scholarly journals Chrysosplenol d, a Flavonol from Artemisia annua, Induces ERK1/2-Mediated Apoptosis in Triple Negative Human Breast Cancer Cells

2020 ◽  
Vol 21 (11) ◽  
pp. 4090
Author(s):  
Sophia J. Lang ◽  
Michael Schmiech ◽  
Susanne Hafner ◽  
Christian Paetz ◽  
Katharina Werner ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
High Performance ◽  
Triple Negative ◽  
Artemisia Annua ◽  
Human Breast ◽  
Mitochondrial Membrane Potential Loss

Triple negative human breast cancer (TNBC) is an aggressive cancer subtype with poor prognosis. Besides the better-known artemisinin, Artemisia annua L. contains numerous active compounds not well-studied yet. High-performance liquid chromatography coupled with diode-array and mass spectrometric detection (HPLC-DAD-MS) was used for the analysis of the most abundant compounds of an Artemisia annua extract exhibiting toxicity to MDA-MB-231 TNBC cells. Artemisinin, 6,7-dimethoxycoumarin, arteannuic acid were not toxic to any of the cancer cell lines tested. The flavonols chrysosplenol d and casticin selectively inhibited the viability of the TNBC cell lines, MDA-MB-231, CAL-51, CAL-148, as well as MCF7, A549, MIA PaCa-2, and PC-3. PC-3 prostate cancer cells exhibiting high basal protein kinase B (AKT) and no ERK1/2 activation were relatively resistant, whereas MDA-MB-231 cells with high basal ERK1/2 and low AKT activity were more sensitive to chrysosplenol d treatment. In vivo, chrysosplenol d and casticin inhibited MDA-MB-231 tumor growth on chick chorioallantoic membranes. Both compounds induced mitochondrial membrane potential loss and apoptosis. Chrysosplenol d activated ERK1/2, but not other kinases tested, increased cytosolic reactive oxygen species (ROS) and induced autophagy in MDA-MB-231 cells. Lysosomal aberrations and toxicity could be antagonized by ERK1/2 inhibition. The Artemisia annua flavonols chrysosplenol d and casticin merit exploration as potential anticancer therapeutics.

scholarly journals Cytostatic Effect of a Novel Mitochondria-Targeted Pyrroline Nitroxide in Human Breast Cancer Lines

2021 ◽  
Vol 22 (16) ◽  
pp. 9016
Author(s):  
Kitti Andreidesz ◽  
Aliz Szabo ◽  
Dominika Kovacs ◽  
Balazs Koszegi ◽  
Viola Bagone Vantus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Human Breast Cancer ◽  
Triple Negative ◽  
Breast Cancer Cell Lines ◽  
Human Breast ◽  
Atp Production ◽  
Mitochondrial Functions

Mitochondria have emerged as a prospective target to overcome drug resistance that limits triple-negative breast cancer therapy. A novel mitochondria-targeted compound, HO-5114, demonstrated higher cytotoxicity against human breast cancer lines than its component-derivative, Mito-CP. In this study, we examined HO-5114′s anti-neoplastic properties and its effects on mitochondrial functions in MCF7 and MDA-MB-231 human breast cancer cell lines. At a 10 µM concentration and within 24 h, the drug markedly reduced viability and elevated apoptosis in both cell lines. After seven days of exposure, even at a 75 nM concentration, HO-5114 significantly reduced invasive growth and colony formation. A 4 h treatment with 2.5 µM HO-5114 caused a massive loss of mitochondrial membrane potential, a decrease in basal and maximal respiration, and mitochondrial and glycolytic ATP production. However, reactive oxygen species production was only moderately elevated by HO-5114, indicating that oxidative stress did not significantly contribute to the drug’s anti-neoplastic effect. These data indicate that HO-5114 may have potential for use in the therapy of triple-negative breast cancer; however, the in vivo toxicity and anti-neoplastic effectiveness of the drug must be determined to confirm its potential.

scholarly journals Phytochemicals inhibit migration of triple negative breast cancer cells by targeting kinase signaling

BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Pradip Shahi Thakuri ◽  
Megha Gupta ◽  
Sunil Singh ◽  
Ramila Joshi ◽  
Eric Glasgow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Protein Kinases ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Migration And Invasion ◽  
Tnbc Cell

Abstract Background Cell migration and invasion are essential processes for metastatic dissemination of cancer cells. Significant progress has been made in developing new therapies against oncogenic signaling to eliminate cancer cells and shrink tumors. However, inherent heterogeneity and treatment-induced adaptation to drugs commonly enable subsets of cancer cells to survive therapy. In addition to local recurrence, these cells escape a primary tumor and migrate through the stroma to access the circulation and metastasize to different organs, leading to an incurable disease. As such, therapeutics that block migration and invasion of cancer cells may inhibit or reduce metastasis and significantly improve cancer therapy. This is particularly more important for cancers, such as triple negative breast cancer, that currently lack targeted drugs. Methods We used cell migration, 3D invasion, zebrafish metastasis model, and phosphorylation analysis of 43 protein kinases in nine triple negative breast cancer (TNBC) cell lines to study effects of fisetin and quercetin on inhibition of TNBC cell migration, invasion, and metastasis. Results Fisetin and quercetin were highly effective against migration of all nine TNBC cell lines with up to 76 and 74% inhibitory effects, respectively. In addition, treatments significantly reduced 3D invasion of highly motile TNBC cells from spheroids into a collagen matrix and their metastasis in vivo. Fisetin and quercetin commonly targeted different components and substrates of the oncogenic PI3K/AKT pathway and significantly reduced their activities. Additionally, both compounds disrupted activities of several protein kinases in MAPK and STAT pathways. We used molecular inhibitors specific to these signaling proteins to establish the migration-inhibitory role of the two phytochemicals against TNBC cells. Conclusions We established that fisetin and quercetin potently inhibit migration of metastatic TNBC cells by interfering with activities of oncogenic protein kinases in multiple pathways.

Clomiphene Analogs with Activity In Vitro and In Vivo against Human Breast Cancer Cells

1998 ◽  
Vol 55 (6) ◽  
pp. 841-851 ◽  
Author(s):  
R.Jeffrey Baumann ◽  
Tammy L. Bush ◽  
Doreen E. Cross-Doersen ◽  
Elizabeth A. Cashman ◽  
Paul S. Wright ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast

scholarly journals Mead acid inhibits the growth of KPL-1 human breast cancer cells in vitro and in vivo

2014 ◽  
Vol 32 (4) ◽  
pp. 1385-1394 ◽  
Author(s):  
YUICHI KINOSHITA ◽  
KATSUHIKO YOSHIZAWA ◽  
KEI HAMAZAKI ◽  
YUKO EMOTO ◽  
TAKASHI YURI ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Mead Acid

scholarly journals α-Tocopherol succinate enhances pterostilbene anti-tumor activity in human breast cancer cells in vivo and in vitro

Oncotarget ◽  
2017 ◽  
Vol 9 (4) ◽  
pp. 4593-4606 ◽  
Author(s):  
Ka-Wai Tam ◽  
Chi-Tang Ho ◽  
Shih-Hsin Tu ◽  
Wen-Jui Lee ◽  
Ching-Shui Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Human Breast Cancer Cells ◽  
Human Breast ◽  
Anti Tumor Activity
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