Abstract
BackgroundProdigiosin (PG), a natural red pigment produced by numerous bacterial species, has been a eye-catching research point in recent years for its anticancer activity. However, the role of PG in the cancer biology of cholangiocarcinoma (CCA) remains vague.MethodsThe proliferation of CCA cells was detected by Cell Counting Kit-8(CCK-8), Colony formation assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was evaluated by flow cytometry assay and western blot assay. The effects of PG or SNAREs on cell autophagy were measured by autophagy flux assay and western blot assay. Xenograft mouse models were used to assess the role of PG in CCA cells in vivo.ResultsPG could inhibit the proliferation and viability of CCA cells in a concentration- and time-dependent manner via suppressing the late stage of autophagy. Mechanistically, PG inhibits the fusion of autophagosomes and lysosomes by blocking STX17 and SNAP29, components of soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNAREs)complex. When STX17 and SNAP29 were overexpressed, the inhibitory effect of PG on CCA cells autophagy was relieved. In addition, PG showed obvious inhibitory effects on cancer cell viability but no toxic effects on organs in xenotransplantation models.ConclusionTaken together, our results demonstrated that PG inhibits CCA cell proliferation via suppressing SNAREs-dependent autophagy, implying that PG could be a potential chemotherapy drug for advanced CCA.
Highlights
Cholangiocarcinoma (CCA)is a malignancy originating from biliary epithelial cells
We find that inhibiting autophagy leads to the suppression of proliferation capacity in CCA cells
PG promotes apoptosis by inhibiting the cellular activity of HuCCT‐1 and TFK‐1 cells To evaluate whether PG inhibits cell proliferation in the CCA cell lines, CCK-8 assay was employed to detect the cell survival rate
Summary
Cholangiocarcinoma (CCA)is a malignancy originating from biliary epithelial cells. Zheng et al Cancer Cell International (2021) 21:658 tolerance for side effects and poor treatment efficacy makes it far beyond satisfactory [6]; Recent studies have shown that natural products have certain applicable value in the prevention and treatment of cancer [7]. Prodigiosin (PG) is a general term for a class of natural red pigments, which is a biologically active secondary metabolite produced by actinomycetes, Serratia marcescens, or Pseudomona [8]. PG was shown to exhibit favorable biological activities in anti-bacterial [9], and anti-tumor activities, which has been proven to be an effective apoptotic agent for colon cancer, and lung cancer [10, 11]. Prodigiosin (PG), a natural red pigment produced by numerous bacterial species, has been a eyecatching research point in recent years for its anticancer activity. The role of PG in the cancer biology of cholangiocarcinoma (CCA) remains vague
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
