11-O-Galloyl Bergenin from Corylopsis coreanas Leaves Induces Autophagy and Apoptosis in Human Osteosarcoma

2021 ◽  
Vol 49 (08) ◽  
pp. 2017-2031
Author(s):  
Kyung-Ran Park ◽  
Yoon-Ju Kwon ◽  
Myounglae Cho ◽  
Il Keun Kwon ◽  
Jin Tae Hong ◽  
...  
Keyword(s):  
Annexin V ◽  
Mg63 Cell ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Boyden Chamber ◽  
Antitumor Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Induced Apoptosis

Osteosarcoma is the most common malignant bone-forming tumor, wherein most patients with high grade osteosarcomas are treated with chemotherapy. Despite this, survival for metastatic or relapsed osteosarcoma patients has remained at an overall 5-year survival rate of 20%. In particular, the extracts of Corylopsis coreana (Korean winter hazel), a cultivated woody plant in South Korea, have shown beneficial anti-inflammatory, anti-oxidative, anti-osteoclastic, and antihyperuricemic properties. Therefore, this study aimed to demonstrate the antitumor activities and underlying mechanism of 11-O-Galloyl bergenin (OGAL) isolated from Corylopsis coreanas leaves in human osteosarcoma cells. Herein, we found that OGAL inhibited MG63 cell proliferation and induced cellular apoptosis as evidenced by cleaved-PARP, cleaved-caspase 3, TUNEL-positive cells, and Annexin V-positive cells. Specifically, OGAL-induced apoptosis was accompanied by p53 and p21 upregulation, BAX expression, and decreased Bcl-2 and cdk2. Moreover, OGAL induced autophagy via AKT inactivation, LC3II upregulation, and MG63 cell autophagosome formation. OGAL-induced autophagy was also accompanied by increased p38 phosphorylation, whereas JNK and ERK1/2 activities were found to be unaffected upon examining the MAPK signaling pathway. Furthermore, wound healing and Boyden chamber assays showed that OGAL suppressed MG63 cell migration and invasion. Given these findings, this study provided evidence that OGAL has antitumor effects by apoptosis and autophagy enhancement through increased p53, AKT, and p38 signaling, suggesting that OGAL may be a potential therapeutic strategy for osteosarcoma treatment.

scholarly journals Licochalcone A-Induced Apoptosis Through the Activation of p38MAPK Pathway Mediated Mitochondrial Pathways of Apoptosis in Human Osteosarcoma Cells In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1441 ◽  
Author(s):  
Lin ◽  
Yang ◽  
Chiou ◽  
Hsieh ◽  
Wen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Osteosarcoma Cells ◽  
Antitumor Effects ◽  
Licochalcone A ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Background: Licochalcone A (LicA) is isolated from the roots of Glycyrrhiza glabra and possesses antitumor and anti-invasive activities against several tumor cells. However, the antitumor effects of LicA on human osteosarcoma cells have yet to be demonstrated either in vitro or in vivo. Methods: Cell viability was measured by MTT assay. Apoptosis and mitochondrial dysfunction were detected with Annexin V/PI staining and JC-1 staining by flow cytometry. The expressions of caspase- or mitochondrial-related proteins were demonstrated by western blotting. Antitumor effect of LicA on 143B xenograft mice in vivo. Results: LicA could inhibit cell proliferation and induce apoptosis in human osteosarcoma cells, as evidenced by a decrease in cell viability, loss of mitochondrial membrane potentials, and activation of caspases. LicA treatment substantially reduced the expression of Bcl-2 and Mcl-1 and increased the expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, and Bax in HOS and U2OS cells. Moreover, mitochondrial membrane potential and apoptosis suppression mediated by Z-VAD or tauroursodeoxycholic acid significantly reduced LicA-induced mitochondria-dependent apoptosis. The study also determined that LicA treatment induced p38MAPK phosphorylation, but siRNA-p38 or BIRB796 substantially reversed cell viability through the inhibition of mitochondria-dependent apoptosis pathways. Finally, an in vivo study revealed that LicA significantly inhibited 143B xenograft tumor growth. Conclusions: These findings demonstrate that LicA has antitumor activities against human osteosarcoma cells through p38MAPK regulation of mitochondria-mediated intrinsic apoptotic pathways in vitro and in vivo.

scholarly journals Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

2017 ◽  
Vol 44 (4) ◽  
pp. 1396-1410 ◽  
Author(s):  
Ying Liu ◽  
Yan Zhang ◽  
Jilong Zou ◽  
Lixin Yan ◽  
Xiufeng Yu ◽  
...  
Keyword(s):  
Cell Death ◽  
Morphological Changes ◽  
Annexin V ◽  
Beclin 1 ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Invasion And Metastasis ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Background/Aims: Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue. Although treatment effectiveness has improved, the OS survival rate has fluctuated in recent years. Andrographolide (AG) has been reported to have antitumor activity against a variety of tumors. Our aim was to investigate the effects and potential mechanisms of AG in human osteosarcoma. Methods: Cell viability and morphological changes were assessed by MTT and live/dead assays. Apoptosis was detected using Annexin V-FITC/PI double staining, DAPI, and caspase-3 assays. Autophagy was detected with mRFP-GFP-LC3 adenovirus transfection and western blot. Cell migration and invasion were detected by wound healing assay and Transwell® experiments. Results: AG dose-dependently reduced the viability of osteosarcoma cells. No increase in apoptosis was detected in AG-treated human OS MG-63 and U-2OS cells, and the pan-caspase inhibitor z-VAD did not attenuate AG-induced cell death. However, AG induced autophagy by suppressing PI3K/Akt/mTOR and enhancing JNK signaling pathways. 3-MA and Beclin-1 siRNA could reverse the cytotoxic effects of AG. In addition, AG inhibited the invasion and metastasis of OS, and this effect could be reversed with Beclin-1 siRNA. Conclusion: AG inhibits viability and induces autophagic death in OS cells. AG-induced autophagy inhibits the invasion and metastasis of OS.

scholarly journals Diallyl Disulfide Induces Apoptosis and Autophagy in Human Osteosarcoma MG-63 Cells through the PI3K/Akt/mTOR Pathway

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2665 ◽  
Author(s):  
Ziqi Yue ◽  
Xin Guan ◽  
Rui Chao ◽  
Cancan Huang ◽  
Dongfang Li ◽  
...  
Keyword(s):  
Annexin V ◽  
Mtor Pathway ◽  
Diallyl Disulfide ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
M Phase ◽  
Induced Apoptosis

Diallyl disulfide (DADs), a natural organic compound, is extracted from garlic and scallion and has anti-tumor effects against various tumors. This study investigated the anti-tumor activity of DADs in human osteosarcoma cells and the mechanisms. MG-63 cells were exposed to DADs (0, 20, 40, 60, 80, and 100 μM) for different lengths of time (24, 48, and 72 h). The CCK8 assay results showed that DADs inhibited osteosarcoma cell viability in a dose-and time-dependent manner. FITC-Annexin V/propidium iodide staining and flow cytometry demonstrated that the apoptotic ratio increased and the cell cycle was arrested at the G2/M phase as the DADs concentration was increased. A Western blot analysis was employed to detect the levels of caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and p62 as well as suppression of the mTOR pathway. High expression of LC3-II protein revealed that DADs induced formation of autophagosome. Furthermore, DADs-induced apoptosis was weakened after adding 3-methyladenine, demonstrating that the DADs treatment resulted in autophagy-mediated death of MG-63 cells. In addition, DADs depressed p-mTOR kinase activity, and the inhibited PI3K/Akt/mTOR pathway increased DADs-induced apoptosis and autophagy. In conclusion, our results reveal that DADs induced G2/M arrest, apoptosis, and autophagic death of human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

scholarly journals CLEFMA Activates the Extrinsic and Intrinsic Apoptotic Processes through JNK1/2 and p38 Pathways in Human Osteosarcoma Cells

Molecules ◽  
2019 ◽  
Vol 24 (18) ◽  
pp. 3280 ◽  
Author(s):  
Jia-Sin Yang ◽  
Renn-Chia Lin ◽  
Yi-Hsien Hsieh ◽  
Heng-Hsiung Wu ◽  
Geng-Chung Li ◽  
...  
Keyword(s):  
Annexin V ◽  
Synthetic Analog ◽  
Osteosarcoma Cells ◽  
Apoptotic Pathway ◽  
Term Survival ◽  
Anticancer Properties ◽  
Human Osteosarcoma ◽  
Effector Caspase ◽  
Human Osteosarcoma Cells ◽  
Induced Apoptosis

Due to the poor prognosis of metastatic osteosarcoma, chemotherapy is usually employed in the adjuvant situation to improve the prognosis and the chances of long-term survival. 4-[3,5-Bis(2-chlorobenzylidene)-4-oxo-piperidine-1-yl]-4-oxo-2-butenoic acid (CLEFMA) is a synthetic analog of curcumin and possesses anti-inflammatory and anticancer properties. To further obtain information regarding the apoptotic pathway induced by CLEFMA in osteosarcoma cells, microculture tetrazolium assay, annexin V-FITC/PI apoptosis staining assay, human apoptosis array, and Western blotting were employed. CLEFMA dose-dependently decreased the cell viabilities of human osteosarcoma U2OS and HOS cells and significantly induced apoptosis in human osteosarcoma cells. In addition to the effector caspase 3, CLEFMA significantly activated both extrinsic caspase 8 and intrinsic caspase 9 initiators. Moreover, CLEFMA increased the phosphorylation of extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal kinases (JNK)1/2 and p38. Using inhibitors of JNK (JNK-in-8) and p38 (SB203580), CLEFMA’s increases of cleaved caspases 3, 8, and 9 could be expectedly suppressed, but they could not be affected by co-treatment with the ERK inhibitor (U0126). Conclusively, CLEFMA activates both extrinsic and intrinsic apoptotic pathways in human osteosarcoma cells through JNK and p38 signaling. These findings contribute to a better understanding of the mechanisms responsible for CLEFMA’s apoptotic effects on human osteosarcoma cells.

scholarly journals Bioactivity and Apoptotic Efficacy of the Purified Terpenoid Extract from the Moss Brachythecium Buchananii (Hook.) A. Jaeger against MG 63 Cells

2020 ◽  
pp. 287-294
Author(s):  
Geetha Mohandas Greeshma ◽  
Gopal Sarayu Manoj ◽  
Kumaraswamy Murugan
Keyword(s):  
Cell Lines ◽  
Biological Effects ◽  
Mg63 Cell ◽  
Migration And Invasion ◽  
Antioxidant Enzyme System ◽  
Apoptotic Protein ◽  
Human Osteosarcoma Cells ◽  
Mg63 Cells ◽  
Caspase Cascade ◽  
Induced Apoptosis

Bryophytes are primitive non vascular plants. A little is explored regarding the medicinal effects of bryophytes on carcinoma. This study investigated the biological effects of purified terpenoids from Brachythecium buchananii on selected cell lines such as HeLa, MDAMB-231 and MG63 human osteosarcoma cells and also elucidating the regu­latory signaling pathways underlying the effects of terpenoids towards caspase cascade and the antioxidant enzyme system. The cell lines were treated with various concentrations of purified terpenoid extracts interms of evaluating viability (MTT assay). Interestingly, MG63 cell lines showed poor viability as compared to other ongo cells and was subjected to further molecular evaluations. Migration and invasion assay results using wound-healing and transwell assays, respectively reveal the pro-antimetastatic potential of the purified terpenoids from the moss. The flow cytometry study substantiated terpenoid induced apoptosis in MG63 cells. Cell cycle analysis revealed the significant increase in the number of cells arrested at the S growth phase. Terpenoid extract also displayed DNA fragmentation in the cells. Western blot analysis revealed the down regulation of the anti‑apoptotic proteins Bcl‑2, pro‑caspase 3 and over expression of the pro‑apoptotic protein Bax. In addition, the caspase cascade profile of the terpenoid extract substantiated their efficacy in tumour inhibition. Thus, the overall results confirmed the biological features of terpenoid induced apoptosis in the MG63 cells.

Effect of dual inhibition of the Src and insulin-like growth factor-1 receptor (IGF-1R) pathways on antitumor effects in prostate cancer (PCa).

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 21-21
Author(s):  
F. Dayyani ◽  
N. Parikh ◽  
J. H. Song ◽  
J. C. Araujo ◽  
J. M. Carboni ◽  
...  
Keyword(s):  
Annexin V ◽  
Parp Cleavage ◽  
Boyden Chamber ◽  
Antitumor Effects ◽  
Downstream Target ◽  
Control Shrna ◽  
Pc3 Cells ◽  
Dual Inhibition ◽  
And Migration ◽  
Induced Apoptosis

21 Background: The Src and IGF-1R axes are aberrantly activated in both PCa and the microenvironment of bone metastases. Dasatinib and BMS-754807 are clinically promising small molecule inhibitors with high potency against Src family kinases and IGF-1R, respectively. The aim of this study was to establish antitumor co-operativity by combining IGF-1R and Src blockade in a preclinical PCa model. Methods: LNCaP and PC3 cells were used as models for androgen-dependent and independent PCa, respectively. Inhibition of Src and IGF-1R pathways was accomplished by pharmacologic agents (dasatinib against Src and BMS-754807 against IGF-1R) as well as by shRNA. Serum IGF-1 levels were measured in patients (pts) with castration-resistant PCa (CRPC) treated with dasatinib and docetaxel in a phase II trial. Results: Src inhibition decreased proliferation of PCa cells, and migration in modified Boyden Chamber and wound assays. In contrast, IGF-1R blockade induced apoptosis (increased Sub-G1 fraction cells, Annexin-V(+) cells and PARP cleavage). Phosphorylation of Akt was partially inhibited by either drug alone and almost completely abrogated by the combination. Intraprostatic injection of shIGF-1R or shSrc PC3 cells in nude mice led to an 83% and 60% decrease in tumor size compared to control shRNA, respectively. In both cell lines, all observed antitumor effects were enhanced when dual blockade was used, relative to blocking the Src or IGF-1R pathway alone. In 9/19 (47%) pts with CRPC, treatment with dasatinib resulted in a compensatory increase of serum IGF-1 levels. Conclusions: Dual inhibition of Src and IGF-1R is effective and complementary in PCa, mediated, in part, through inhibition of the downstream target Akt. In about half of pts treated with dasatinib, an increase in soluble IGF-1 levels was observed, indicating there is a compensatory upregulation of survival pathways that might be abrogated by dual inhibition of Src and IGF-1R. The combination of dasatinib and BMS-754807 may be a rational therapeutic approach in PCa by blocking complementary processes of tumor growth and progression. [Table: see text]

scholarly journals Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chunyang Li ◽  
Shuangqing Yang ◽  
Huaqing Ma ◽  
Mengjia Ruan ◽  
Luyan Fang ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Underlying Mechanism ◽  
Tissue Growth ◽  
Migration And Invasion ◽  
Dependent Manner ◽  
Antitumor Effects ◽  
Siha Cells ◽  
Cervical Cancer Cells

Abstract Background Cervical cancer is a type of the most common gynecology tumor in women of the whole world. Accumulating data have shown that icariin (ICA), a natural compound, has anti-cancer activity in different cancers, including cervical cancer. The study aimed to reveal the antitumor effects and the possible underlying mechanism of ICA in U14 tumor-bearing mice and SiHa cells. Methods The antitumor effects of ICA were investigated in vivo and in vitro. The expression of TLR4/MyD88/NF-κB and Wnt/β-catenin signaling pathways were evaluated. Results We found that ICA significantly suppressed tumor tissue growth and SiHa cells viability in a dose-dependent manner. Also, ICA enhanced the anti-tumor humoral immunity in vivo. Moreover, ICA significantly improved the composition of the microbiota in mice models. Additionally, the results clarified that ICA significantly inhibited the migration, invasion capacity, and expression levels of TGF-β1, TNF-α, IL-6, IL-17A, IL-10 in SiHa cells. Meanwhile, ICA was revealed to promote the apoptosis of cervical cancer cells by down-regulating Ki67, survivin, Bcl-2, c-Myc, and up-regulating P16, P53, Bax levels in vivo and in vitro. For the part of mechanism exploration, we showed that ICA inhibits the inflammation, proliferation, migration, and invasion, as well as promotes apoptosis and immunity in cervical cancer through impairment of TLR4/MyD88/NF-κB and Wnt/β-catenin pathways. Conclusions Taken together, ICA could be a potential supplementary agent for cervical cancer treatment.

scholarly journals Beneficial Actions of Orostachys japonica and Its Compounds against Tumors via MAPK Signaling Pathways

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 555
Author(s):  
Soyoung Hur ◽  
Eungyeong Jang ◽  
Jang-Hoon Lee
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial To Mesenchymal Transition ◽  
Malignant Tumors ◽  
Treatment Options ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Antitumor Effects ◽  
Mesenchymal Transition ◽  
Perennial Plant

Tumors are one of the most life-threatening diseases, and a variety of cancer treatment options have been continuously introduced in order to overcome cancer and improve conventional therapy. Orostachys japonica (O. japonica), which is a perennial plant belonging to the genus Orostachys of the Crassulaceae family, has been revealed to exhibit pharmacological properties against various tumors in numerous studies. The present review aimed to discuss the biological actions and underlying molecular mechanisms of O. japonica and its representative compounds—kaempferol and quercetin—against tumors. O. japonica reportedly has antiproliferative, anti-angiogenic, and antimetastatic activities against various types of malignant tumors through the induction of apoptosis and cell cycle arrest, a blockade of downstream vascular endothelial growth factor (VEGF)-VEGFR2 pathways, and the regulation of epithelial-to-mesenchymal transition. In addition, emerging studies have highlighted the antitumor efficacy of kaempferol and quercetin. Interestingly, it was found that alterations of the mitogen-activated protein kinase (MAPK) signaling cascades are involved in the pivotal mechanisms of the antitumor effects of O. japonica and its two compounds against cancer cell overgrowth, angiogenesis, and metastasis. In summary, O. japonica could be considered a preventive and therapeutic medicinal plant which exhibits antitumor actions by reversing altered patterns of MAPK cascades, and kaempferol and quercetin might be potential components that can contribute to the efficacy and underlying mechanism of O. japonica.

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