Volume 21, Issue 4, 15 March 2014, Pages 506–514
Antiproliferation activity of Devil's club (Oplopanax horridus) and anticancer agents on human pancreatic cancer multicellular spheroids
Abstract
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 ± 0.16 μM, 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.
Graphical abstract
Keywords
- Oplopanax horridus;
- Human pancreatic cancer cell line;
- North American herbal medicine;
- 3D spheroid;
- Antiproliferation;
- Antitumor agents
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