ in breast cancer cells and
enhances the threshold for the cancer cells to undergo apoptosis. The combination treatment of SAHA with a PLD2

inhibitor significantly sensitized cell death and suppressed invasion, migration, and angiogenesis, compared with
that of either treatment. These results suggest that PLD2 is involved in the resistance of cancer cells to HDAC

inhibitors. These findings provide further insight into elucidating the advantages of combination therapy with HDAC
and PLD2 inhibitors over single-agent strategies for the treatment of cancer.