Therapeutic Effects of Matrine on Primary and Metastatic Breast Cancer

Matrine, one of the main components extracted from a traditional Chinese herb, Sophora flavescens Ait, has displayed anti-cancer activity in several types of cancer cells. This study aims to evaluate the therapeutic benefits of matrine on primary and metastatic breast cancer. Matrine inhibited the viability of and induced apoptosis in human MCF-7 and mouse 4T1 breast cancer cells in a dose-dependent manner in vitro as shown by MTT assay, flow cytometry and laser scanning confocal microscopy. Administration of matrine inhibited the growth of primary tumors and their metastases to lungs and livers, in a dose-dependent manner, in a highly metastatic model of 4T1 breast cancer established in syngeneic Balb/c mice. Tumors from matrine-treated mice had a smaller proliferation index, shown by immunostaining with an anti-Ki-67 antibody, a greater apoptosis index, shown by TUNEL-staining, and a less microvessel density, shown by immunostaining with an anti-CD31 A antibody, compared to the controls. Western blot analysis of tumoral homogenates indicated that matrine therapy reduced the ratio of Bcl-2/Bax, downregulated the expressions of VEGF and VEGFR-2, and increased the activation of caspase-3 and caspase-9. This study suggests matrine may be a potent agent, from a natural resource, for treating metastatic breast cancer because of its anti-apoptotic, anti-proliferative and anti-angiogenic activities.

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Methanolic Extract of Red Betel Leaves (Piper crocatum Ruiz & Pav) Perform Cytotoxic Effect and Antimigration Activity toward Metastatic Breast Cancer

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev8iss3pp94-100 ◽

2018 ◽

Vol 8 (3) ◽

pp. 94 ◽

Cited By ~ 1

Author(s):

Meirizky Zulharini ◽

Ika Rahmawati Sutejo ◽

Hilyatul Fadliyah ◽

Riris Istighfari Jenie

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Cytotoxic Effect ◽

Methanolic Extract ◽

Metastatic Breast ◽

Inhibitory Effect ◽

Dependent Manner ◽

4T1 Cells

Breast cancer is one type of cancer with a high mortality rate due to its metastatic property. Red betel leaves (Piper crocatum Ruiz dan Pav) has been known as herbal medicine containing biophenolic, such as apigenin and luteolin derivatives which has cytotoxic activity toward cancer cells. This study is intended to explore the inhibitory effect of Piper crocatum leaves methanolic extract (PCM) on cell proliferation and migration by using 4T1 cells as model of metastatic breast cancer. By using MTT assay, PCM performed cytotoxic activity in a dose dependent manner with IC50 value of 120 μg/mL. Wound healing assay revealed that migration inhibitory activity of PCM on 4T1 cells at the concentration of 30 µg/mL. In conclusion, PCM perform cytotoxic effect and antimigration activity toward metastatic breast cancer cells.Keywords : breast cancer cells, Piper crocatum Ruiz & Pav, cytotoxic, cell mgration

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Oyster Mushroom (Pleurotus ostreatus) Inhibits Migration and Metastasis on 4T1 Breast Cancer Cells

Indonesian Journal of Cancer Chemoprevention ◽

10.14499/indonesianjcanchemoprev7iss3pp99-103 ◽

2017 ◽

Vol 7 (3) ◽

pp. 99

Author(s):

Lodyta Nawang Tika ◽

Layung Sekar Sih Wikanthi ◽

Shofa Annur ◽

Retno Murwanti

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Cancer Cells ◽

Pleurotus Ostreatus ◽

Breast Cancer Cells ◽

Anticancer Agent ◽

Metastatic Cancer ◽

Metastatic Breast ◽

Ethanolic Extract ◽

4T1 Breast Cancer

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

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Anti-proliferative and Anti-metastatic Potential of Curcumin Analogue, Pentagamavunon-1 (PGV-1), Toward Highly Metastatic Breast Cancer Cells in Correlation with ROS Generation

Advanced Pharmaceutical Bulletin ◽

10.15171/apb.2019.053 ◽

2019 ◽

Vol 9 (3) ◽

pp. 445-452 ◽

Cited By ~ 7

Author(s):

Edy Meiyanto ◽

Herwandhani Putri ◽

Yonika Arum Larasati ◽

Rohmad Yudi Utomo ◽

Riris Istighfari Jenie ◽

...

Keyword(s):

Breast Cancer ◽

Cell Cycle ◽

Metastatic Breast Cancer ◽

Cytotoxic Activity ◽

Cancer Cells ◽

Metastatic Breast ◽

Cell Senescence ◽

Dependent Manner ◽

Curcumin Analogue ◽

4T1 Cells

Purpose: Pentagamavunon-1 (PGV-1) is a curcumin analogue that shows cytotoxic activity in various cancer cells. In this study, we evaluated the effect of PGV-1 on a highly metastatic breast cancer cell line, the 4T1 cells, as an anti-metastatic and anti-proliferative agent. Methods: Cell viability was evaluated using MTT assay; while cell cycle profile, apoptosis incidence, and ROS intracellular level were determined by flow cytometry. Cell senescence was observed under senescence-associated-β-galactosidase (SA-β-gal) staining assay. The expression of matrixmetalloproteinase-9 (MMP-9) was determined using immunoreaction based-ELISA, while other proteins expression were detected using immunoblotting. Results: Curcumin and PGV-1 showed cytotoxic effects on 4T1 cells with IC50 value of 50 and 4 µM, respectively. The cytotoxic activity of PGV-1 was correlated to the induction of G2/M cell cycle arrest and cell senescence. Furthermore, PGV-1 increased the accumulation of intracellular ROS level. We also revealed that PGV-1 bound to several ROS-metabolizing enzymes, including glyoxalase I (GLO1), peroxiredoxin 1 (PRDX1), N-ribosyldihydronicotinamide: quinone reductase 2 (NQO2), aldo-keto reductase family 1 member c1 (AKR1C1). As an antimetastatic agent, PGV-1 showed less inhibitory effect on cell migration compared to curcumin. However, PGV-1 significantly decreased MMP-9 protein expression in a dose-dependent manner suggesting it still potent to inhibit metastatic cells. Conclusion: Overall, our findings suggest that PGV-1 is potential to be developed as an antiproliferative and anti-metastatic agent.

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