Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells

Ren, Guowen; Sha, Tongye; Guo, Jiajie; Li, Wenxue; Lu, Jin‐Jian; Chen, Xiuping

doi:10.1007/s11418-015-0918-4

Cited by 50 publications

(31 citation statements)

References 47 publications

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“…Increased LDH release suggested that Cuc B might affect cell membrane. We previously reported that Cuc B induced DNA damage in A549 [27], K562 [23], and MCF-7 cells [28]. Cuc B induced long tails in comet assay and increased γ -H 2 AX expression suggesting that it induced DNA damage in BEL-7402 cells.…”

Section: Discussionmentioning

confidence: 99%

“…MDC staining used to detect the formation of acidic vesicular organelles in Cuc B-treated cells was performed as in our previous reports [28, 34]. …”

Section: Methodsmentioning

confidence: 99%

“…The underlying mechanisms include inhibition of JAK/STAT3 [20, 24, 25], induction of DNA damage [23], generation of ROS [26], reduction of G-actin, and activation of cofilin [22]. We firstly reported that Cuc B induced DNA damage mediated by ROS in A549, K562, and MCF-7 cells [23, 27, 28]. Cuc B also induced protective autophagy in HeLa [29], Jurkat [22], MCF-7 [28], and B16F10 cells [30].…”

Section: Introductionmentioning

confidence: 99%

“…We firstly reported that Cuc B induced DNA damage mediated by ROS in A549, K562, and MCF-7 cells [23, 27, 28]. Cuc B also induced protective autophagy in HeLa [29], Jurkat [22], MCF-7 [28], and B16F10 cells [30]. Furthermore, Cuc E-, Cuc D-, and Cuc I-induced autophagy was also documented in various cancer cell lines and normal cells [31–35].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore, Cuc E-, Cuc D-, and Cuc I-induced autophagy was also documented in various cancer cell lines and normal cells [31–35]. Similarly, the underlying mechanisms involve ROS generation and STAT3 inhibition [28, 29, 34, 36]. Interestingly, cucurbitacins-induced autophagy acts as a prosurvival effect [32, 34].…”

Section: Introductionmentioning

confidence: 99%

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PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells

Niu

Sun

et al. 2016

Oxidative Medicine and Cellular Longevity

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Cucurbitacin B (Cuc B), a natural product, induced both protective autophagy and DNA damage mediated by ROS while the detailed mechanisms remain unclear. This study explored the mechanism of Cuc B-induced DNA damage and autophagy. Cuc B decreased cell viability in concentration- and time-dependent manners. Cuc B caused long comet tails and increased expression of γ-H2AX, phosphorylation of ATM/ATR, and Chk1/Chk2. Cuc B induced autophagy as evidenced by monodansylcadaverine (MDC) staining, increased expression of LC3II, phosphorylated ULK1, and decreased expression of phosphorylated AKT, mTOR. Cuc B induced apoptosis mediated by Bcl-2 family proteins and caspase activation. Furthermore, Cuc B induced ROS formation, which was inhibited by N-acetyl-L-cysteine (NAC). NAC pretreatment dramatically reversed Cuc B-induced DNA damage, autophagy, and apoptosis. Cuc B-induced apoptosis was reversed by NAC but enhanced by 3-methyladenine (3-MA), chloroquine (CQ), and silencing phosphatase and tensin homolog (PTEN). 3-MA and CQ showed no effect on Cuc B-induced DNA damage. In addition, Cuc B increased PTEN phosphorylation and silence PTEN restored Cuc B-induced autophagic protein expressions without affecting DNA damage. In summary, Cuc B induced DNA damage, apoptosis, and protective autophagy mediated by ROS. PTEN activation in response to DNA damage bridged DNA damage and prosurvival autophagy.

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Section: Discussionmentioning

confidence: 99%

“…MDC staining used to detect the formation of acidic vesicular organelles in Cuc B-treated cells was performed as in our previous reports [28, 34]. …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells

Niu

Sun

et al. 2016

Oxidative Medicine and Cellular Longevity

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Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy

Yang

Zheng

et al. 2017

J of Cellular Biochemistry

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Lack of effective anti-cardiac hypertrophy drugs creates a major cause for the increasing prevalence of heart failure. In the present study, we determined the anti-hypertrophy and anti-fibrosis potential of a natural plant triterpenoid, Cucurbitacin B both in vitro and in vivo. Aortic banding (AB) was performed to induce cardiac hypertrophy. After 1 week of surgery, mice were receive cucurbitacin B treatment (Gavage, 0.2 mg/kg body weight/2 day). After 4 weeks of AB, cucurbitacin B demonstrated a strong anti-hypertrophy and -fibrosis ability as evidenced by decreased of heart weight, myocardial cell cross-sectional area and interstitial fibrosis, ameliorated of systolic and diastolic abnormalities, normalized in gene expression of hypertrophic and fibrotic markers, reserved microvascular density in pressure overload induced hypertrophic mice. Cucurbitacin B also showed significant hypertrophy inhibitory effect in phenylephrine stimulated cardiomyocytes. The Cucurbitacin B-mediated mitigated cardiac hypertrophy was attributable to the increasing level of autophagy, which was associated with the blockade of Akt/mTOR/FoxO3a signal pathway, validated by SC79, MK2206, and 3-MA, the Akt agonist, inhibitor and autophagy inhibitor in vitro. The overexpression of constitutively active Akt completely abolished the Cucurbitacin B-mediated protection of cardiac hypertrophy in human cardiomyocytes AC16. Collectively, our findings suggest that cucurbitacin B protects against cardiac hypertrophy through increasing the autophagy level in cardiomyocytes, which is associated with the inhibition of Akt/mTOR/FoxO3a signal axis. J. Cell. Biochem. 118: 3899-3910, 2017. © 2017 Wiley Periodicals, Inc.

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Chemical Composition Analysis and In Vitro Investigation of Cytotoxic and Antioxidative Activities of Iranian Propolis against Breast Cancer Cell Line, MCF‐7

Asgharpour

Moghadamnia²,

Kazemi³

et al. 2018

ChemistrySelect

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Propolis is a natural resinous mixture found in beehives. It has pharmacological and biology properties, which are related to its chemical composition. In the current study, the chemical composition of ethanolic extract of Iranian propolis (EEIP) was determined through high‐performance liquid chromatography (HPLC). The radical scavenging activity of EEIP was evaluated through 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2′‐azino‐bis (3‐ethylbenzothiazoline‐6‐sulfonic acid (ABTS) along with ferric reducing ability power (FRAP) assay. In addition, the cytotoxic effects and intracellular capacity for reactive oxygen species (ROS) production of EEIP and individual components were evaluated on human breast cancer cell line, MCF‐7. Also, effects of EEIP on cell viability was measured on fibroblast as a normal cell line. The obtained results revealed high contents of total phenolics and flavonoids in the EEIP extracts. The bioactive compounds that were identified in the EEIP extracts included caffeic acid, quercetin, chrysin, galangin, and pinobanksin. The EEIP and polyphenols were cytotoxic for MCF‐7 cells and significantly tended to increase intracellular ROS production in a dose dependent manner. In contrast, EEIP had no cytotoxic effect on fibroblast cells. Taken together, we suggest that the synergistic effect of the main components of propolis is related to increase of ROS and inhibition of MCF‐7 cell proliferation.

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Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells

Cited by 50 publications

References 47 publications

PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells

PTEN Activation by DNA Damage Induces Protective Autophagy in Response to Cucurbitacin B in Hepatocellular Carcinoma Cells

Cucurbitacin B Protects Against Pressure Overload Induced Cardiac Hypertrophy

Chemical Composition Analysis and In Vitro Investigation of Cytotoxic and Antioxidative Activities of Iranian Propolis against Breast Cancer Cell Line, MCF‐7

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