9-Xanthone as a Novel Angiotensin Converting Enzyme 2 Activator: Context-Specific Chemistry in Breast Cancer

Q: What is the clinical evidence from this study?

Population: Breast Cancer. Intervention: 9-xanthone vs. l-carnosine (6.25 to 100 mg/ml) or untreated negative controls. Primary outcome: In vitro ACE2 enzymatic activity (RFU readings) and cell viability (% survival in MTT assay).

Zeena Shamil Attallah; Loai M. Saadah; Sara Melhem; Iman Mansi; Saja Hamed; Wamidh H. Talib

doi:10.35192/jjoas-n.v20i1.187

October 5, 2026Jordan Journal of Applied Science - Natural Science SeriesOpen Access

9-Xanthone as a Novel Angiotensin Converting Enzyme 2 Activator: Context-Specific Chemistry in Breast Cancer

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Key result

9-xanthone increases in vitro ACE2 activity by ~33%, triggering cell line-specific growth effects.

Why the study?

This study was conducted to evaluate 9-xanthone as an ACE2 activator, assess its effect on breast cancer cell line viability, and formulate a hypothesis for context-specific effects of ACE2 modulators in breast cancer, novel coronavirus, and nephrotoxicity.

Does 9-xanthone activate ACE2 and affect the viability of human and murine breast cancer cell lines in vitro?

Key Points

Evaluate 9-xanthone as a novel ACE2 activator and assess its context-specific impact on the viability of diverse breast cancer cell lines.
Measured ACE2 activity and expression in MCF-7, MDA-MB-231, and EMT-6 breast cancer cell lines using fluorometric activity assays and Bradford protein quantification.
Assessed cell viability via MTT assays across 9-xanthone concentrations ranging from approximately 1.6 µM to 500 µM in MCF-7, MDA-MB-231, EMT-6, and Vero cells.
Evaluated enzymatic modulation by testing 9-xanthone at concentrations of 9.4 to 150 µg/ml alone and in combination with L-carnosine at 6.25 to 100 mg/ml.
9-xanthone acted as a dose-dependent ACE2 activator at 50 to 750 µM, causing an average 33% increase over baseline ACE2 activity that was partially reversed by L-carnosine.
MCF-7 cell viability paradoxically increased in a dose-dependent manner from 71.1 ± 7.8% at 1.5625 µM to 495.4 ± 280.5% at 500 µM, with an EC50 of approximately 75 µM.
9-xanthone exhibited cytostatic effects on aggressive cell lines, reducing viability at 500 µM to 42.4 ± 4.6% in MDA-MB-231 and 36.4 ± 7.6% in EMT-6 cells.

Structured PICO

Does 9-xanthone activate ACE2 and affect the viability of human and murine breast cancer cell lines in vitro?

P

Population

In vitro experimental study evaluating human (MCF-7, MDA-MB-231) and murine (EMT-6) breast cancer cell lines as well as Vero cells incubated for up to 24 hours.

I

Intervention

9-xanthone at concentrations ranging from 2.3 to 150 µg/ml (11.8 to 765 µM) for ACE2 expression and activity assays (evaluated at 2 and 24 hours), and ~1.6 to 500 µM for 24 hours in MTT cell viability assays, with or without l-carnosine (6.25 to 100 mg/ml, or 27 to 434 mM).

C

Comparator

Untreated control cell lysates/lines and l-carnosine (an ACE2 inhibitor tested at 6.25 to 100 mg/ml [27 to 434 mM]).

O

Outcome

In vitro ACE2 enzymatic activity (measured in relative fluorescence units [RFU] and mU via fluorometric activity assay in cell pellets), ACE2 protein expression (measured via sandwich ELISA and optical density at 450 nm in supernatants/lysates at 2 and 24 hours), and cell viability/metabolic survival (measured via MTT assay at 24 hours).surrogate

Main Result

Absolute Event Rate: 911% vs 684%

In vitro, 9-xanthone acts as a mild dose-dependent ACE2 activator that promotes proliferation in luminal MCF-7 breast cancer cells while exerting cytostatic effects on triple-negative MDA-MB-231 and murine EMT-6 breast cancer cell lines.

Limitations

In vitro study using cell lines without in vivo animal or clinical validation due to logistical and funding constraints
Mechanistic confirmation relied largely on narrative literature review rather than direct experimental assays
Did not evaluate 9-xanthone in the presence and absence of specific ACE2 inhibitors in supernatants
Possible technical error in the ACE2 activity experiment for the EMT-6 cell line
High micromolar concentrations used in vitro limit direct translation into clinical practice
An in vivo experiment was not carried out with EMT-6 for logistic reasons.
Due to limited funding, mechanistic confirmation largely depended on literature review rather than experimental validation.
Did not evaluate 9-xanthone in the presence and absence of inhibitors in supernatants.
Potential technical error or unexplained absence of ACE2 activity difference in the EMT-6 cell line.
MCF-7 protein content was higher than MDA-MB-231 in the Bradford assay, which is inconsistent with previous reports.

Ask about this paper

Answers are grounded in this paper and cite their sources.

Implication

Should not change practice; hypothesis-generating for subtype-specific ACE2 effects in breast cancer.

Abstract

Background: Current study evaluates 9-xanthone as an ACE2 activator and its effect on viability of breast cancer cell lines. Finally, using a chemical narrative review, it formulates a hypothesis for context-specific effects of ACE2 modulators in breast cancer, novel coronavirus, and nephrotoxicity. Methods: ACE2 activation was confirmed using in vitro activity assay. Next, ACE2 expression after exposure to 9-xanthone was analyzed in the supernatant samples from breast cancer cell lines (MCF-7, MDA-MB-231, and EMT-6). Additionally, ACE2 activity was confirmed in cell line pellets using a fluorometric activity assay kit. Finally, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was carried out at the same concentration ranges. Results: 9-xanthone is a mild, dose-dependent, ACE2 activator at 50 to 750 µM. Carnosine, a mild ACE2 inhibitor, partially reverses this effect. ACE2 expression and viability for MCF-7 consistently rose at all doses between 2- and 24-hours post exposure. Similarly, 9-xanthone increased expression of EMT-6. However, the drug showed cytostatic effects on MDA-MB-231 and EMT-6 cell lines. Similar chemical structures consistently affected breast cancer activity, coronavirus infectivity, and nephrotoxicity. Conclusion: Further exploration of xanthones and ACE2 in breast cancer, novel coronavirus disease, and nephrotoxicity is much warranted.

Discussion

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Cite This Study

Attallah et al. (2026) studied Breast Cancer. 9-xanthone vs. l-carnosine (6.25 to 100 mg/ml) or untreated negative controls was evaluated on In vitro ACE2 enzymatic activity (RFU readings) and cell viability (% survival in MTT assay). 9-xanthone increased in vitro ACE2 activity by 33% at 50–750 µM, inducing pro-metabolic growth in MCF-7 cells (EC50 75 µM) and cytostatic effects in EMT-6 (IC50 6 µM) and MDA-MB-231 cells.

synapsesocial.com/papers/6ae28e0ecbadf70daf6c405e https://doi.org/10.35192/jjoas-n.v20i1.187

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9-Xanthone as a Novel Angiotensin Converting Enzyme 2 Activator: Context-Specific Chemistry in Breast Cancer

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

9-Xanthone as a Novel Angiotensin Converting Enzyme 2 Activator: Context-Specific Chemistry in Breast Cancer

Key Points

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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