scholarly journals Cajanol Sensitizes A2780/Taxol Cells to Paclitaxel by Inhibiting the PI3K/Akt/NF-κB Signaling Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Ming Sui ◽  
Hairong Yang ◽  
Mingqi Guo ◽  
Wenle Li ◽  
Zheng Gong ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Pigeon Pea ◽  
Multi Drug Resistance ◽  
Paclitaxel Resistance ◽  
Gynecological Malignancy ◽  
Staining Methods

Ovarian cancer is the second most common gynecological malignancy, and one of the most deadly. The bottleneck restricting the treatment of ovarian cancer is its multi-drug resistance to chemotherapy. Cajanol is an isoflavone from pigeon pea (Cajanus cajan) that has been reported to have anti-tumor activity. In this work, we evaluate the effect of cajanol in reversing paclitaxel resistance of the A2780/Taxol ovarian cancer cell line in vitro and in vivo, and we discuss its mechanism of action. We found that 8 μM cajanol significantly restored the sensitivity of A2780/Taxol cells to paclitaxel, and in vivo experiments demonstrated that the combination of 0.5 mM/kg paclitaxel and 2 mM/kg cajanol significantly inhibited the growth of A2780/Taxol metastatic tumors in mice. Flow cytometry, fluorescence quantitative PCR, western blotting and immunohistochemical staining methods were used to study the mechanism of reversing paclitaxel resistance with cajanol. First, we determined that cajanol inhibits paclitaxel efflux in A2780/Taxol cells by down-regulating permeability glycoprotein (P-gp) expression, and further found that cajanol can inhibit P-gp transcription and translation through the PI3K/Akt/NF-κB pathway. The results of this work are expected to provide a new candidate compound for the development of paclitaxel sensitizers.

scholarly journals Inhibition of Phosphatidylinositol 3-Kinase Increases Efficacy of Cisplatin in in Vivo Ovarian Cancer Models

Endocrinology ◽  
2006 ◽  
Vol 147 (4) ◽  
pp. 1761-1769 ◽  
Author(s):  
Tsuyoshi Ohta ◽  
Masahide Ohmichi ◽  
Tadashi Hayasaka ◽  
Seiji Mabuchi ◽  
Maki Saitoh ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Dominant Negative ◽  
Pi3k Inhibitor ◽  
Ovarian Cancer Cells ◽  
Phosphatidylinositol 3 Kinase ◽  
Phosphatidylinositol 3

The phosphatidylinositol 3-kinase (PI3K)/Akt cascade has an important role in the resistance of ovarian cancer cells to cisplatin in vitro; however, there have been no reports about whether blocking the PI3K/Akt cascade enhances the sensitivity to cisplatin in vivo. We investigated whether inhibition of PI3K increased the efficacy of cisplatin in an in vivo ovarian cancer model. Blocking the PI3K/Akt cascade with a PI3K inhibitor (wortmannin) increased the efficacy of cisplatin-induced inhibition of intraabdominal dissemination and production of ascites in athymic nude mice inoculated ip with the Caov-3 human ovarian cancer cell line. In addition, wortmannin increased the efficacy of cisplatin-induced apoptosis in tumors cells. There were no detectable side effects in mice treated with wortmannin. Moreover, the antitumor effect of cisplatin detected in mice inoculated with Caov-3 cells stably transfected with empty vector was significantly attenuated, compared with mice inoculated with Caov-3 cells stably transfected with a dominant-negative Akt, K179M-Akt. We confirmed that wortmannin blocked Akt phosphorylation and the downstream targets of the PI3K/Akt cascade, such as BAD (Bcl-2-associated death protein) and nuclear factor-κB in vivo by immunohistochemical staining and Western blotting. In accordance with the previously reported in vitro results, these in vivo results support the idea that combination therapy with cisplatin and a PI3K inhibitor would increase the therapeutic efficacy of cisplatin.

scholarly journals Overexpressing the CCL2 chemokine in an epithelial ovarian cancer cell line results in latency of in vivo tumourigenicity

Oncogenesis ◽  
2012 ◽  
Vol 1 (9) ◽  
pp. e27-e27 ◽  
Author(s):  
P Wojnarowicz ◽  
K Gambaro ◽  
M de Ladurantaye ◽  
M C J Quinn ◽  
D Provencher ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Epithelial Ovarian Cancer Cell

scholarly journals White Spot Syndrome Virus Open Reading Frame 222 Encodes a Viral E3 Ligase and Mediates Degradation of a Host Tumor Suppressor via Ubiquitination

2006 ◽  
Vol 80 (8) ◽  
pp. 3884-3892 ◽  
Author(s):  
Fang He ◽  
Beau J. Fenner ◽  
Andrew K. Godwin ◽  
Jimmy Kwang
Keyword(s):  
Tumor Suppressor ◽  
Cell Line ◽  
White Spot Syndrome Virus ◽  
Ovarian Cancer Cell Line ◽  
E3 Ligase ◽  
Cancer Cell Line ◽  
White Spot ◽  
White Spot Syndrome

ABSTRACT We have characterized a white spot syndrome virus (WSSV) RING-H2-type protein, WSSV222, which is involved in ubiquitination. WSSV222 exhibits RING-H2-dependent E3 ligase activity in vitro in the presence of the specific conjugating enzyme UbcH6. Mutations in the RING-H2 domain abolished WSSV222-dependent ubiquitination, revealing the importance of this domain in WSSV222 function. Yeast two-hybrid and pull-down analyses revealed that WSSV222 interacts with a shrimp tumor suppressor-like protein (TSL) sharing 60% identity with human OVCA1. To better characterize the interaction of WSSV222 and TSL in vivo, we established a stable TSL-expressing cell line derived from the human ovarian cancer cell line A2780, where we observed a TSL-dependent prolonged G1 phase. Furthermore, we detected WSSV222-mediated ubiquitination and MG132-sensitive degradation of TSL both in shrimp primary cell culture and in the TSL-expressing cell line. Transient expression of TSL in BHK cells leads to apoptosis, which was rescued by WSSV222. Taken together, our data suggest that WSSV222 acts as an antiapoptosis protein by ubiquitin-mediated proteolysis of TSL to ensure successful WSSV replication in shrimp.

scholarly journals Cytotoxicity of Standardized Curcuminoids Mixture against Epithelial Ovarian Cancer Cell Line SKOV-3

2020 ◽  
Vol 88 (1) ◽  
pp. 11 ◽  
Author(s):  
Heba Almosa ◽  
Mihal Alqriqri ◽  
Iuliana Denetiu ◽  
Mohammed A. Baghdadi ◽  
Mohammed Alkhaled ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Line ◽  
Cancer Cell ◽  
Ovarian Cancer Cell ◽  
Ovarian Cancer Cell Line ◽  
Cancer Cell Line ◽  
Reversed Phase ◽  
Potential Contribution ◽  
Dependent Manner

Herbal medicine has been in use for centuries for a wide variety of ailments; however, the efficacy of its therapeutic agents in modern medicine is currently being studied. Curcuminoids are an example of natural agents, widely used due to their potential contribution in the prevention and treatment of cancer. In this study, the three main compounds of curcuminoids—curcumin, desmethoxycurcumin, and bisdesmethoxycurcumin—were determined by reversed-phase high performance liquid chromatography (HPLC) to quantify total content in a mixture. Subsequently, the effect of the three curcuminoids, employed as one sample, was evaluated, to study the proliferation, apoptosis, cell cycle, and migration of the human ovarian cancer cell line SKOV-3. The results reveal that curcuminoids inhibit the proliferation of SKOV-3 cells with concentration- and time-dependent mechanisms. The morphological analysis of the treated SKOV-3 cells showed a typical apoptotic phenotype—cell shrinkage and membrane blebbing in a dose-dependent manner. In addition, flow cytometry demonstrated an increase in apoptosis with an IC50 of 30 µM curcuminoids. The migration of SKOV-3 cells was also inhibited, reflected by a decrease in wound area. Furthermore, the curcuminoids were found to have no stimulation effect on the expression of cytokines TNF-α and IL-10. These results suggest that a curcuminoid mixture can effectively suppress epithelial cancer cell growth in vitro by inducing cellular changes and apoptosis.

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