Calycosin induces apoptosis via p38‑MAPK pathway‑mediated activation of the mitochondrial apoptotic pathway in human osteosarcoma 143B cells. 2020

Wei Tian, and Zhi-Wei Wang, and Bao-Ming Yuan, and Yong-Ge Bao
Department of Orthopedics, Affiliated Hospital of Inner Mongolia University for The Nationalities, Tongliao, Inner Mongolia 028007, P.R. China.

Previous studies have demonstrated that calycosin is a natural phytoestrogen with a similar structure to estrogen, which can inhibit cell proliferation and induce apoptosis in a variety of tumors. Calycosin exerts potential pharmacological effects on osteosarcoma cells by inducing apoptosis. The aim of the present study was to elucidate the specific molecular mechanism of calycosin‑induced apoptosis in osteosarcoma cells. Cell proliferation was determined by an MTT assay. Annexin V/PI and JC‑1 staining were used to detect apoptosis and mitochondrial dysfunction, respectively, by flow cytometry. Western blot analysis was used to detect the expression of caspases or mitochondrial proteins. The results revealed that calycosin reduced the cell viability of human osteosarcoma 143B cells, induced apoptosis and increased the loss of mitochondrial membrane potential (MMP). In addition, calycosin increased the expression of the proapoptotic antiapoptotic proteins cleaved caspase‑3, cleaved caspase‑9, cleaved poly(ADP‑ribose) polymerase and Bcl‑2‑associated X protein (Bax), and decreased the expression of the antiapoptotic proapoptotic protein B‑cell lymphoma‑2 (Bcl‑2), thus altering the Bax/Bcl‑2 ratio. In addition, the expression levels of cytochrome c were markedly decreased in the mitochondria and increased in the cytoplasm following calycosin treatment. Furthermore, calycosin treatment induced p38‑mitogen‑activated protein kinase (MAPK) phosphorylation, whereas the p38‑MAPK inhibitor BIRB 796 markedly reversed cell viability, apoptosis and loss of MMP in 143B cells. These results suggested that calycosin inhibited osteosarcoma 143B cell growth via p38‑MAPK regulation of mitochondrial‑dependent intrinsic apoptotic pathways.

UI MeSH Term Description Entries
D007529 Isoflavones 3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position. 3-Benzylchroman-4-One,3-Benzylidene-4-Chromanone,Homoisoflavone,Homoisoflavones,Isoflavone,Isoflavone Derivative,3-Benzylchroman-4-Ones,3-Benzylidene-4-Chromanones,Isoflavone Derivatives,3 Benzylchroman 4 One,3 Benzylchroman 4 Ones,3 Benzylidene 4 Chromanone,3 Benzylidene 4 Chromanones,Derivative, Isoflavone,Derivatives, Isoflavone
D008928 Mitochondria Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed) Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D001859 Bone Neoplasms Tumors or cancer located in bone tissue or specific BONES. Bone Cancer,Cancer of Bone,Cancer of the Bone,Neoplasms, Bone,Bone Neoplasm,Neoplasm, Bone
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012516 Osteosarcoma A sarcoma originating in bone-forming cells, affecting the ends of long bones. It is the most common and most malignant of sarcomas of the bones, and occurs chiefly among 10- to 25-year-old youths. (From Stedman, 25th ed) Sarcoma, Osteogenic,Osteogenic Sarcoma,Osteosarcoma Tumor,Osteogenic Sarcomas,Osteosarcoma Tumors,Osteosarcomas,Sarcomas, Osteogenic,Tumor, Osteosarcoma,Tumors, Osteosarcoma
D015972 Gene Expression Regulation, Neoplastic Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue. Neoplastic Gene Expression Regulation,Regulation of Gene Expression, Neoplastic,Regulation, Gene Expression, Neoplastic
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines
D048051 p38 Mitogen-Activated Protein Kinases A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens. Mitogen-Activated Protein Kinase p38,p38 Mitogen-Activated Protein Kinase,p38 MAP Kinase,p38 MAPK,p38 Protein Kinase,p38 SAPK,MAP Kinase, p38,MAPK, p38,Mitogen Activated Protein Kinase p38,Protein Kinase, p38,p38 Mitogen Activated Protein Kinase,p38 Mitogen Activated Protein Kinases

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