BRM270 Inhibits the Proliferation of CD44 Positive Pancreatic Ductal Adenocarcinoma Cells via Downregulation of Sonic Hedgehog Signaling

Do Luong Huynh; Hyebin Koh; Nisansala Chandimali; Jiao Jiao Zhang; Nameun Kim; Tae Yoon Kang; Mrinmoy Ghosh; Meeta Gera; Yang-Ho Park; Taeho Kwon; Dong Kee Jeong

doi:10.1155/2019/8620469

BRM270 Inhibits the Proliferation of CD44 Positive Pancreatic Ductal Adenocarcinoma Cells via Downregulation of Sonic Hedgehog Signaling

Evid Based Complement Alternat Med. 2019 Feb 24:2019:8620469. doi: 10.1155/2019/8620469. eCollection 2019.

Authors

Do Luong Huynh¹, Hyebin Koh¹, Nisansala Chandimali¹, Jiao Jiao Zhang^{1

2}, Nameun Kim^{1

3}, Tae Yoon Kang¹, Mrinmoy Ghosh^{1

4}, Meeta Gera¹, Yang-Ho Park⁵, Taeho Kwon^{1

6}, Dong Kee Jeong¹

Affiliations

¹ Laboratory of Animal Genetic Engineering and Stem Cell Biology, Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Republic of Korea.
² Chongqing Key Laboratory of Forage and Herbivore, College of Animal Science and Technology, Southwest University, Chongqing 400715, China.
³ Jeju Special Self-Governing Province Livestock Promotion Agency, 13 Chuksanmaeul-gil, Jeju 63078, Republic of Korea.
⁴ Department of Biotechnology, Division of Research and Development, Lovely Professional University, Punjab 144411, India.
⁵ BRM Institute, Seoul 01756, Republic of Korea.
⁶ Primate Resource Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Jeongeup-si, Jeonbuk 56216, Republic of Korea.

Abstract

Pancreatic cancer has a poor survival rate as compared to other types of cancer. Surface marker CD44 plays important role in epithelial-mesenchymal transition and cancer stem cell phenotype. Therefore, targeting CD44 positive pancreatic cancer cells might enhance therapies effectiveness. Our previous studies indicated the antitumorigenesis effect of BRM270 in osteosarcoma, lung cancer, and glioblastoma; however there is no evidence on BRM270 impacts on pancreatic cancer growth. In this study, we investigated the effect of BRM270 on the isolated CD44 positive pancreatic ductal adenocarcinoma cells (CD44⁺ PDAC). Results showed that CD44 positive cells undergo apoptosis induced by BRM270. Moreover, BRM270 also inhibits stemness and metastasis traits in CD44⁺ PDAC via Sonic hedgehog signaling pathway and SALL4 expression. In vivo study indicated that tumor growth derived from CD44⁺ PDAC was suppressed as daily uptake by BRM270 5 mg/kg. These data suggest the alternative approach in antipancreatic tumorigenesis via herbal plants extract and selectively targeting CD44⁺ PDAC cells in tumor.