scholarly journals Christia Vespertilionis Extract Induced Antiproliferation and Apoptosis in Breast Cancer (MCF7) Cells

2021 ◽  
Author(s):  
Noor Zafirah Ismail ◽  
Ismail Abiola Adebayo ◽  
Wan Ahmad Syazani Mohamed ◽  
Nur Nadhirah Mohamad Zain ◽  
Hasni Arsad
Keyword(s):  
Breast Cancer ◽  
Annexin V ◽  
Fold Increase ◽  
Antiproliferative Effect ◽  
Gas Chromatography Mass Spectrometry ◽  
Mcf7 Cells ◽  
Sulforhodamine B ◽  
Polymerase Chain ◽  
Apoptotic Genes ◽  
Molecular Genes

Abstract Background: C. vespertiliomis extracts were evaluated for antiproliferative and apoptosis effect on breast cancer (MCF7) cells. Methods and Results: The leaves extracts were analysed for its antiproliferative effect on breast cancer (MCF7) cells and normal epithelial breast (MCF 10A) cells using Sulforhodamine B (SRB) assay. The selective extract was evaluated for its ability to induce apoptosis using Annexin V-FITC apoptosis staining and the expression of molecular genes using qualitative reverse transcription-polymerase chain reaction (RT-PCR) against MCF7 cells. Gas chromatography–mass spectrometry (GC–MS) was used to identify the compounds from the selective extract. The findings showed that dichloromethane fraction (CV-Dcm) extract had high antiproliferative effect against MCF7 cells (IC50 = 24 µg/mL, selective index (SI) = 8.17). The percentages of apoptosis cells in CV-Dcm-treated MCF7 cells was 58.8%. The CV-Dcm extract induced downregulation of PCNA level. The apoptotic genes were also triggered in both extrinsic and intrinsic signaling pathways, affecting a 1.5-fold increase in BAX, 1.4-fold increase in cytochrome c, 1.3-fold increase in caspase-8, 1.7-fold increase in caspase-3 and 0.5-fold-decrease in BCL-2. Treated MCF7 cells also activated P53-dependent apoptotic death pathway. Conclusions: The present work strongly suggests that high efficacy of CV-Dcm extract was attributed to its antiproliferative and apoptosis-inducing activation in MCF7 cells, most likely due to its favourable compounds.

scholarly journals Epigenetic Immunomodulatory effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells

2020 ◽  
Author(s):  
Mariam A. Fouad ◽  
Mohamed M. Sayed-Ahmed ◽  
Etimad A. Huwait ◽  
Hafez F. Hafez ◽  
Abdel-Moneim Mahmoud Osman
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Functional Assay ◽  
Mcf7 Cells ◽  
Histone Acetyl Transferase ◽  
Immunological Markers ◽  
Epidermal Growth ◽  
Induced Apoptosis

Abstract Background: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to investigate the molecular mechanism (s) whereby EUG and AST could enhance DOX cytotoxicity in MCF7 cells.Methods: Cytotoxic activity of DOX alone and combined with either 1mM EUG or 40µM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results: DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1mM EUG or 40 µM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 µM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion: EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.

scholarly journals Senescent Colon and Breast Cancer Cells Induced by Doxorubicin Exhibit Enhanced Sensitivity to Curcumin, Caffeine, and Thymoquinone

2020 ◽  
Vol 19 ◽  
pp. 153473541990116 ◽  
Author(s):  
Ali H. El-Far ◽  
Noureldien H. E. Darwish ◽  
Shaker A. Mousa
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cellular Senescence ◽  
Annexin V ◽  
Mcf7 Cells ◽  
Enhanced Sensitivity ◽  
Cycle Arrest

Cellular senescence is a process of physiological growth arrest that can be induced by intrinsic or extrinsic stress signals. Some cancer therapies are associated with senescence of cancer cells with a typical cell cycle arrest. Doxorubicin (Dox) induces senescence by a p53-dependent pathway and telomere dysfunction of numerous cancers. However, cellular senescence induces suppression in proliferation activity, and these cells will remain metabolically active and play an important role in tumor relapse and development of drug resistance. In the current study, we investigated the apoptotic effect of curcumin (Cur), caffeine (Caff), and thymoquinone (TQ) on senescent colon cancer HCT116 and breast cancer MCF7 cell lines treated with Dox. Results showed typical senescence markers including decreased bromodeoxyuridine incorporation, increased accumulation of senescence-associated β-galactosidase (SA-β-gal), cell cycle arrest, and upregulation of p53, P-p53, and p21 proteins. Annexin-V analysis by flow cytometry revealed 2- to 6-fold increases in annexin-V–positive cells in Dox-treated MCF7 and HCT116 cells by Cur (15 µM), Caff (10 mM), and TQ (50 µM; P < .001). In comparison between proliferative and senescent of either HCT116 or MCF7 cells, Caff at 15 mM and TQ at 25 µM induced significant increases in apoptosis of Dox-treated cells compared with proliferative cells ( P < .001). Data revealed that Cur, Caff, and TQ potentially induced apoptosis of both proliferative and senescent HCT116 and MCF7 cells. In vivo and clinical trials are of great importance to validate this result.

scholarly journals Marine-Inspired Bis-indoles Possessing Antiproliferative Activity against Breast Cancer; Design, Synthesis, and Biological Evaluation

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 190 ◽  
Author(s):  
Wagdy M. Eldehna ◽  
Ghada S. Hassan ◽  
Sara T. Al-Rashood ◽  
Hamad M. Alkahtani ◽  
Abdulrahman A. Almehizia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Annexin V ◽  
Fold Increase ◽  
Biological Evaluation ◽  
Design Synthesis ◽  
Lead Compounds ◽  
M Phase ◽  
Indole Series ◽  
Induced Apoptosis ◽  
Mcf 7

Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a–f and 9a–h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 μM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%–58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.

scholarly journals Epigenetic Immunomodulatory effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells

2020 ◽  
Author(s):  
Mariam A. Fouad ◽  
Mohamed M. Sayed-Ahmed ◽  
Etimad A. Huwait ◽  
Hafez F. Hafez ◽  
Abdel-Moneim Osman
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Functional Assay ◽  
Mcf7 Cells ◽  
Histone Acetyl Transferase ◽  
Epidermal Growth ◽  
Induced Apoptosis

Abstract Background: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to improve the cytotoxic activity and reduce resistance of DOX through combination with EUG and AST in MCF7 cells.Methods: Cytotoxic activity of DOX alone and combined with either 1mM EUG or 40µM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results: DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1mM EUG or 40 µM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 µM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion: EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.

scholarly journals Epigenetic immunomodulatory effect of eugenol and astaxanthin on doxorubicin cytotoxicity in hormonal positive breast Cancer cells

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Mariam A. Fouad ◽  
Mohamed M. Sayed-Ahmed ◽  
Etimad A. Huwait ◽  
Hafez F. Hafez ◽  
Abdel-Moneim M. Osman
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Functional Assay ◽  
Mcf7 Cells ◽  
Histone Acetyl Transferase ◽  
Immunological Markers ◽  
Epidermal Growth ◽  
Induced Apoptosis

Abstract Background Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to investigate the molecular mechanism (s) whereby EUG and AST could enhance DOX cytotoxicity in MCF7 cells. Methods Cytotoxic activity of DOX alone and combined with either 1 mM EUG or 40 μM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1 mM EUG or 40 μM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 μM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.

scholarly journals Epigenetic Immunomodulatory Effect of Eugenol and Astaxanthin on Doxorubicin Cytotoxicity in Hormonal Positive Breast Cancer Cells

2020 ◽  
Author(s):  
Mariam A. Fouad ◽  
Mohamed M. Sayed-Ahmed ◽  
Etimad A. Huwait ◽  
Hafez F. Hafez ◽  
Abdel-Mneim M. Osman
Keyword(s):  
Breast Cancer ◽  
Cytotoxic Activity ◽  
Molecular Subtype ◽  
Growth Factor Receptor ◽  
Annexin V ◽  
Functional Assay ◽  
Mcf7 Cells ◽  
Histone Acetyl Transferase ◽  
Epidermal Growth ◽  
Induced Apoptosis

Abstract Background: Hormonal receptor positive (HR+) breast cancer is the most commonly diagnosed molecular subtype of breast cancer; which showed good response to doxorubicin (DOX)-based chemotherapy. Eugenol (EUG) and astaxanthin (AST) are natural compounds with proved epigenetic and immunomodulatory effects in several cancer cell lines. This study has been initiated to improve the cytotoxic activity and reduce resistance of DOX through combination with EUG and AST in MCF7 cells.Methods: Cytotoxic activity of DOX alone and combined with either 1mM EUG or 40µM AST was performed using sulphorhodamine-B assay in MCF7 cells. Global histones acetylation and some immunological markers were investigated using ELISA, western blotting and quantitative RT-PCR techniques. Functional assay of multidrug resistance was performed using rhodamine 123 and Hoechst 3342 dyes. Flow cytometry with annexin V and propidium iodide were used to assess the change in cell cycle and apoptosis along with the expression of some differentiation, apoptosis and autophagy proteins. Results: DOX alone resulted in concentration-dependent cytotoxicity with IC50 of 0.5 μM. Both EUG and AST significantly increased DOX cytotoxicity which is manifested as a significant decrease in DOX IC50 from 0.5 μM to 0.088 μM with EUG and to 0.06 μM with AST. Combinations of DOX with 1mM EUG or 40 µM AST significantly increased the level of histones acetylation and histone acetyl transferase expression, while reduced the expression of aromatase and epidermal growth factor receptor (EGFR) when compared with 0.25 µM DOX alone. Also both combinations showed higher uptake of rhodamine but lower of Hoechst stains, along with increased the percentage of caspase 3, and decreased the expression of CK7 and LC3BI/II ratio. EUG combination induced IFγ but reduced TNFα causing shifting of cells from G2/M to S and G0/ G1 phases. Combination of DOX with EUG induced apoptosis through the higher BAX/ BCl2 ratio, while with AST was through the increase in caspase 8 expressions. Conclusion: EUG and AST potentiated the anticancer activity of DOX through epigenetic histones acetylation along with the immunonomodulation of different apoptotic approaches in MCF7 cells.

scholarly journals Clinacanthus Nutans Induces Antiproliferative and Apoptosis in Human Breast Cancer Cells Through Targeted Apoptosis Pathway

2022 ◽  
Author(s):  
Hasni Arsad ◽  
Noor Zafirah Ismail ◽  
Salwani Md S ◽  
Ismail Abiola Adebayo ◽  
Zaleha Md T ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Molecular Mechanisms ◽  
Annexin V ◽  
Mcf7 Cells ◽  
Apoptosis Pathway ◽  
Qualitative Polymerase Chain Reaction ◽  
Flight Mass Spectrometry ◽  
Clinacanthus Nutans ◽  
Induced Apoptosis

Abstract Clinacanthus nutans dichloromethane fraction (CN-Dcm) extract has previously been proven to suppress breast cancer (MCF7) cell proliferation. Despite this, the molecular mechanisms involved in C. nutans extract-treated MCF7 cells are unknown. Hence, the molecular mechanism of apoptosis in treated MCF7 was investigated in this current study. This study was intended to subfractionate CN-Dcm extract using column chromatography and analysed the treated MCF7 cells using the CellTiter 96® AQueous One Solution Cell Proliferation (MTS) assay, Annexin V/propidium iodide (PI) assay, western blot and reverse transcription-qualitative polymerase chain reaction (RT-qPCR). Out of nine subfraction extracts (SF1 to SF9), SF2 extract strongly inhibited MCF7 cells with the lowest IC50 value (23.51 ± 0.99 µg/mL) and substantially induced apoptosis in the MCF7 cells. SF2 extract significantly downregulated BCL-2 expression and upregulated P53, BAX, BID, BCL-2, caspase-8, caspase-9 and caspase-3 expressions in treated MCF7 cells. Therefore, SF2 extract was analysed using liquid chromatography coupled to quadrupole time–of–flight mass spectrometry (LC-QTOF-MS), which confirmed the presence of bioactive chemical compounds. Thus, it can be concluded that the compounds found in SF2 extract may potentially cause apoptosis in MCF7 cells through intrinsic and extrinsic pathways.

scholarly journals Expression of somatostatin receptors subtypes (1-5) mRNA in MCF7 and MDA-MB231 breast cancer human cell lines

2020 ◽  
Author(s):  
ALKHANSA MAHMOUD ◽  
Maria Teresa Mancuso ◽  
Barbara Tanno ◽  
Zuki Abu Bakar ◽  
Hazilawati Hamzah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mrna Expression ◽  
Cell Lines ◽  
Quantitative Polymerase Chain Reaction ◽  
Somatostatin Receptors ◽  
Breast Cancer Cell Lines ◽  
Mrna Levels ◽  
Mcf7 Cells ◽  
Polymerase Chain ◽  
Mcf 7

Abstract Background: breast cancer is one of most common types of cancer and heterogeneous disease. Somatostatain receptors (SSTR1-5) are expressed in breast cancer cells. MCF7 and MDA-MB231 cell lines used to evaluate the expression of somatostatin receptors (SSTRs 1 - 5). Methods: The detection of mRNA expression levels of SSTRs in MCF7 and MDA-MB231 was performed using quantitative- polymerase chain reaction (qPCR). Results: All SSTRs 1 - 5 were expressed in both cells lines. The SSTR 1, 2, 3 and 4 mRNA levels were significantly higher in MDA-MB-231 in relation to MCF-7. The expression of SSTR 4 and 5 mRNA was highest in MDA-MB231 and MCF-7 cell lines respectively, however, SSTR3 mRNA was least expressed in both cell lines. Conclusion: All SSTRs were expressed in both MDA-MB231 and MCF7 cells. However, the levels of expression differ between both cell lines. Keywords: Breast cancer. Cell lines .Somatostatin receptors. mRNA expression

Combination of Histone Deacetylase Inhibitor with Cu(II) 5,5- diethylbarbiturate Complex Induces Apoptosis in Breast Cancer Stem Cells: A Promising Novel Approach

2020 ◽  
Vol 21 ◽  
Author(s):  
Merve Erkisa ◽  
Nazlihan Aztopal ◽  
Elif Erturk ◽  
Engin Ulukaya ◽  
Veysel T. Yilmaz ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oxidative Stress ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Histone Deacetylases ◽  
Caspase 3 ◽  
Cancer Cell Line ◽  
Annexin V ◽  
Tumor Formation ◽  
Dependent Manner

Background: Cancer stem cells (CSC) are subpopulation within the tumor that acts a part in the initiation, progression, recurrence, resistance to drugs and metastasis of cancer. It is well known that epigenetic changes lead to tumor formation in cancer stem cells and show drug resistance. Epigenetic modulators and /or their combination with different agents have been used in cancer therapy. Objective: In our study we scope out the effects of combination of a histone deacetylases inhibitor, valproic acid (VPA), and Cu(II) complex [Cu(barb-κN)(barb-κ2N,O)(phen-κN,N’)]·H2O] on cytotoxicity/apoptosis in a stem-cell enriched population (MCF-7s) obtained from parental breast cancer cell line (MCF-7). Methods: Viability of the cells was measured by the ATP assay. Apoptosis was elucidated via the assessment of caspase-cleaved cytokeratin 18 (M30 ELISA) and a group of flow cytometry analysis (caspase 3/7 activity, phosphatidylserine translocation by annexin V-FITC assay, DNA damage and oxidative stress) and 2ˈ,7ˈ–dichlorofluorescein diacetate staining. Results: The VPA combined with Cu(II) complex showed anti proliferative activity on MCF-7s cells in a dose- and time-dependently. Treatment with combination of 2.5 mM VPA and 3.12 μM Cu(II) complex induces oxidative stress in a time-dependent manner, as well as apoptosis that is evidenced by the increase in caspase 3/7 activity, positive annexin-V-FITC, and increase in M30 levels. Conclusion: The results suggest that the combination therapy induces apoptosis following increased oxidative stress, thereby making it a possible promising therapeutic strategy that further analysis is required.

Antitumor Activity and Underlying Mechanism of Phomoxanthone B in MCF7 Cells

2020 ◽  
Vol 20 ◽  
Author(s):  
Chuan Chen ◽  
Ziyue Zhao ◽  
Qian Dong ◽  
XueHui Gao ◽  
Huibin Xu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Antitumor Activity ◽  
Oxidative Phosphorylation ◽  
Tumor Cells ◽  
Transcriptome Analysis ◽  
Mcf7 Cells ◽  
Er Positive ◽  
Induced Apoptosis ◽  
Positive Breast Cancer

Background:: Xanthones are a class of heterocyclic natural products, which are promising sources of anticancer leads. Phomoxanthone B（PXB）and Phomoxanthone A（PXA）are xanthone dimers. PXA is well studied as an anti-cancer agent, but PXB is not. In our study, PXB was isolated from the endophytic fungus Phomopsis sp. By254. Objective:: The purpose of this study was to identify the underlying anti-tumor mechanisms of PXB in breast cancer MCF7 cell line. Methods:: Apoptosis, cell cycle, proliferation, invasion and migration assays were used to assess the antitumor activity of PXB. RNA sequencing was used to analyze the effect of PXB treatment on gene expression in MCF7 cells. Results:: PXB showed cytotoxicity toward a variety of tumor cells, especially MCF7 cells. PXB inhibited the migration and invasion, arrested cell cycle at G2/M phase and induced apoptosis associated with caspase-3 activation in MCF7 cells. The detailed transcriptome analysis revealed that PXB affected several pathways related to tumorigenesis, metabolisms-, and oxidative phosphorylation in MCF7 cells. KEGG transcriptome analysis revealed that PXB upregulated pro-survival signal pathways such as MAPK, PI3K-AKT and STAT3 pathways. We found that PXB also significantly upregulated the expression of IL24, DDIT3 and XAF1, which may contribute to PXB-induced apoptosis. We further found that PXB may downregulate oxidative phosphorylation by decreasing the expression of electron transport chain genes, especially MT-ND1, which is a potential unfavorable prognostic marker for ER-positive breast cancer. Conclusion:: PXB exerts strong cytotoxicity against human tumor cells and has a potential for ER-positive breast cancer treatment.

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