Tea polyphenol decreased growth and invasion in human ovarian cancer cells

Tea polyphenols (TP) are functional substances present in tea, which is one of the most promising preventive agents for cancer. This study was carried out to analyze the effects of TP on the ovarian cancer cells and possible mechanisms involved. TP led to inhibition of cell growth in a time- and dose-dependent manner, and promoted entry into the apoptosis-phase of the cell cycle. TP also decreased the invasion of ovarian cancer cells in vitro. In addition, TP treatment upregulated the mRNA expressions rate of Bax/Bcl-2 and downregulated Cyclin D and MMP2 mRNA expressions. Taken together, our data highlight that TP could be a potential therapeutic strategy for ovarian cancer. These findings also suggested that oncogens are involved in the anti-cancer effects of TP.

Download Full-text

Evaluation of Silibinin-Loaded Microbubbles Combined with Ultrasound in Ovarian Cancer Cells: Cytotoxicity and Mechanisms

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/1871520621666210608101649 ◽

2021 ◽

Vol 21 ◽

Author(s):

Liguang Zhou ◽

Jing Liu ◽

Wen Meng ◽

Huawei Zhang ◽

Bo Chen

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Mechanical Vibration ◽

Cell Types ◽

Local Drug Delivery ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Western Blots

Background: The anticancer activity of silibinin (SB) has been demonstrated in various cancer cell types. However, its low solubility and poor bioavailability limit its clinical potential in biomedical applications. Microbubbles in combination with ultrasound are promising vehicles for local drug delivery. Objective: The present study determined the antitumour effects and molecular mechanism of silibinin-loaded microbubbles (SBMBs) in combination with ultrasound on ovarian cancer in vitro. Methods: SBMBs were prepared using mechanical vibration. The viability of A2780 cells was determined using the MTT assay. Flow cytometry was performed to detect cell apoptosis and the cell cycle. The expression of receptor tyrosine kinase (RTK)-associated downstream proteins was detected using multiplex assays and Western blots. Results: The present study designed and synthesized SBMBs. SBMBs in combination with ultrasound decreased A2780 cell viability in a dose- and time-dependent manner. The half maximal inhibitory concentration (IC50) showed that the cytotoxicity of the SBMBs was approximately 1.5 times greater than that of the SB in A2780 cells. SBMBs in combination with ultrasound resulted in significantly higher apoptosis efficiency compared to the SB group, and the SBMB population of cells was arrested in the G1/G0 phase. Further experiments demonstrated that SBMBs decreased the expression of signal transducer and activator of transcription 3 (STAT3), Ak strain transforming (AKT), and extracellular signal-regulated kinase (Erk) and had a greater effect than SB in A2780 cells. Inhibitors of AKT, Erk and STAT3 promoted the cytotoxicity of SBMBs. Conclusion: SBMBs in combination with ultrasound may enhance the cytotoxicity efficiency of SB via the promotion of apoptosis and cell cycle arrest in ovarian cancer cells and the inactivation of the STAT3, AKT and Erk signalling pathways.

Download Full-text

Purified Vitexin Compound 1 Serves as a Promising Antineoplastic Agent in Ovarian Cancer

Frontiers in Oncology ◽

10.3389/fonc.2021.734708 ◽

2021 ◽

Vol 11 ◽

Author(s):

Kewen Ma ◽

Kuansong Wang ◽

Yingjun Zhou ◽

Nian Liu ◽

Wei Guo ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Antineoplastic Agent ◽

Chinese Herb ◽

Ovarian Cancer Cells ◽

Therapeutic Effects ◽

Dependent Manner ◽

M Phase

Ovarian cancer is a common gynecologic aggressive neoplasm. The mortality of ovarian cancer is top among gynecologic malignancies due to the insidious onset, atypical early symptoms, and chemoresistance. Therefore, it is urgent to seek another promising treatment for ovarian cancer. Purified vitexin compound 1 (VB1) is a kind of neolignan from the seed of traditional Chinese herb vitex negundo that possessed diverse pharmacological effects. VB1 can exhibit anti-neoplastic activities against various cancers. However, the role of VB1 in ovarian cancer treatment has not been elaborated, and the mechanism is unknown. The aim of this study was to investigate the therapeutic effects of VB1 in ovarian cancer cells both in vitro and in vivo, along with the molecular mechanism of action. In vitro, VB-1 can effectively suppress the proliferation, induce apoptosis, and block cell cycle at G2/M phase with a concentration dependent manner in ovarian cancer cells. Western blot assay showed that VB1 induce apoptosis via upregulating expression of cleaved-caspase3 and block cell cycle at G2/M phase through upregulating expression of P21. Meanwhile, VB1 can effectively inhibit tumor growth in xenograft mouse model. Our research indicated that VB1 can significantly exert its anti-neoplastic effects and may represent a new class of agents in ovarian cancer therapy.

Download Full-text

Cytotoxic effects of disulfiram and synergism with cisplatin on ovarian cancer cells in vitro

10.1055/s-0038-1671352 ◽

2018 ◽

Author(s):

F Guo ◽

Z Yang ◽

J Xu ◽

J Sehouli ◽

AE Albers ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Cytotoxic Effects

Download Full-text

Propofol suppresses cell viability, cell cycle progression and motility and induces cell apoptosis of ovarian cancer cells through suppressing MEK/ERK signaling via targeting circVPS13C/miR-145 axis

Journal of Ovarian Research ◽

10.1186/s13048-021-00775-3 ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Huan Lu ◽

Guanlin Zheng ◽

Xiang Gao ◽

Chanjuan Chen ◽

Min Zhou ◽

...

Keyword(s):

Cell Cycle ◽

Ovarian Cancer ◽

Cancer Cells ◽

Rna Binding ◽

Erk Signaling ◽

Luciferase Reporter ◽

Migration And Invasion ◽

Ovarian Cancer Cells ◽

Dependent Manner ◽

Vacuolar Protein

Abstract Background Propofol is a kind of common intravenous anaesthetic agent that plays an anti-tumor role in a variety of cancers, including ovarian cancer. However, the working mechanism of Propofol in ovarian cancer needs further exploration. Methods The viability and metastasis of ovarian cancer cells were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and transwell assays. Flow cytometry was used to evaluate the cell cycle and apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to examine the abundance of circular RNA vacuolar protein sorting 13 homolog C (circVPS13C) and microRNA-145 (miR-145). The target relationship between miR-145 and circVPS13C was predicted by circinteractome database and verified by dual-luciferase reporter assay, RNA-binding protein immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot assay was used to detect the levels of phosphorylated extracellular regulated MAP kinase (p-ERK), ERK, p-MAP kinse-ERK kinase (p-MEK) and MEK, in ovarian cancer cells. Results Propofol treatment suppressed the viability, cell cycle and motility and elevated the apoptosis rate of ovarian cancer cells. Propofol up-regulated miR-145 in a dose-dependent manner. Propofol exerted an anti-tumor role partly through up-regulating miR-145. MiR-145 was a direct target of circVPS13C. Propofol suppressed the progression of ovarian cancer through up-regulating miR-145 via suppressing circVPS13C. Propofol functioned through circVPS13C/miR-145/MEK/ERK signaling in ovarian cancer cells. Conclusion Propofol suppressed the proliferation, cell cycle, migration and invasion and induced the apoptosis of ovarian cancer cells through circVPS13C/miR-145/MEK/ERK signaling in vitro.

Download Full-text

Electrochemotherapy with Calcium Chloride and 17β-Estradiol Modulated Viability and Apoptosis Pathway in Human Ovarian Cancer

Pharmaceutics ◽

10.3390/pharmaceutics13010019 ◽

2020 ◽

Vol 13 (1) ◽

pp. 19

Author(s):

Zofia Łapińska ◽

Michał Dębiński ◽

Anna Szewczyk ◽

Anna Choromańska ◽

Julita Kulbacka ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Calcium Chloride ◽

Morphological Changes ◽

Cell Membrane Permeability ◽

Immunocytochemical Staining ◽

Ovarian Cancer Cells ◽

Apoptosis Pathway ◽

17Β Estradiol

Estrogens (Es) play a significant role in the carcinogenesis and progression of ovarian malignancies. Depending on the concentration, Es may have a protective or toxic effect on cells. Moreover, they can directly or indirectly affect the activity of membrane ion channels. In the presented study, we investigated in vitro the effectiveness of the ovarian cancer cells (MDAH-2774) pre-incubation with 17β-estradiol (E2; 10 µM) in the conventional chemotherapy (CT) and electrochemotherapy (ECT) with cisplatin or calcium chloride. We used three different protocols of electroporation including microseconds (µsEP) and nanoseconds (nsEP) range. The cytotoxic effect of the applied treatment was examined by the MTT assay. We used fluorescent staining and holotomographic imaging to observe morphological changes. The immunocytochemical staining evaluated the expression of the caspase-12. The electroporation process’s effectiveness was analyzed by a flow cytometer using the Yo-Pro™-1 dye absorption assay. We found that pre-incubation of ovarian cancer cells with 17β-estradiol may effectively enhance the chemo- and electrochemotherapy with cisplatin and calcium chloride. At the same time, estradiol reduced the effectiveness of electroporation, which may indicate that the mechanism of increasing the effectiveness of ECT by E2 is not related to the change of cell membrane permeability.

Download Full-text

Genetic Perturbation of Pyruvate Dehydrogenase Kinase 1 Modulates Growth, Angiogenesis and Metabolic Pathways in Ovarian Cancer Xenografts

Cells ◽

10.3390/cells10020325 ◽

2021 ◽

Vol 10 (2) ◽

pp. 325

Author(s):

Carolina Venturoli ◽

Ilaria Piga ◽

Matteo Curtarello ◽

Martina Verza ◽

Giovanni Esposito ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Pyruvate Dehydrogenase ◽

Metabolic Pathways ◽

Negative Impact ◽

Digital Pathology ◽

Pyruvate Dehydrogenase Kinase ◽

Ovarian Cancer Cells ◽

Pyruvate Dehydrogenase Kinase 1

Pyruvate dehydrogenase kinase 1 (PDK1) blockade triggers are well characterized in vitro metabolic alterations in cancer cells, including reduced glycolysis and increased glucose oxidation. Here, by gene expression profiling and digital pathology-mediated quantification of in situ markers in tumors, we investigated effects of PDK1 silencing on growth, angiogenesis and metabolic features of tumor xenografts formed by highly glycolytic OC316 and OVCAR3 ovarian cancer cells. Notably, at variance with the moderate antiproliferative effects observed in vitro, we found a dramatic negative impact of PDK1 silencing on tumor growth. These findings were associated with reduced angiogenesis and increased necrosis in the OC316 and OVCAR3 tumor models, respectively. Analysis of viable tumor areas uncovered increased proliferation as well as increased apoptosis in PDK1-silenced OVCAR3 tumors. Moreover, RNA profiling disclosed increased glucose catabolic pathways—comprising both oxidative phosphorylation and glycolysis—in PDK1-silenced OVCAR3 tumors, in line with the high mitotic activity detected in the viable rim of these tumors. Altogether, our findings add new evidence in support of a link between tumor metabolism and angiogenesis and remark on the importance of investigating net effects of modulations of metabolic pathways in the context of the tumor microenvironment.

Download Full-text

Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies

Scientific Reports ◽

10.1038/s41598-021-82686-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Marina Stasenko ◽

Evan Smith ◽

Oladapo Yeku ◽

Kay J. Park ◽

Ian Laster ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Therapeutics ◽

Ca 125 ◽

Ovarian Cancer Cells ◽

Carbohydrate Binding ◽

Matrigel Invasion ◽

Galectin 3

AbstractThe lectin, galectin-3 (Gal3), has been implicated in a variety of inflammatory and oncogenic processes, including tumor growth, invasion, and metastasis. The interactions of Gal3 and MUC16 represent a potential targetable pathway for the treatment of MUC16-expressing malignancies. We found that the silencing of Gal3 in MUC16-expressing breast and ovarian cancer cells in vitro inhibited tumor cell invasion and led to attenuated tumor growth in murine models. We therefore developed an inhibitory murine monoclonal anti–Gal3 carbohydrate-binding domain antibody, 14D11, which bound human and mouse Gal3 but did not bind human Galectins-1, -7, -8 or -9. Competition studies and a docking model suggest that the 14D11 antibody competes with lactose for the carbohydrate binding pocket of Gal3. In MUC16-expressing cancer cells, 14D11 treatment blocked AKT and ERK1/2 phosphorylation, and led to inhibition of cancer cell Matrigel invasion. Finally, in experimental animal tumor models, 14D11 treatment led to prolongation of overall survival in animals bearing flank tumors, and retarded lung specific metastatic growth by MUC16 expressing breast cancer cells. Our results provide evidence that antibody based Gal3 blockade may be a viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics.

Download Full-text

Plasma cells shape the mesenchymal identity of ovarian cancers through transfer of exosome-derived microRNAs

Science Advances ◽

10.1126/sciadv.abb0737 ◽

2021 ◽

Vol 7 (9) ◽

pp. eabb0737

Author(s):

Zhengnan Yang ◽

Wei Wang ◽

Linjie Zhao ◽

Xin Wang ◽

Ryan C. Gimple ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Plasma Cell ◽

Plasma Cells ◽

Ovarian Cancer Cells ◽

Mesenchymal Phenotype ◽

Ovarian Cancers ◽

Novel Approach

Ovarian cancer represents a highly lethal disease that poses a substantial burden for females, with four main molecular subtypes carrying distinct clinical outcomes. Here, we demonstrated that plasma cells, a subset of antibody-producing B cells, were enriched in the mesenchymal subtype of high-grade serous ovarian cancers (HGSCs). Plasma cell abundance correlated with the density of mesenchymal cells in clinical specimens of HGSCs. Coculture of nonmesenchymal ovarian cancer cells and plasma cells induced a mesenchymal phenotype of tumor cells in vitro and in vivo. Phenotypic switch was mediated by the transfer of plasma cell–derived exosomes containing miR-330-3p into nonmesenchymal ovarian cancer cells. Exosome-derived miR-330-3p increased expression of junctional adhesion molecule B in a noncanonical fashion. Depletion of plasma cells by bortezomib reversed the mesenchymal characteristics of ovarian cancer and inhibited in vivo tumor growth. Collectively, our work suggests targeting plasma cells may be a novel approach for ovarian cancer therapy.

Download Full-text

Splicing factor USP39 promotes ovarian cancer malignancy through maintaining efficient splicing of oncogenic HMGA2

Cell Death and Disease ◽

10.1038/s41419-021-03581-3 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Shourong Wang ◽

Zixiang Wang ◽

Jieyin Li ◽

Junchao Qin ◽

Jianping Song ◽

...

Keyword(s):

Ovarian Cancer ◽

Cancer Cells ◽

Malignant Tumors ◽

Splicing Factor ◽

Ovarian Cancer Cells ◽

Nuclear Speckles ◽

Aberrant Expression ◽

Intergenic Regions

AbstractAberrant expression of splicing factors was found to promote tumorigenesis and the development of human malignant tumors. Nevertheless, the underlying mechanisms and functional relevance remain elusive. We here show that USP39, a component of the spliceosome, is frequently overexpressed in high-grade serous ovarian carcinoma (HGSOC) and that an elevated level of USP39 is associated with a poor prognosis. USP39 promotes proliferation/invasion in vitro and tumor growth in vivo. Importantly, USP39 was transcriptionally activated by the oncogene protein c-MYC in ovarian cancer cells. We further demonstrated that USP39 colocalizes with spliceosome components in nuclear speckles. Transcriptomic analysis revealed that USP39 deletion led to globally impaired splicing that is characterized by skipped exons and overrepresentation of introns and intergenic regions. Furthermore, RNA immunoprecipitation sequencing showed that USP39 preferentially binds to exon-intron regions near 5′ and 3′ splicing sites. In particular, USP39 facilitates efficient splicing of HMGA2 and thereby increases the malignancy of ovarian cancer cells. Taken together, our results indicate that USP39 functions as an oncogenic splicing factor in ovarian cancer and represents a potential target for ovarian cancer therapy.

Download Full-text