scholarly journals Anti-metastatic effect of curcumin analog pentagamaboronon-0-fructose (PGB-0-F) against 4T1 breast cancer cells

2018 ◽  
Vol 23 (2) ◽  
pp. 109
Author(s):  
Yogi Ertanto ◽  
Rohmad Yudi Utomo ◽  
Riris Istighfari Jenie ◽  
Ratna Asmah Susidarti ◽  
Edy Meiyanto

Development of a chemotherapeutic agent and boron carrying pharmaceutical based on triple-negative breast cancer is important due to its metastatic progression. Metastases are often more dangerous than the primary tumor and they are responsible for 90% of all cancer deaths. The purpose of this study was to explore the anti-metastatic activities of the PGB-0 complex with fructose (PGB-0-F) against 4T1 breast cancer cells. A scratch wound healing assay was carried out to determine the migration inhibition ability of PGB-0-F, while MMP-9 expression was analysed using gelatin zymography. The testing of anti-migration activity showed that PGB-0-F inhibited in 4T1 cells, whereas the gelatin zymography assay revealed a suppression of MMP-9 expression. PGB-0-F inhibited closure on 4T1 metastatic breast cancer cells line compared with the control. PGB-0-F decreased the MMP-9 expression level compared with the control. Based on these results, PGB-0-F has the potential to be developed as a chemotherapeutic agent, and especially as an anti-metastatic agent.

Author(s):  
Dhania Novitasari ◽  
Sri Handayani ◽  
Riris Istighfari Jenie

Many natural products have been widely explored for their pharmacological activities, including anticancer activity. Hedyotis corymbosa L. is known for its anticancer properties toward several cancer cell lines. The study aims to investigate whether ethanolic extract of Hedyotis corymbosa L. (EEH) performs anticancer properties by inhibiting migration and metastasis on breast cancer cells. Cytotoxic evaluation by using MTT assay was carried out to determine EEH effect on 4T1 breast cancer cells, meanwhile to investigate the treatment of EEH in migration and metastasis inhibitory effect, scratch wound healing assay and gelatin zymography were conducted in this study. The data showed that EEH possessed cytotoxic activity with IC50 value of 400 μg/mL.  Interestingly, migration inhibitory effect was shown up to 42 hours and the activity of MMP-9 was also decreased after the treatment with EEH. According to these findings, we suggest that Hedyotis corymbosa L. promotes another anticancer properties by inhibiting migration and metastasis towards breast cancer cells.Keywords : Hedyotis corymbosa L., cytotoxicity, migration, metastatic, 4T1 breast cancer cells


2019 ◽  
Vol 20 (22) ◽  
pp. 5581
Author(s):  
Chung-Yih Wang ◽  
Chun-Yuan Chang ◽  
Chun-Yu Wang ◽  
Kaili Liu ◽  
Chia-Yun Kang ◽  
...  

Radiation is a widely used therapeutic method for treating breast cancer. N-dihydrogalactochitosan (GC), a biocompatible immunostimulant, is known to enhance the effects of various treatment modalities in different tumor types. However, whether GC can enhance the radiosensitivity of cancer cells remains to be explored. In this study, triple-negative murine 4T1 breast cancer cells transduced with multi-reporter genes were implanted in immunocompetent Balb/C mice to track, dissect, and identify liver-metastatic 4T1 cells. These cells expressed cancer stem cell (CSC) -related characteristics, including the ability to form spheroids, the expression of the CD44 marker, and the increase of protein stability. We then ex vivo investigated the potential effect of GC on the radiosensitivity of the liver-metastatic 4T1 breast cancer cells and compared the results to those of parental 4T1 cells subjected to the same treatment. The cells were irradiated with increased doses of X-rays with or without GC treatment. Colony formation assays were then performed to determine the survival fractions and radiosensitivity of these cells. We found that GC preferably increased the radiosensitivity of liver-metastatic 4T1 breast cancer cells rather than that of the parental cells. Additionally, the single-cell DNA electrophoresis assay (SCDEA) and γ-H2AX foci assay were performed to assess the level of double-stranded DNA breaks (DSBs). Compared to the parental cells, DNA damage was significantly increased in liver-metastatic 4T1 cells after they were treated with GC plus radiation. Further studies on apoptosis showed that this combination treatment increased the sub-G1 population of cells, but not caspase-3 cleavage, in liver-metastatic breast cancer cells. Taken together, the current data suggest that the synergistic effects of GC and irradiation might be used to enhance the efficacy of radiotherapy in treating metastatic tumors.


Oncogene ◽  
2019 ◽  
Vol 39 (7) ◽  
pp. 1543-1556 ◽  
Author(s):  
Ran Cheng ◽  
Sandrine Billet ◽  
Chuanxia Liu ◽  
Subhash Haldar ◽  
Diptiman Choudhury ◽  
...  

Abstract Periodontal diseases can lead to chronic inflammation affecting the integrity of the tooth supporting tissues. Recently, a striking association has been made between periodontal diseases and primary cancers in the absence of a mechanistic understanding. Here we address the effect of periodontal inflammation (PI) on tumor progression, metastasis, and possible underlining mechanisms. We show that an experimental model of PI in mice can promote lymph node (LN) micrometastasis, as well as head and neck metastasis of 4T1 breast cancer cells, both in early and late stages of cancer progression. The cervical LNs had a greater tumor burden and infiltration of MDSC and M2 macrophages compared with LNs at other sites. Pyroptosis and the resultant IL-1β production were detected in patients with PI, mirrored in mouse models. Anakinra, IL-1 receptor antagonist, limited metastasis, and MDSC recruitment at early stages of tumor progression, but failed to reverse established metastatic tumors. PI and the resulting production of IL-1β was found to promote CCL5, CXCL12, CCL2, and CXCL5 expression. These chemokines recruit MDSC and macrophages, finally enabling the generation of a premetastatic niche in the inflammatory site. These findings support the idea that periodontal inflammation promotes metastasis of breast cancer by recruiting MDSC in part by pyroptosis-induced IL-1β generation and downstream CCL2, CCL5, and CXCL5 signaling in the early steps of metastasis. These studies define the role for IL-1β in the metastatic progression of breast cancer and highlight the need to control PI, a pervasive inflammatory condition in older patients.


Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1567
Author(s):  
Gamze Tanriover ◽  
Sayra Dilmac ◽  
Nuray Erin

Breast cancer treatments continue to be investigated with supported by new treatment methods. Melatonin is a hormone that can be effective in the treatment of breast cancer due to its anti-oxidant effect. Melatonin had previously shown to inhibit proliferation of cancer cells. In this study, we aimed to determine the effect of melatonin on the proliferation of metastatic breast cancer cells in comparison to doxorubicin, a well-known chemotherapeutic agent. Doxorubicin inhibited proliferation of metastatic breast cancer cells while melatonin has no effect. We are currently examining the effects of melatonin and doxorubicin combination therapy on metastatic breast cancer cells.


Author(s):  
Lodyta Nawang Tika ◽  
Layung Sekar Sih Wikanthi ◽  
Shofa Annur ◽  
Retno Murwanti

Metastasis is the main cause of death among brast cancer patient. Pleorotus ostreatus is known as anticancer agent that inhibits angiogenesis. Ethanolic extract of Pleorotus ostreatus (EEP) which contains lovastatin is predicted to inhibit metastatic cancer through inhibition of MMP-2 and MMP-9. The aim of this study was to determined antiproliferative and anti metastatic activity of EEPw (Ethanolic extract of wet Pleorotus ostreatus) and EEPd (Ethanolic extract of dried Pleorotus ostreatus ) in 4T1 metastatic breast cancer cells line. Qualitative analysis of lovastatin was determined by thin layer chromatography (TLC) using dicloromethan and etil acetat as mobile phase and lovastatin standard. Scratch wound healing assay was used to determine migration inhition ability of EEP while MMP-9 and MMP-2 activity were analysed by gelatine zymography. Molecular docking was performed to know the interaction between lovastatin and MMP-2 & MMP-9. The result showed that EEPw and EEPd contain lovastatin which were proved by spray reaction with anisaldehid. Each of EEPw and EPPd had cytotoxic activity with IC50 760 and 400 μg/mL respectively. Both of them inhibited closure for about 50 % on 4T1 metastatic breast cancer cells line compared to control. Either EEPw or EEPd decreased MMP-9 expression level compared to control. Lovastatin had higher affinity to bond with either MMP-2 or MMP-9 than native ligand. Overall, EEP could be developed as anticancer agent which was targeted on MMP-2 and MMP-9.Keywords : Pleurotus ostreatus, 4T1 metastatic cells, MMP-2, MMP-2, antimetastatic


2021 ◽  
Author(s):  
Joji Nakayama ◽  
Takamasa Ishikawa ◽  
Tatsunori Nishimura ◽  
Sanae Yamanaka ◽  
Noriko Gotoh ◽  
...  

AbstractAbnormal biosyntheses of steroid hormones and dysregulation of steroid hormone receptors contribute to breast cancer metastasis but the mechanisms of that are poorly understand. Here we report a stress hormone producing enzyme, Hydroxysteroid (11-Beta) Dehydrogenase 1 (HSD11β1) promotes breast cancer metastasis. HSD11β1 was ectopically expressed in seventy-one percent of triple-negative breast tumors and correlated with shorter overall survival. HSD11β1 significantly promoted breast cancer metastasis through induction of epithelial-to-mesenchymal transition (EMT); conversely, pharmacologic and genetic inhibition of HSD11β1 suppressed metastatic progression of breast cancer cells. Moreover, 11-hydroxyprogesterone (11-OHP) whom HSD11β1 produced in breast cancer cells, conferred metastatic properties on non-metastatic breast cancer cells through induction of EMT. We identified Peroxisome Proliferator-activated Receptor Alpha (PPAR-α) as essential for both HSD11β1 and 11OHP-driven EMT. Knockdown of PPAR-α induced MET on HSD11β1-expressing breast cancer cells. Taken together, HSD11β1 promotes breast cancer metastasis and would be a novel target for suppressing breast cancer metastasis.


Author(s):  
Lailatul Qodria ◽  
Indah Hairunisa ◽  
Rohmad Yudi Utomo ◽  
Adam Hermawan ◽  
Edy Meiyanto

Breast cancer with Human Epidermal Growth Factor Receptor (HER)2 overexpression increases tumor progession and lead to metastasis, which is primarily cause of mortality in breast cancer. Pentagamaboronon-0 Sorbitol (PGB-0-So) is an aquoeous formulation of curcumin analog, PGB-0, with sorbitol. This compound has been developed as an anti-cancer chemotherapeutic agent and a boron carrying pharmaceutical for boron neutron capture therapy (BNCT). The aims of this study are to investigate antimetastatic activities of PGB-0-So against HER2-overexpressed MCF-7 breast cancer (MCF-7/HER2) cells. The MTT cytotoxicity assay of PGB-0-So exhibited cytotoxic effect with an IC50 value of 35 μM. The testing of anti-migration activity using the scratch wound healing assay demonstrated that PGB-0-So inhibited the closure of the wound on MCF-7/HER2 cells compare to the control. Furthermore, PGB-0-So was able to suppress matrix metalloproteinase (MMP)-9 activities, based on the gelatin zymography assay. In conclusion, PGB-0-So has potency to be developed as an anti-cancer agent against metastatic breast cancer.Keywords : PGB-0-So, anti-metastatsis, cell migration, MMP-9, MCF-7/HER2


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