Cytotoxic activity of 3,3′,4,4′,5,5′-hexahydroxystilbene against breast cancer cells is mediated by induction of p53 and downregulation of mitochondrial superoxide dismutase

Murias, Marek; Łuczak, Michał W.; Niepsuj, Anna; Krajka‐Kuźniak, Violetta; Zielińska-Przyjemska, Małgorzata; Jagodzińśki, Paweł P.; Jäger, Walter; Szekeres, Thomas; Jodynis‐Liebert, Jadwiga

doi:10.1016/j.tiv.2008.03.002

Cited by 42 publications

(36 citation statements)

References 48 publications

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“…Consistently, p53 was found to be activated and led to a transcription of a subset of apoptotic proteins and of cyclindependent kinase inhibitors interfering with the cell cycle. In line with our data, M8 has recently been shown to induce p53 in breast cancer cells (Murias et al, 2008). Moreover, M8 impaired cell migration by regulating the Rho pathway.…”

Section: Discussionsupporting

confidence: 91%

3,3′,4,4′,5,5′-Hexahydroxystilbene Impairs Melanoma Progression in a Metastatic Mouse Model

Paulitschke

Schicher

Szekeres

et al. 2010

Journal of Investigative Dermatology

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Stilbenes comprise a group of polyphenolic compounds, which exert inhibitory effects on various malignancies. The aim of this study was to evaluate the antitumor effects of a previously unreported stilbene derivative-3,3',4,4',5,5'-hexahydroxystilbene, termed M8-on human melanoma cells. Cell-cycle analysis of the metastatic melanoma cell line M24met showed that M8 treatment induces G(2)/M arrest accompanied with a dose- and time-dependent upregulation of p21 and downregulation of CDK-2 and leads to apoptosis. M8 induces the expression of phosphorylated p53, proteins involved in the mismatch repair machinery (MSH6, MSH2, and MLH1) and a robust tail moment in a comet assay. In addition, M8 inhibited cell migration in Matrigel assays. Shotgun proteomics and western analysis showed the regulation among others of paxillin, integrin-linked protein kinase, p21-activated kinase, and ROCK-1 indicating that M8 inhibits mesenchymal and amoeboid cell migration. These in vitro data were confirmed in vivo in a metastatic human melanoma severe combined immunodeficient (SCID) mouse model. We showed that M8 significantly impairs tumor growth. M8 also interfered with the metastatic process, as M8 treatment prevented the metastatic spread of melanoma cells to distant lymph nodes in vivo. In summary, M8 exerts strong antitumor effects with the potential to become a new drug for the treatment of metastatic melanoma.

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Section: Discussionsupporting

confidence: 91%

3,3′,4,4′,5,5′-Hexahydroxystilbene Impairs Melanoma Progression in a Metastatic Mouse Model

Paulitschke

Schicher

Szekeres

et al. 2010

Journal of Investigative Dermatology

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“…Frankincense essential oil may represent a candidate on a growing list of natural compounds selectively eradicating cancer cells via oxidative stress [57-59]. To our knowledge, this is the first report suggesting that the NRF2-mediated oxidative stress response pathway might be involved in the tumor cell-specific anti-proliferative and pro-apoptotic activities of frankincense essential oil.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of selective frankincense (Ru Xiang) essential oil versus non-selective sandalwood (Tan Xiang) essential oil on cultured bladder cancer cells: a microarray and bioinformatics study

Dozmorov

Yang

et al. 2014

Chin Med

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BackgroundFrankincense (Boswellia carterii, known as Ru Xiang in Chinese) and sandalwood (Santalum album, known as Tan Xiang in Chinese) are cancer preventive and therapeutic agents in Chinese medicine. Their biologically active ingredients are usually extracted from frankincense by hydrodistillation and sandalwood by distillation. This study aims to investigate the anti-proliferative and pro-apoptotic activities of frankincense and sandalwood essential oils in cultured human bladder cancer cells.MethodsThe effects of frankincense (1,400–600 dilutions) (v/v) and sandalwood (16,000–7,000 dilutions) (v/v) essential oils on cell viability were studied in established human bladder cancer J82 cells and immortalized normal human bladder urothelial UROtsa cells using a colorimetric XTT cell viability assay. Genes that responded to essential oil treatments in human bladder cancer J82 cells were identified using the Illumina Expression BeadChip platform and analyzed for enriched functions and pathways. The chemical compositions of the essential oils were determined by gas chromatography–mass spectrometry.ResultsHuman bladder cancer J82 cells were more sensitive to the pro-apoptotic effects of frankincense essential oil than the immortalized normal bladder UROtsa cells. In contrast, sandalwood essential oil exhibited a similar potency in suppressing the viability of both J82 and UROtsa cells. Although frankincense and sandalwood essential oils activated common pathways such as inflammatory interleukins (IL-6 signaling), each essential oil had a unique molecular action on the bladder cancer cells. Heat shock proteins and histone core proteins were activated by frankincense essential oil, whereas negative regulation of protein kinase activity and G protein-coupled receptors were activated by sandalwood essential oil treatment.ConclusionThe effects of frankincense and sandalwood essential oils on J82 cells and UROtsa cells involved different mechanisms leading to cancer cell death. While frankincense essential oil elicited selective cancer cell death via NRF-2-mediated oxidative stress, sandalwood essential oil induced non-selective cell death via DNA damage and cell cycle arrest.

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“…It must be stressed, however, that the dose of 10 μM is relatively low, especially in the context of multiple studies on malignant cells in which M8 inhibited cell growth and/or triggered apoptosis. For instance, the proliferation assays performed on various types of breast cancer cells treated with M8 revealed that IC 50 values for this stilbene range from 90 to 127 μM [12]. In studies on melanoma cells, IC 50 was between 20 and 25 μM [15].…”

Section: Discussionmentioning

confidence: 99%

“…These studies are based on a paradigm that an introduction of additional groups into the stilbene structure strengthens biological properties of RVT analogues [11]. Of these newly synthesized derivatives, high expectations are linked with 3,3′,4,4′,5,5′-hexahydroxy- trans -stilbene (M8) which has been found to inhibit growth and/or induce apoptosis in various malignancies, including breast and colon cancers [12,13], leukemia [14], melanoma [15], and glioma cells [16] (Figure 1). …”

Section: Introductionmentioning

confidence: 99%

Synthetic Resveratrol Analogue, 3,3',4,4',5,5'-Hexahydroxy-trans-Stilbene, Accelerates Senescence in Peritoneal Mesothelium and Promotes Senescence-Dependent Growth of Gastrointestinal Cancers

Mikuła-Pietrasik

Sosińska

Wierzchowski

et al. 2013

IJMS

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3,3′,4,4′,5,5′-Hexahydroxy-trans-stilbene (M8) is a synthetic resveratrol derivative, advertised as a candidate drug highly effective against numerous malignancies. Because multiple tumors prone to M8 frequently metastasize into the peritoneal cavity, this study was aimed at establishing the effect of M8 on the growth and senescence of human peritoneal mesothelial cells (HPMCs), the largest cell population within the peritoneum, actively involved in the intraperitoneal spread of cancer. The study showed that M8, used at the highest non-toxic dose of 10 μM, impairs proliferation and accelerates senescence in cultured HPMCs via an oxidative stress-dependent mechanism. At the same time, soluble factors released to the environment by HPMCs that senesced prematurely in response to M8 promoted growth of colorectal and pancreatic carcinomas in vitro. These findings indicate that M8 may indirectly—through the modification of normal (mesothelial) cells phenotype—facilitate an expansion of cancer cells, which challenges the postulated value of this stilbene in chemotherapy.

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Cytotoxic activity of 3,3′,4,4′,5,5′-hexahydroxystilbene against breast cancer cells is mediated by induction of p53 and downregulation of mitochondrial superoxide dismutase

Cited by 42 publications

References 48 publications

3,3′,4,4′,5,5′-Hexahydroxystilbene Impairs Melanoma Progression in a Metastatic Mouse Model

3,3′,4,4′,5,5′-Hexahydroxystilbene Impairs Melanoma Progression in a Metastatic Mouse Model

Differential effects of selective frankincense (Ru Xiang) essential oil versus non-selective sandalwood (Tan Xiang) essential oil on cultured bladder cancer cells: a microarray and bioinformatics study

Synthetic Resveratrol Analogue, 3,3',4,4',5,5'-Hexahydroxy-trans-Stilbene, Accelerates Senescence in Peritoneal Mesothelium and Promotes Senescence-Dependent Growth of Gastrointestinal Cancers

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