Light activation of cyclometalated ruthenium complexes drives towards caspase 3 dependent apoptosis in gastric cancer cells

2020 ◽  
Vol 208 ◽  
pp. 111080 ◽  
Author(s):  
Jorge Andrés Solís-Ruiz ◽  
Anaïs Barthe ◽  
Gilles Riegel ◽  
Rafael Omar Saavedra-Díaz ◽  
Christian Gaiddon ◽  
...  
2001 ◽  
Vol 93 (6) ◽  
pp. 916-916 ◽  
Author(s):  
XH Jiang ◽  
BCY Wong ◽  
ST Yuen ◽  
SH Jiang ◽  
CH Cho ◽  
...  

2020 ◽  
Vol 19 (4) ◽  
pp. 514-519
Author(s):  
Ming-Jen Sheu ◽  
Jen-Ning Tsai ◽  
Wai-Lun Tam ◽  
Jer-Yuh Liu ◽  
Li-Sung Hsu

Given the increasing incidence of gastric cancer and its high rate of metastasis, drug resistance and the mortality rate remain high. Ocimum gratissimum, a botanical species of Ocimum known to exhibit general anti-inflammatory, antioxidant, and anticancer activities has not yet been evaluated for gastric cancer proliferation. In this study, we have demonstrated that O. gratissimum extract significantly reduces the viability of gastric cancer cells by triggering apoptosis, elevating levels of ROS, and enhanced cleavage of poly-ADP-ribose polymerase and caspase-3. Western blot analysis indicated that O. gratissimum extract enhanced the cleavage of PARP and caspase-3. Moreover, O. gratissimum extract inhibited extracellular signal-regulated kinase 1/2 and increased activities of p38, a stress stimulated kinase. In conclusion, our findings show that O. gratissimum extract may be a potential antigastric cancer agent.


2020 ◽  
Author(s):  
Jinyan Zhao ◽  
Weilan Lan ◽  
Jun Peng ◽  
Bin Guan ◽  
Jie Liu ◽  
...  

Abstract Background: Multidrug resistance (MDR) is a critical reason of cancer chemotherapy failure. Babao dan (BBD) is a classical and famous traditional Chinese patent medicine, which has been reported to has anti-gastric cancer activity. However, the roles and molecular mechanisms of the reversal of MDR of gastric cancer by BBD have not been well described until now. Methods: SGC-7901 and SGC-7901/DDP cells were used in this study, and drug resistance and evaluation of the reversal effect of BBD was determined using MTT assays in SGC7901/DDP cells. Doxorubicin (DOX) and Rhodamin123 (Rho123) staining was performed to assess BBD effects on drug accumulation and efflux of drug-resistant gastric cancer cells. Cell apoptosis was directly assessed using DAPI staining. Apoptotic and dead cells were detected by flow cytometry after staining with Annexin V-FITC and propidium iodide (PI). Cyto-ID assays were performed to examine cellular autophagy. Changes in cell protein expression of ABCB1, ABCC1, ABCG2, Bax, Bcl-2, caspase-3, cleaved-caspase-3, LC3, p62, Beclin1 and the PI3K/AKT/mTOR pathway were detected by Western blot. Inhibition of autophagy with 3-MA, chloroquine (CQ) and PI3K antagonist (LY294002) or agonist (740Y-P) , uncovered a role for the potentially downregulated signaling pathway, PI3K/AKT/mTOR.Results: The SGC7901/DDP cell line exhibited multi-drug resistance to DDP, DOX and 5-fluorouracil (5-FU) and the drug resistant index (RI) of DDP, DOX and 5-FU were 1.86, 1.50 and 47.70, respectively. BBD reversed the MDR of SGC7901/DDP cells by increasingDOX accumulation, reducing Rh123 efflux and down-regulating the expression of ABCB1, ABCC1, ABCG2. Furthermore, BBD induced apoptosis in SGC7901/DDP cells through regulating caspase-3, cleaved-caspase-3, Bax and Bcl-2. Moreover, BBD induced autophagy in DDP-resistant gastric cancer cells via regulating p62, LC3 and Beclin1. Pathway analyses suggested BBD may inhibit PI3K/AKT/mTOR pathway activity and subsequent autophagy induction. Conclusions: BBD may reverse the MDR of gastric cancer cells, and promote autophagic death via inactivation of the PI3K/AKT/mTOR signaling pathway.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 968
Author(s):  
Katarzyna Supruniuk ◽  
Robert Czarnomysy ◽  
Anna Muszyńska ◽  
Iwona Radziejewska

MUC1 mucin is a transmembrane glycoprotein aberrantly overexpressed and underglycosylated in most epithelium origin cancers. Combining chemotherapeutics with monoclonal antibodies toward cancer-related antigens is one of the new strategies in cancer therapies. In this study, we assessed the effectiveness of 10 μM cisplatin (cisPt), two pyrazole-platinum(II) complexes (PtPz4 and PtPz6), and 5 μg/mL anti-MUC1 used as monotherapy, as well as cisplatin and its derivatives combined with mAb on apoptotic response and specific cancer-related sugar antigens in AGS gastric cancer cells. Flow cytometry, RT-PCR, Western blotting, and ELISA tests were applied to determine the influence of examined compounds on analyzed factors. PtPz6 combined with anti-MUC1 revealed the strongest apoptotic response compared to control and monotherapy. The combined action of both cisPt derivatives and anti-MUC1 was more effective than monotherapy in relation to Bad, Bcl-xL, Bcl-2, caspase-9, caspase-3, as well as pro- and cleaved caspase-3 protein, and T, sialyl Tn sugar antigens in cell lysates, and Tn, T, sialyl Tn, sialyl T antigens in culture medium. Additionally, PtPz4 administrated with mAb was revealed to be more potent than used alone with regard to Bax protein and Bid expression, and PtPz6 used in complex with anti-MUC1 revealed more efficient action towards Akt and sialyl T antigen expression. These data indicate the rationality of the potential application of combined treatment of anti-MUC1 and cisPt derivatives in gastric cancer therapy.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21020-21020
Author(s):  
K. Yeh ◽  
Y. Shen ◽  
Y. Chiang ◽  
P. Liu ◽  
C. Huang ◽  
...  

21020 Background: Exploration of molecular determinants for chemosensitivity is the key element of personalized cancer therapy. Cyclin E is a major G1-phase cyclin, together with the CDK2, which mediates phosphorylation and functional inactivation of Rb protein. Cyclin E overexpression has been demonstrated in a variety of cancers, including human gastric cancers (GC), while its biologic significance in drug therapy remains unclear. Previously, we have demonstrated that cyclin D1 overexpression plays an important role in differential chemosensitivity of human GC cells (Proc Am Assoc Cancer Res 2004; 45: abstract 4888). In this study, we examine the roles between cyclin E overexpression and chemosensitivity of human GC cells. Methods: Compared human gastric cancer cells (NCI-N87) with stably transfected cells (N87-CyE), which have 2-fold overexpression of cyclin E, the IC50 for gemcitabine (2'-2'-difluoro- deoxycytidine, dFdC) was more than 1-log lower in N87-CyE (17.0 ± 2.7 nM) than N87 cells (113.7 ± 6.5 nM) by MTT colorimetric cytotoxicity assay. In contrast, the N87-CyE cells are only slightly more chemosensitive to taxanes (paclitaxel and docetaxel), and confer largely identical chemosensitivity to 5-FU, cisplatin, and irinotecan (CPT-11). We applied RNA interference (RNAi) of cyclin E to N87 cells. The stably transfected N87-CyE/RNAi cells readily confer gemcitabine resistance with the IC50 for gemcitabine of 124.5 ± 1.6 nM. Results: Gemcitabine-induced apoptosis in N87, N87-CyE, or N87-CyE/RNAi cells was shown in either caspase-3 or PARP (poly ADP-ribose polymerase) cleavage assay by Western blotting, and Annexin-V-FITC apoptosis detection by flowcytometry. The threshold concentration of gemcitabine for caspase-3 and PARP cleavage was 10–25 nM for N87-CyE, and 100–200 nM for N87 or N87-CyE/RNAi, respectively. Conclusions: Our data demonstrate that preferential chemosensitivity to gemcitabine by cyclin E overexpression in gastric cancer cells. Gemcitabine-induced apoptosis is enhanced by cyclin E overexpression, while is reduced by RNAi of cyclin E. Further studies for potential clinical use of gemcitabine in personalized chemotherapy for cyclin E or cyclin D1-overexpressing GC are warranted (supported by the grants of NHRI-CN-CA9201S, Taiwan). No significant financial relationships to disclose.


Oncotarget ◽  
2016 ◽  
Vol 7 (16) ◽  
pp. 22623-22631 ◽  
Author(s):  
Min Shi ◽  
Xiao-Jie Lu ◽  
Juan Zhang ◽  
Hua Diao ◽  
Guangming Li ◽  
...  

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