Antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents on human pancreatic cancer multicellular spheroids.
Devil's club (DC, Oplopanax horridus) is an important medicinal herb of the Pacific Northwest which has significant antiproliferation activity against a variety of human tumor cell lines in vitro. This study compared the antiproliferation activity of DC extract alone, and in combination with chemotherapeutic agents gemcitabine (GEM), cisplatin (CDDP), and paclitaxel (PTX) on human pancreatic cancer PANC-1 3D spheroids and 2D monolayer cells. 3D tumor spheroids were prepared with a rotary cell culture system. PANC-1 3D spheroids were significantly more resistant to killing by DC extract, GEM and PTX compared to 2D cells, with IC50 levels closer to that observed in vivo. DC extract significantly enhanced the antiproliferation activity of CDDP and GEM at some concentrations. The bioactive compound identified as a polyacetylene showed strong antiproliferation activity against PANC-1 2D cells and 3D spheroids with IC50 at 0.73±0.04 and 3.15±0.16μM, respectively. 3D spheroids and 2D cells differentially expressed a number of apoptosis related genes. Cell cycle analysis showed that the proportion of cells in S phase was increased and in G2/M phase reduced in 3D spheroids compared to 2D cells. DC extract can potentially be used to enhance the activity of chemotherapeutic agents against pancreatic cancer cells. Use of 3D spheroid model for screening of natural products can potentially increase the efficiency in discovering in vivo bioactive compounds.
Department of Pathology and Laboratory Medicine, Child and Family Research Institute, University of British Columbia, Canada. Electronic address: jtai@mail.ubc.ca.
J
J
Tai
Department of Surgery, University of British Columbia, Canada.
S S C
SS
Cheung
Department of Surgery, University of British Columbia, Canada.
D
D
Ou
Department of Surgery, University of British Columbia, Canada.
G L
GL
Warnock
Forensic Science Center, British Columbia Institute of Technology, Canada.
D
D
Hasman
D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification* / Q000627:therapeutic use; D017209:Apoptosis; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D028002:Oplopanax / Q000737:chemistry*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000627:therapeutic use*; D010946:Plants, Medicinal / Q000737:chemistry; D020543:Proteome; D018874:Spheroids, Cellular
D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D020543:Proteome
3D spheroid; Antiproliferation; Antitumor agents; Human pancreatic cancer cell line; North American herbal medicine; Oplopanax horridus