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PP-32

Investigation of the anticancer effects and molecular mechanisms of the

calycosin derivative, Cpd49-1, in triple-negative breast cancer

1
Yi-Chen Li, Po-Chen Chu* ,1

1 Department of Cosmeceutics and Graduate Institute of Cosmeceutics, China Medical
University, Taichung 406040, Taiwan
* E-mail: chupc@mail.cmu.edu.tw

Abstract
Triple-negative breast cancer (TNBC), characterized by the highest recurrence rate and the
poorest prognosis, is the most aggressive subtype among all breast cancers. Although various
therapeutic strategies have been developed for breast cancer, the lack of effective targetable
proteins in TNBC limits treatment options. Calycosin, a functional phytoestrogen isoflavone
that can be isolated from various plants and Chinese herbs, such as Astragalus membranaceus,
Styphnolobium japonicum, and Thermopsis lanceolata, has been shown to exhibit anti-cancer
activity in multiple cancer models. However, the low bioavailability limits its clinical
applicability. In this study, we have developmented and compared the anti-cancer potency of
two calycosin-derived compounds, Cpd49-1 and Cpd49-2, in TNBC cells. Experimental results
revealed that Cpd49-1 exhibited stronger cytotoxic effects against TNBC cells than Cpd49-2.
Therefore, subsequent investigations focused on elucidating the mechanism of action of Cpd49-
1 in TNBC cells. Our findings showed that Cpd49-1 significantly inhibited both the migration
and proliferation of TNBC cells, as well as the growth of cancer stem cells. Moreover, Cpd49-
1 was found to suppress STAT3 signaling, supporting its potential as a STAT3-targeted
therapeutic candidate for TNBC.

Keywords: Triple negative breast cancer; STAT3 signaling; Calycosin; Breast cancer stem cells