3.2 TA inhibits the proliferation and growth of pancreatic
cancer cells
We subsequently examined whether the structural analogues of TA affected
the proliferation of pancreatic cancer cells (PANC-1, BxPC-3, and
Capan-2). Using the MTS assay, we confirmed that the structural
analogues of TA displayed differential inhibitory effects on the cell
proliferation of pancreatic cancer (Figure 2b). Among these compounds,
TA showed the strongest anti-proliferation activity against pancreatic
cancer cells. The preliminary structure-activity relationship of these
compounds showed that the position of the side chain attached onansa ring played an important role in the anticancer activity,
and the existence of a cyclohexyl group significantly improved the
activity. We further confirmed that TA also strikingly inhibited the
proliferation of several pancreatic cancer cell lines including CFPAC-1,
AsPC-1, MIA PaCa-2, HPAC and SW1990 (Figure 2c). Unexpectedly, TA
exhibited stronger proliferation suppressive activity against PANC-1
cells than other pancreatic cancer cell lines. Based on these results,
the PANC-1 cells were selected for subsequent experiments. The effect of
TA on the growth of PANC-1 cells was evaluated using the colony
formation assay. As shown in Figure 2d, TA significantly inhibited the
colony formation of PANC-1 cells compared with the control in a
concentration-dependent manner.
Additionally, the cell proliferation inhibitory activity of TA was
better than that of BP-1-102, a specific STAT3 inhibitor, in pancreatic
cancer (Figure S2a). In addition, we also examined whether TA restrained
the proliferation of other cancer cells and normal cell lines.
Interestingly, TA also strongly inhibited the proliferation of prostate
and breast cancer cells rather than
normal cell lines (Figure S2b). TA also significantly inhibited the
colony formation of other pancreatic cancer cells compared with their
control counterparts in a concentration-dependent way (Figure S3). These
results indicated that TA exerted a strong inhibitory effect on the
proliferation and growth of pancreatic cancer cells by inhibiting the
STAT3 signaling pathway.