Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-κB signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells

Ku, Jin Mo; Kim, Soon Re; Hong, Se Hyang; Choi, Han‐Seok; Seo, Hye Sook; Shin, Yong Cheol; Ko, Seong‐Gyu

doi:10.1007/s11010-015-2509-9

Cited by 67 publications

(49 citation statements)

References 29 publications

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“…Cucurbitacin B is found in many Cucurbitaceous plant species and is one of the abundant forms of cucurbitacins22. Cucurbitacin D is one of the analogue of cucurbitacins which has shown anti-cancer activity against various types of cancer2324252627. Most of the studies have revealed anti-cancer effects of Cucurbitacin D via induction of apoptosis and suppression of constitutive activation of NF-κB and STAT3.…”

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confidence: 99%

Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer

Sikander

Hafeez

Malik

et al. 2016

Sci Rep

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In this study, we for the first time, investigated the potential anti-cancer effects of a novel analogue of cucurbitacin (Cucurbitacin D) against cervical cancer in vitro and in vivo. Cucurbitacin D inhibited viability and growth of cervical cancer cells (CaSki and SiHa) in a dose-dependent manner. IC50 of Cucurbitacin D was recorded at 400 nM and 250 nM in CaSki and SiHa cells, respectively. Induction of apoptosis was observed in Cucurbitacin D treated cervical cancer cells as measured by enhanced Annexin V staining and cleavage in PARP protein. Cucurbitacin D treatment of cervical cancer cells arrested the cell cycle in G1/S phase, inhibited constitutive expression of E6, Cyclin D1, CDK4, pRb, and Rb and induced the protein levels of p21 and p27. Cucurbitacin D also inhibited phosphorylation of STAT3 at Ser727 and Tyr705 residues as well as its downstream target genes c-Myc, and MMP9. Cucurbitacin D enhanced the expression of tumor suppressor microRNAs (miR-145, miRNA-143, and miRNA34a) in cervical cancer cells. Cucurbitacin D treatment (1 mg/kg body weight) effectively inhibited growth of cervical cancer cells derived orthotopic xenograft tumors in athymic nude mice. These results demonstrate the potential therapeutic efficacy of Cucurbitacin D against cervical cancer.

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confidence: 99%

Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer

Sikander

Hafeez

Malik

et al. 2016

Sci Rep

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“…Stat3 activation is a predictive marker of drug resistance because it is linked to the development of doxorubicin resistance in cancer cell lines. 11,45,46 We found that cucurbitacin D decreased the levels of p-Akt and p-Stat3 in MCF7, MDA-MB-231, and SKBR3 cells. However, doxorubicin alone did not decrease p-Akt and p-Stat3 levels.…”

Section: Discussionmentioning

confidence: 73%

“…The MCF7 cell line has an induced upregulation of activated Stat3 and shows resistance to doxorubicin. [11][12][13] Signal transducers and activators of transcription (Stat) proteins are transcription factors. The Stat family is composed of Stats 1, 2, 3, 4, 5a, 5b, and 6.…”

Section: Introductionmentioning

confidence: 99%

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Cucurbitacin D exhibits its anti-cancer effect in human breast cancer cells by inhibiting Stat3 and Akt signaling

Hong

Kim

et al. 2018

Eur J Inflamm

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Cucurbitacins are triterpenoids commonly found in Cucurbitaceae and Cruciferae and have long been used in traditional medicine. Cucurbitacins demonstrate anti-inflammatory and anti-cancer activities. We investigated whether cucurbitacin D affects viability in breast cancer cells and its mechanism of action. An MTT assay was used to measure the viability of breast cancer cells. Western blot analysis was used to measure the expression of various modulators, such as p-p53, p-Stat3, p-Akt, and p-NF-κB. Doxorubicin and cucurbitacin D affected the viability of MCF7, MDA-MB-231, and SKBR3 cells. Cucurbitacin D and doxorubicin increased p-p53 expression in MCF7, SKBR3, and MDA-MB-231 cells. Cucurbitacin D suppressed p-Akt, p-NF-κB, and p-Stat3 expression in MCF7, MDA-MB-231, and SKBR3 cells. Doxorubicin alone did not decrease p-Akt and p-Stat3 levels. Cucurbitacin D decreased p-NF-κB and p-Stat3 levels. Doxorubicin in combination with cucurbitacin D increased p-p53 levels and suppressed Akt, NF-κB, Stat3, and Bcl-2 expression more than cucurbitacin D alone. Our results clearly demonstrate that cucurbitacin D could be a useful compound for treating human breast cancer.

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“…However, Dox induces nuclear factor-κB (NF-κB) activation which is believed to contribute to the development of chemoresistance [56]; thus, a viable option in cancer therapy could be the inhibition of NF-κB activation to overcome the chemoresistance. Among various biological systems exploited to obtain therapeutic benefits, the ubiquitin-proteasome system has been associated with tumor cell survival [57].…”

Section: Combined Therapy With Proteasome Inhibitormentioning

confidence: 99%

Epigenetic Approaches in Neuroblastoma Disease Pathogenesis

Caputi¹,

Candeletti²,

Romualdi³

2017

Neuroblastoma - Current State and Recent Updates

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Neuroblastoma is an embryonal extracranial solid tumor originating from undifferentiated neural crest cell and it is the most common among children. Neuroblastoma is highly heterogeneous, and on these bases different outcomes are observed across the subtypes. Its clinical impact (~13% of all pediatric cancer mortality) has made this aggressive malignancy the focus of a considerable translational research effort. New insights into tumor biology are leading to the development of novel therapeutic approaches, which include small-molecule inhibitors as well as epigenetic approaches, noncoding-RNA, and cell-based immunologic therapies. Recently, chromatin immunoprecipitation with high-throughput sequencing and RNA-sequencing studies have demonstrated that epigenetic changes contribute to the aggressive pathophysiology of pediatric neuroblastoma disease. Epigenetic abnormalities are feature of human cancer cells and the epigenetic alterations may be the key toward tumorigenesis. In particular, the increase of deacetylation has been involved in epigenetically mediated tumor-suppressor gene silencing. In addition, several studies evaluated the 5-methylcytosine (5 mC) distribution patterns, which distinguish cancer cells from normal cells, and how CpG methylation contributes to the oncogenic phenotype.In particular, histone changes and DNA methylation are fundamental biological processes representing versatile candidates for pharmacological manipulation with important therapeutic advantages.

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Cucurbitacin D induces cell cycle arrest and apoptosis by inhibiting STAT3 and NF-κB signaling in doxorubicin-resistant human breast carcinoma (MCF7/ADR) cells

Cited by 67 publications

References 29 publications

Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer

Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer

Cucurbitacin D exhibits its anti-cancer effect in human breast cancer cells by inhibiting Stat3 and Akt signaling

Epigenetic Approaches in Neuroblastoma Disease Pathogenesis

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