Convallatoxin suppresses osteosarcoma cell proliferation, migration, invasion, and enhances osteogenic differentiation by downregulating parathyroid hormone receptor 1 (PTHR1) expression and inactivating Wnt/β-catenin pathway

References

• Yao Q, Li Y, Pei Y, et al. Long non-coding RNA taurine up regulated 1 promotes osteosarcoma cell proliferation and invasion through upregulating Ezrin expression as a competing endogenous RNA of micro RNA-377-3p. Bioengineered. 2022;13(1):1767–1778.
   PubMed Web of Science ®Google Scholar
• Luo X, Chen J, Song WX, et al. Osteogenic BMPs promote tumor growth of human osteosarcomas that harbor differentiation defects. Lab Invest. 2008;88(12):1264–1277.
   PubMed Web of Science ®Google Scholar
• Ferrari S, Ruggieri P, Cefalo G, et al. Neoadjuvant chemotherapy with methotrexate, cisplatin, and doxorubicin with or without ifosfamide in nonmetastatic osteosarcoma of the extremity: an Italian sarcoma group trial ISG/OS-1. J Clin Oncol. 2012;30(17):2112–2118.
   PubMed Web of Science ®Google Scholar
• Haghiralsadat F, Amoabediny G, Naderinezhad S, et al. Codelivery of doxorubicin and JIP1 siRNA with novel EphA2-targeted PEGylated cationic nanoliposomes to overcome osteosarcoma multidrug resistance. Int J Nanomedicine. 2018;13:3853–3866.
   PubMed Web of Science ®Google Scholar
• Zhang QH, Hu QX, Xie D, et al. Ganoderma lucidum exerts an anticancer effect on human Osteosarcoma cells via suppressing the Wnt/β-catenin signaling pathway. Integr Cancer Ther. 2019;18:1534735419890917.
   Web of Science ®Google Scholar
• Kumavath R, Paul S, Pavithran H, et al. Emergence of cardiac glycosides as potential drugs: Current and future scope for cancer therapeutics. Biomolecules. 2021;11(9):1275.
   PubMed Web of Science ®Google Scholar
• Reddy D, Kumavath R, Ghosh P, et al. Lanatoside C induces G2/M cell cycle arrest and suppresses cancer cell growth by attenuating MAPK, Wnt, JAK-STAT, and PI3K/AKT/mTOR signaling pathways. Biomolecules. 2019;9(12):792.
   PubMed Web of Science ®Google Scholar
• Morimoto M, Tatsumi K, Yuui K, et al. Convallatoxin, the primary cardiac glycoside in lily of the valley (convallaria majalis), induces tissue factor expression in endothelial cells. Vet Med Sci. 2021;7(6):2440–2444.
   PubMed Web of Science ®Google Scholar
• Zhang ZH, Li MY, Wang Z, et al. Convallatoxin promotes apoptosis and inhibits proliferation and angiogenesis through crosstalk between JAK2/STAT3 (T705) and mTOR/STAT3 (S727) signaling pathways in colorectal cancer. Phytomedicine. 2020;68:153172.
   PubMed Web of Science ®Google Scholar
• Anderson SE, Barton CE. The cardiac glycoside convallatoxin inhibits the growth of colorectal cancer cells in a p53-independent manner. Mol Genet Metab Rep. 2017;13:42–45.
   PubMed Web of Science ®Google Scholar
• Kaushik V, Azad N, Yakisich JS, et al. Antitumor effects of naturally occurring cardiac glycosides convallatoxin and peruvoside on human ER+ and triple-negative breast cancers. Cell Death Discov. 2017;3(1):17009.
   PubMed Web of Science ®Google Scholar
• Goltzman D. Studies on the mechanisms of the skeletal anabolic action of endogenous and exogenous parathyroid hormone. Arch Biochem Biophys. 2008;473(2):218–224.
   PubMed Web of Science ®Google Scholar
• Pitarresi JR, Norgard RJ, Chiarella AM, et al. PTHrP drives pancreatic cancer growth and metastasis and reveals a new therapeutic vulnerability. Cancer Discov. 2021;11(7):1774–1791.
   PubMed Web of Science ®Google Scholar
• Qu Z, Li S. Long noncoding RNA LINC01278 favors the progression of osteosarcoma via modulating miR-133a-3p/PTHR1 signaling. J Cell Physiol. 2020. DOI:10.1002/jcp.29582
   Web of Science ®Google Scholar
• Ho PW, Goradia A, Russell MR, et al. Knockdown of PTHR1 in osteosarcoma cells decreases invasion and growth and increases tumor differentiation in vivo. Oncogene. 2015;34(22):2922–2933.
   PubMed Web of Science ®Google Scholar
• Li S, Dong Y, Wang K, et al. Transcriptomic analyses reveal the underlying pro-malignant functions of PTHR1 for osteosarcoma via activation of Wnt and angiogenesis pathways. J Orthop Surg Res. 2017;12(1):168.
   PubMed Web of Science ®Google Scholar
• Lin YC, Haas A, Bufe A, et al. Wnt10b-GSK3β-dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells. Life Sci Alliance. 2021;4(1):e202000855.
   PubMed Web of Science ®Google Scholar
• Han YL, Luo D, Habaxi K, et al. COL5A2 Inhibits the TGF-β and Wnt/β-Catenin signaling pathways to inhibit the invasion and metastasis of osteosarcoma. Front Oncol. 2022;12:813809.
   PubMed Web of Science ®Google Scholar
• Chu W, Cao L, Daokun G, et al. iNOS promotes the development of osteosarcoma via Wnt/β-catenin pathway. J Immunol Res. 2021;2021:4549221.
   PubMed Web of Science ®Google Scholar
• Shao S, Piao L, Wang J, et al. Tspan9 induces EMT and promotes osteosarcoma metastasis via activating FAK-Ras-ERK1/2 pathway. Front Oncol. 2022;12:774988.
   PubMed Web of Science ®Google Scholar
• Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods. 2001;25(4):402–408.
   PubMed Web of Science ®Google Scholar
• Lee J, Kang J-S, Nam LB, et al. Suppression of NRF2/ARE by convallatoxin sensitises A549 cells to 5-FU-mediated apoptosis. Free Radic Res. 2018;52(11–12):1416–1423.
   PubMed Web of Science ®Google Scholar
• Schneider NF, Geller FC, Persich L, et al. Inhibition of cell proliferation, invasion and migration by the cardenolides digitoxigenin monodigitoxoside and convallatoxin in human lung cancer cell line. Nat Prod Res. 2016;30(11):1327–1331.
   PubMed Web of Science ®Google Scholar
• Li S, Pei Y, Wang W, et al. Quercetin suppresses the proliferation and metastasis of metastatic osteosarcoma cells by inhibiting parathyroid hormone receptor 1. Biomed Pharmacother. 2019;114:108839.
   PubMed Web of Science ®Google Scholar
• Li S, Chen P, Zheng K, et al. β-Alanine mediated inhibition of PTHR1suppresses the proliferation, invasion and tumorigenesis in metastatic human osteosarcoma U2OS cells. Int J Biol Macromol. 2018;111:1255–1263.
   PubMed Web of Science ®Google Scholar