Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells

Ko, Yu Min; Wu, Tung Ying; Wu, Yang Chang; Chang, Fang Rong; Guh, Jinn Yuh; Chuang, Lea Yea

doi:10.1016/j.jep.2011.07.056

Cited by 60 publications

(44 citation statements)

References 32 publications

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“…An in‐vitro study demonstrated a drug and metabolic enzyme interaction that resulted in an additive effect of annonacin to 4‐hydroxytamoxifen through the inhibition of MCF‐7 breast cancer cell line survival . An additive anti‐inflammatory effect between oral aqueous A. muricata leaf extract and aspirin was demonstrated in a mice model study at a dose of 100 mg/kg .…”

Section: Resultsmentioning

confidence: 99%

The safety and tolerability of Annona muricata leaf extract: a systematic review

Chan

McLachlan

Hanrahan

et al. 2020

Journal of Pharmacy and Pharmacology

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Objectives Annona muricata, also known as graviola, soursop and guanabana, has been widely utilised for the treatment of a range of cancers. The mechanism of action and the efficacy of A. muricata and its constituents in the treatment of cancer have been comprehensively reviewed. The aim of this systematic review was to summarise the available literature that reports on factors related to the safety and tolerability of A. muricata leaf extract and its acetogenins. Methods In‐vitro, preclinical animal studies and human studies of any design written in any language were included. Studies that evaluated A. muricata leaf extract and its constituents were searched through the databases Pubmed, Medline and Embase from inception to April 2019. The elaborated item 4 of Consolidated Standards of Reporting Trials statement and Animals in Research: Reporting In vivo Experiments guidelines were used to evaluate the quality of the studies. Key findings The results suggest that A. muricata and its constituents have hepatoprotective, neurotoxic, antinociceptive, anti‐ulcerative and chemopreventive effects. The dose and duration used in animal studies demonstrating toxicity may not directly translate into the effects in humans. Studies included in this review were judged to be of medium to high quality. Conclusions The overall outcome of the current review suggests that A. muricata has a favourable safety and tolerability profile. Future studies investigating its use in people diagnosed with a range of cancers are warranted.

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Section: Resultsmentioning

confidence: 99%

The safety and tolerability of Annona muricata leaf extract: a systematic review

Chan

McLachlan

Hanrahan

et al. 2020

Journal of Pharmacy and Pharmacology

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“…Moreover, equol and tamoxifen induced a time-dependent reduction in blc-2 expression and hence the bcl-2:bax ratio, which was further reduced by the combination of the two compounds (Figure 6). Decreased bcl-2 expression was observed in several cancer cell types treated with tamoxifen and daidzein [14,63,64] and in equol-induced apoptosis in mammary carcinomas [14,48]. …”

Section: Discussionmentioning

confidence: 99%

Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells

2013

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BackgroundSoy phytoestrogens, such as daidzein and its metabolite equol, have been proposed to be responsible for the low breast cancer rate in Asian women. Since the majority of estrogen receptor positive breast cancer patients are treated with tamoxifen, the basic objective of this study is to determine whether equol enhances tamoxifen’s anti-tumor effect, and to identify the molecular mechanisms involved.MethodsFor this purpose, we examined the individual and combined effects of equol and tamoxifen on the estrogen-dependent MCF-7 breast cancer cells using viability assays, annexin-V/PI staining, cell cycle and western blot analysis.ResultsWe found that equol (>50 μM) and 4-hydroxy-tamoxifen (4-OHT; >100 nM) significantly reduced the MCF-7 cell viability. Furthermore, the combination of equol (100 μM) and 4-OHT (10 μM) induced apoptosis more effectively than each compound alone. Subsequent treatment of MCF-7 cells with the pan-caspase inhibitor Z-VAD-FMK inhibited equol- and 4-OHT-mediated apoptosis, which was accompanied by PARP and α-fodrin cleavage, indicating that apoptosis is mainly caspase-mediated. These compounds also induced a marked reduction in the bcl-2:bax ratio, which was accompanied by caspase-9 and caspase-7 activation and cytochrome-c release to the cytosol. Taken together, these data support the notion that the combination of equol and tamoxifen activates the intrinsic apoptotic pathway more efficiently than each compound alone.ConclusionsConsequently, equol may be used therapeutically in combination treatments and clinical studies to enhance tamoxifen’s effect by providing additional protection against estrogen-responsive breast cancers.

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“…The antitumor properties of annonacin (Fig. ) were tested in MCF‐7 xenografts in nude mice . In an ERα + MCF‐7 cell line, annonacin (half‐effective dose (ED 50 ) of 0.31 μM) and 4‐hydroxytamoxifen (ED 50 of 1.13 μM) decreased cell survival.…”

Section: Annonaceous Acetogeninsmentioning

confidence: 99%

Annona species (Annonaceae): a rich source of potential antitumor agents?

Tundis

Xiao

Loizzo

2017

Annals of the New York Academy of Sciences

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Plants have provided the basis of traditional medicine systems throughout the world for thousands of years and continue to yield molecules for new remedies. We analyzed studies published from 2009 to 2016 on the Annona species (Annonaceae), including A. coriacea, A. crassifolia, A. hypoglauca, A. muricata, A. squamosa, A. sylvatica, and A. vepretorum, as sources of potential antitumor agents. Here, we report and discuss the mechanisms of action and structure-activity relationships of the most active Annona constituents. Annonaceous acetogenins are one of the most promising classes of natural products, owing to their potential antitumor activity. However, their neurotoxicity should not be underestimated.

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Annonacin induces cell cycle-dependent growth arrest and apoptosis in estrogen receptor-α-related pathways in MCF-7 cells

Cited by 60 publications

References 32 publications

The safety and tolerability of Annona muricata leaf extract: a systematic review

The safety and tolerability of Annona muricata leaf extract: a systematic review

Equol enhances tamoxifen’s anti-tumor activity by induction of caspase-mediated apoptosis in MCF-7 breast cancer cells

Annona species (Annonaceae): a rich source of potential antitumor agents?

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