Abstract
Background
Thyroid carcinoma (TC) is the most common malignant tumor of the endocrine system. Phellinus linteus polysaccharide (PLP) physiologically acts as a suitable anti-tumor molecule. In this study, for the first time, we systematically investigated the anti-tumor activity of PLP in TC, aiming to promote the application of PLP in TC treatment.
Methods and results
TPC-1 and SW579 cells were treated with or without PLP. After treatment, MTT and EdU proliferation assays were performed to detect cell growth. Cell cycle was analyzed using flow cytometry. JC-1 staining was used to track change of mitochondrial membrane potential (MMP). Apoptotic cells were stained with annexin V-fluorescein isothiocyanate/propidium iodide and subsequently analyzed using flow cytometry. mCherry-GFP-LC3 was overexpressed in TC cells by lentiviral technology and the autophagosome was observed using confocal laser scanning microscope. Transwell migration and Matrigel invasion assays were performed to elucidate cell metastasis. Finally, underlying molecular mechanisms were investigated using RT-qPCR and western blotting. PLP inhibited cell growth in TC cells, which was attributable to the PLP-induced arrest at G0/G1 phase of cell cycle. PLP decreased the MMP, induced cell apoptosis, and promoted mitochondrial autophagy and endoplasmic reticulum autophagy. Furthermore, PLP may promote cell apoptosis via nuclear factor kappa-B pathway. In addition, PLP also inhibited cell migration and invasion through modulating the expression of epithelial–mesenchymal transition molecules such as E-cadherin, N-cadherin, and Vimentin
Conclusions
PLP exhibits notable anti-tumor activity in TC cells and may be used in TC treatment.
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Data availability
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Code availability
Not applicable.
References
M Al-Jundi S Thakur S Gubbi J Klubo-Gwiezdzinska 2020 Novel targeted therapies for metastatic thyroid cancera comprehensive review Cancers (Basel) 12 8 2104
Y Bai K Kakudo CK Jung 2020 Updates in the pathologic classification of thyroid neoplasms: a review of the world health organization classification Endocrinol Metab (Seoul) 35 696 715
X Zhang L Liu X Deng 2019 MicroRNA 483–3p targets Pard3 to potentiate TGF-β1-induced cell migration, invasion, and epithelial-mesenchymal transition in anaplastic thyroid cancer cells Oncogene 38 699 715
S Li HY Zhang ZX Du 2016 Induction of epithelial-mesenchymal transition (EMT) by Beclin 1 knockdown via posttranscriptional upregulation of ZEB1 in thyroid cancer cells Oncotarget 7 70364 70377
WY Lee KF Hsu TA Chiang CJ Chen 2015 Phellinus linteus extract induces autophagy and synergizes with 5-fluorouracil to inhibit breast cancer cell growth Nutr Cancer 67 275 284
D Sliva A Jedinak J Kawasaki K Harvey V Slivova 2008 Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling Br J Cancer 98 1348 1356
M-R Shin JH Lee JA Lee 2021 Immunomodulatory and anti-inflammatory effects of Phellinus linteus mycelium BMC complement med and ther 21 269 269
Y Liu C Wang J Li Y Mei Y Liang 2019 Hypoglycemic and hypolipidemic effects of phellinus linteus mycelial extract from solid-state culture in a rat model of type 2 diabetes Nutrients 11 2 296
Y Chai G Wang L Fan M Zhao 2016 A proteomic analysis of mushroom polysaccharide-treated HepG2 cells Sci Rep 6 23565 23565
KS Song SM Cho JH Lee 1995 B-lymphocyte-stimulating polysaccharide from mushroom Phellinus linteus Chem Pharm Bull (Tokyo) 43 2105 2108
JW Lee SJ Baek YS Kim 2008 submerged culture of Phellinus linteus for mass production of polysaccharides Mycobiology 36 178 182
W Gao W Wang W Sun M Wang N Zhang S Yu 2017 Antitumor and immunomodulating activities of six Phellinus igniarius polysaccharides of different origins Exp Ther Med 14 4627 4632
D Li X Cheng W Zheng J Chen 2020 Glucosamine-6-phosphate isomerase 1 promotes tumor progression and indicates poor prognosis in hepatocellular carcinoma Cancer Manag Res 12 4923 4935
X Xu S Zheng 2020 MiR-887-3p Negatively regulates STARD13 and promotes pancreatic cancer progression Cancer Manag Res 12 6137 6147
S Zhong DF Ji YG Li TB Lin ZQ Lv HP Chen 2013 Activation of P27kip1-cyclin D1/E-CDK2 pathway by polysaccharide from Phellinus linteus leads to S-phase arrest in HT-29 cells Chem Biol Interact 206 222 229
Y Li Q Luo L Yuan 2012 JNK-dependent Atg4 upregulation mediates asperphenamate derivative BBP-induced autophagy in MCF-7 cells Toxicol Appl Pharmacol 263 21 31
T Ikekawa M Nakanishi N Uehara G Chihara F Fukuoka 1968 Antitumor action of some Basidiomycetes, especially Phllinus linteus Gan 59 155 157
T Sasaki Y Arai T Ikekawa G Chihara F Fukuoka 1971 Antitumor polysaccharides from some polyporaceae, Ganoderma applanatum (Pers.) Pat and Phellinus linteus (Berk. et Curt) Aoshima Chem Pharm Bull (Tokyo) 19 821 826
D Duff A Long 2017 Roles for RACK1 in cancer cell migration and invasion Cell Signal 35 250 255
V Mittal 2018 Epithelial mesenchymal transition in tumor metastasis Annu Rev Pathol 13 395 412
MR Haymart NH Esfandiari MT Stang JA Sosa 2017 Controversies in the management of low-risk differentiated thyroid cancer Endocr Rev 38 351 378
D Rusinek E Chmielik J Krajewska 2017 Current advances in thyroid cancer management are we ready for the epidemic rise of diagnoses? Int J Mol Sci 18 1817
KS Song G Li JS Kim 2011 Protein-bound polysaccharide from Phellinus linteus inhibits tumor growth, invasion, and angiogenesis and alters Wnt/β-catenin in SW480 human colon cancer cells BMC Cancer 11 307
TL Lu GJ Huang TJ Lu 2009 Hispolon from Phellinus linteus has antiproliferative effects via MDM2-recruited ERK1/2 activity in breast and bladder cancer cells Food Chem Toxicol 47 2013 2021
YG Li DF Ji S Zhong 2013 Polysaccharide from Phellinus linteus induces S-phase arrest in HepG2 cells by decreasing calreticulin expression and activating the P27kip1-cyclin A/D1/E-CDK2 pathway J Ethnopharmacol 150 187 195
SL Liu Z Liu LD Zhang 2017 GSK3β-dependent cyclin D1 and cyclin E1 degradation is indispensable for NVP-BEZ235 induced G0/G1 arrest in neuroblastoma cells Cell Cycle 16 2386 2395
E Aleem H Kiyokawa P Kaldis 2005 Cdc2-cyclin E complexes regulate the G1/S phase transition Nat Cell Biol 7 831 836
Y Guan Y Li G Zhao Y Li 2018 HMGB1 Promotes the starvation-induced autophagic degradation of α-synuclein in SH-SY5Y cells Atg 5-dependently Life Sci 202 1 10
O Adams B Dislich S Berezowska 2016 Prognostic relevance of autophagy markers LC3B and p62 in esophageal adenocarcinomas Oncotarget 7 39241 39255
O Adams FA Janser B Dislich 2018 A specific expression profile of LC3B and p62 is associated with nonresponse to neoadjuvant chemotherapy in esophageal adenocarcinomas PLoS ONE 13 e0197610
M Komatsu S Waguri M Koike 2007 Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice Cell 131 1149 1163
JY Chang HS Yi HW Kim M Shong 2017 Dysregulation of mitophagy in carcinogenesis and tumor progression Biochim Biophys Acta Bioenergy 1858 633 640
S Deegan S Saveljeva AM Gorman A Samali 2013 Stress-induced self-cannibalism: on the regulation of autophagy by endoplasmic reticulum stress Cell Mol Life Sci 70 2425 2441
Z Hamivand G Haddadi R Fardid 2018 Expression of bax and Bcl2 genes in peripheral blood lymphocytes of patients with differentiated thyroid cancer J Med Phys 43 41 45
L Wan D Zhang J Zhang L Ren 2018 TT-1, an analog of melittin, triggers apoptosis in human thyroid cancer TT cells via regulating caspase, Bcl-2 and Bax Oncol Lett 15 1271 1278
I Pastushenko C Blanpain 2019 EMT Transition states during tumor progression and metastasis Trends Cell Biol 29 212 226
M Saitoh 2018 Involvement of partial EMT in cancer progression J Biochem 164 257 264
Acknowledgements
We are very grateful to the Project of Scientific Research Foundation of Chinese Medicine (Grant Number 2020ZA007) for its financial support.
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The study was supported by the Project of Scientific Research Foundation of Chinese Medicine (Grant Number 2020ZA007).
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KY and YX conceived and designed the study. YX critically revised the manuscript. KY and ZT performed the experiments, analyzed the data. KY drafted the manuscript. All authors read and approved the final manuscript.
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Yu, K., Tan, Z. & Xin, Y. Systematic evaluation of the anti-tumor effect of Phellinus linteus polysaccharide in thyroid carcinoma in vitro. Mol Biol Rep 49, 2785–2793 (2022). https://doi.org/10.1007/s11033-021-07090-6
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DOI: https://doi.org/10.1007/s11033-021-07090-6