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J Cancer Metastasis Treat 2020;6:5 I http://dx.doi.org/10.20517/2394-4722.2020.13 Page 19 of 38

skin. Consistent with these results, we also found that silibinin strongly attenuates UVB-induced BMP-2
expression and DNA damage in Ptch+/− mouse skin ex vivo. Regarding BCC formation, silibinin treatment
inhibited UVB-induced microscopic BCC formation in Ptch+/− mice; microscopic tumor number and size
were reduced by 73% and 84%, respectively. Together, our results suggest a possible role of BMP-2 in early
stages of BCC development and that silibinin plausibly acts through BMP-2 to inhibit microscopic BCC
formation.

Conclusion: Our current findings in BCC model, together with previous studies in SCC model, suggest that
silibinin could be a multi-target agent capable of being a chemopreventive agent for both types of NMSCs.

26. A novel sulforaphane-regulated gene network in prevention of breast cancer-induced

osteolytic bone resorption

Shivendra V. Singh

Department of Pharmacology & Chemical Biology, and UPMC Hillman Cancer Center, University of
Pittsburgh, Pittsburgh, PA 15260, USA.

Bone is the most preferred site for colonization of metastatic breast cancer cells for each subtype of
the disease. The standard of therapeutic care for breast cancer patients with bone metastasis include
bisphosphonates (e.g., zoledronic acid), which have poor oral bioavailability, and a humanized antibody
(denosumab). However, these therapies are palliative and a subset of patients still develop new bone
lesions and/or experience serious adverse effects. Therefore, a safe and orally bioavailable intervention for
prevention/therapy of osteolytic bone resorption is still a clinically unmet need. This study demonstrates
prevention of breast cancer-induced bone resorption by a small molecule (sulforaphane, SFN) that is safe
clinically and orally bioavailable. in vitro osteoclast differentiation was inhibited in a dose-dependent
manner upon addition of conditioned media from SFN-treated breast cancer cells representative of
different subtypes. Targeted microarray coupled with interrogation of TCGA dataset revealed a novel SFN-
regulated gene signature involving cross-regulation of runt-related transcription factor 2 (RUNX2) and
nuclear factor-κB and their downstream effectors. Both RUNX2 and p65/p50 expression were higher in
human breast cancer tissues compared to normal mammary tissue. RUNX2 was recruited at the promotor
of NFKB1. Inhibition of osteoclast differentiation by SFN was augmented by doxycycline-inducible stable
knockdown of RUNX2. Oral SFN administration significantly increased the percentage of bone volume/
total volume of affected bones in the intracardiac MDA-MB-231-Luc model, indicating in vivo suppression
of osteolytic bone resorption by SFN. These results indicate that SFN is a novel inhibitor of breast cancer-
induced osteolytic bone resorption in vitro and in vivo. These findings necessitate clinical investigations to
determine the effect of SFN administration on osteolytic bone resorption in women with metastatic breast
cancer. This study was supported by grant CA225716 awarded by the National Cancer Institute.

27. Targeting of TM4SF5-mediated regulation of metabolic functions to overcome hepatic
cancer

Jung Weon Lee

College of Pharmacy, Seoul National University, Seoul 08826, South Korea.

Background and aim: Liver is an organ that can metabolize diverse nutrients and its cancers show arginine
auxotroph, which involves arginine delivery from extracellular diet sources and lysosomal protein