Novel Mechanistic Insight into the Anticancer Activity of Cucurbitacin D against Pancreatic Cancer (Cuc D Attenuates Pancreatic Cancer)

Cells

Parvez Khan¹  FathiT. Halaweish²  Neeraj Chauhan³  MuraliM. Yallapu³  Sonam Kumari³  Sheema Khan³  SubhashC. Chauhan³  Bhavin Chauhan³  Meena Jaggi³  Mohammed Sikander³  Shabnam Malik³ 

[1] Center for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India;Department of Chemistry and Biochemistry, South Dakota State University, Brookings, SD 57007, USA;Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, TN 38163, USA;

关键词: pancreatic cancer;    cucurbitacin d;    mucin;    mir-145 and muc13;   

DOI  :  10.3390/cells9010103

来源: DOAJ

【 摘 要 】

Pancreatic cancer (PanCa) is one of the leading causes of death from cancer in the United States. The current standard treatment for pancreatic cancer is gemcitabine, but its success is poor due to the emergence of drug resistance. Natural products have been widely investigated as potential candidates in cancer therapies, and cucurbitacin D (Cuc D) has shown excellent anticancer properties in various models. However, there is no report on the therapeutic effect of Cuc D in PanCa. In the present study, we investigated the effects of the Cuc D on PanCa cells in vitro and in vivo. Cuc D inhibited the viability of PanCa cells in a dose and time dependent manner, as evident by MTS assays. Furthermore, Cuc D treatment suppressed the colony formation, arrest cell cycle, and decreased the invasion and migration of PanCa cells. Notably, our findings suggest that mucin 13 (MUC13) is down-regulated upon Cuc D treatment, as demonstrated by Western blot and qPCR analyses. Furthermore, we report that the treatment with Cuc D restores miR-145 expression in PanCa cells/tissues. Cuc D treatment suppresses the proliferation of gemcitabine resistant PanCa cells and inhibits RRM1/2 expression. Treatment with Cuc D effectively inhibited the growth of xenograft tumors. Taken together, Cuc D could be utilized as a novel therapeutic agents for the treatment/sensitization of PanCa.

【 授权许可】

Unknown