Therapeutic Inducers of Apoptosis in Ovarian Cancer

Binju, Mudra; Amaya-Padilla, Monica Angelica; Wan, Graeme; Gunosewoyo, Hendra; Rahmanto, Yohan Suryo; Yu, Yu

doi:10.3390/cancers11111786

Cited by 54 publications

(51 citation statements)

References 203 publications

(239 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ratio of BCL-2/BAX determines the fate of cells. Overexpression of BCL2 inhibits cell apoptosis, leads to resistance to cisplatin, and results in the poor prognosis of cancer patients [43]. In the current study, the treatment of ovarian and endometrial cancer cells with DDP and progesterone-calcitriol combination significantly decreased the BCL2.…”

Section: Discussionsupporting

confidence: 50%

Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

et al. 2020

View full text Add to dashboard Cite

Initially, patients that respond to cisplatin (DDP) treatment later relapse and develop chemoresistance. Agents that enhance DDP effectiveness will have a significant impact on cancer treatment. We have shown pronounced inhibitory effects of the progesterone-calcitriol combination on endometrial and ovarian cancer cell growth. Here, we examined whether and how progesterone-calcitriol combination potentiates DDP anti-tumor effects in cancer cells. Ovarian and endometrial cancer cells treated with various concentrations of DDP showed a concentration-dependent decrease in cell proliferation. Concurrent treatment of cells with DDP and progesterone-calcitriol ombination potentiated anticancer effects of DDP compared to DDP-calcitriol, or DDP-progesterone treated groups. The anticancer effects were mediated by increased caspase-3, BAX, and decreased BCL2 and PARP-1 expression in DDP and progesterone-calcitriol combination-treated cells. Stimulation of the PI3K/AKT and MAPK/ERK pathways seen in cancer cells was reduced in DDP-progesterone-calcitriol treated cells. Pretreatment of cells with specific inhibitors further diminished AKT and ERK expression. Furthermore, progesterone-calcitriol potentiated the anti-growth effects of DDP on cancer cells by attenuating the expression of SMAD2/3, multidrug resistance protein- 1 (MDR-1), and ABC transporters (ABCG1, and ABCG2), thereby impeding the efflux of chemo drugs from cancer cells. These results suggest a potential clinical benefit of progesterone-calcitriol combination therapy when used in combination with DDP.

show abstract

Section: Discussionsupporting

confidence: 50%

Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The red lines denoted the activity restricted by UDCA. especially the expression of several members of the Bcl-2 family (Binju et al, 2019). The nuclear fraction of Nrf2 is able to bind to the Bcl-2 promoter and activate an anti-apoptotic program (Gupta et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…As(III) exposure stimulated excessive ROS generation, which seems to play a critical role in promotion the activity of p53 pathway ( Sena and Chandel, 2012 ; Alamolhodaei et al., 2015 ). p53 is a tumor suppressor protein that promotes the apoptotic process ( Jiang and Rusling, 2019 ; Silva-Adaya et al., 2020 ) and directly regulate the activity of the pro-apoptotic protein Bax, which further facilitates mitochondrial membrane permeabilization and apoptosis, especially the expression of several members of the Bcl-2 family ( Binju et al., 2019 ). The nuclear fraction of Nrf2 is able to bind to the Bcl-2 promoter and activate an anti-apoptotic program ( Gupta et al., 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Ursodeoxycholic Acid Protects Against Arsenic Induced Hepatotoxicity by the Nrf2 Signaling Pathway

Zhang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Arsenic is ubiquitous toxic metalloid responsible for many human diseases all over the world. Contrastingly, Ursodeoxycholic acid (UDCA) has been suggested as efficient antioxidant in various liver diseases. However, there are no reports of the effects of UDCA on arsenious acid [As(III)]-induced hepatotoxicity. The objective of this study is to elucidate the protective actions of UDCA on As(III)-induced hepatotoxicity and explore its controlling role in biomolecular mechanisms in vivo and in vitro. The remarkable liver damage induced by As(III) was ameliorated by treatment with UDCA, as reflected by reduced histopathological changes of liver and elevation of serum AST, ALT levels. UDCA play a critical role in stabilization of cellular membrane potential, inhibition of apoptosis and LDH leakage in LO2 cells. Meanwhile, the activities of SOD, CAT and GSH-Px and the level of TSH, GSH were enhanced with UDCA administration, while the accumulations of intracellular ROS, MDA and rate of GSSG/GSH were decreased in vivo and in vitro. Further study disclosed that UDCA significantly inhibited As(III)-induced apoptosis through increasing the expression of Bcl-2 and decreasing the expression of Bax, p53, Cyt C, Cleaved caspase-3 and 9. Moreover, UDCA promoted the expression of nuclear Nrf2, HO-1, and NQO1, although arsenic regulated nuclear translocation of Nrf2 positively. When Nrf2 was silenced, the protective effect of UDCA was abolished. Collectively, the results of this study showed that UDCA protects hepatocytes antagonize As(III)-induced cytotoxicity, and its mechanism may be related to activation of Nrf2 signaling.

show abstract

“…Of note, although Bcl-2 pro-survival proteins can prolong the survival period of tumor cells in hematological tumors, playing an important role in tumori-genesis ( 54 ), the truth seems to be opposite in ovarian cancer cell lines. Although the expression of Bcl-2 family proteins in ovarian cancer cells and tissues has not yet been fully elucidated, studies have confirmed that Bcl-2 family proteins play a key role in ovarian cancer chemotherapy ( 56 , 57 ). Bcl-2 pro-survival proteins are listed below:…”

Section: Bcl-2 Family Members In Ovarian Cancermentioning

confidence: 99%

Bcl‑2 family: Novel insight into individualized therapy for ovarian cancer (Review)

et al. 2020

View full text Add to dashboard Cite

Chemoresistance to platinum-based chemotherapy for ovarian cancer in the advanced stage remains a formidable concern clinically. Increasing evidence has revealed that apoptosis represents the terminal events of the anti-tumor mechanisms of a number of chemical drugs and has a close association with chemoresistance in ovarian cancer. The B-cell lymphoma-2 (Bcl-2) family plays a crucial role in apoptosis and has a close association with chemoresistance in ovarian cancer. Some drugs that target Bcl-2 family members have shown efficacy in overcoming the chemoresistance of ovarian cancer. A BH3 profiling assay was found to be able to predict how primed a cell is when treated with antitumor drugs. The present review summarizes the role of the Bcl-2 family in mediating cell death in response to antitumor drugs and novel drugs that target Bcl-2 family members. The application of the new functional assay, BH3 profiling, is also discussed herein. Furthermore, the present review presents the hypothesis that targeting Bcl-2 family members may prove to be helpful for the individualized therapy of ovarian cancer in clinical practice and in laboratory research.

show abstract

Therapeutic Inducers of Apoptosis in Ovarian Cancer

Cited by 54 publications

References 203 publications

Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

Progesterone-Calcitriol Combination Enhanced Cytotoxicity of Cisplatin in Ovarian and Endometrial Cancer Cells In Vitro

Ursodeoxycholic Acid Protects Against Arsenic Induced Hepatotoxicity by the Nrf2 Signaling Pathway

Bcl‑2 family: Novel insight into individualized therapy for ovarian cancer (Review)

Contact Info

Product

Resources

About