Delphinidin induces cytotoxicity and potentiates cytocidal effect in combination with arsenite in an acute promyelocytic leukemia NB4 cell line

Yuan, Bo; Okusumi, Saki; Yoshino, Yuta; Moriyama, Chihiro; Tanaka, Sachiko; Hirano, Toshihiko; Takagi, Norio; Toyoda, Hiroo

doi:10.3892/or.2015.3963

Cited by 20 publications

(21 citation statements)

References 36 publications

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“…Similarly, cyanidin-3-rutinoside was also shown to generate ROS in leukemia cells to cause cytostatics effects [27]. Therefore, combining these agents with other drugs that act in a ROS-dependent or independent manner is suggested to potentiate the action that contributes to cancer cell killing [28,29]. Proanthocyanidins on the other hand were shown to enhance the doxorubicin (DOX)-induced anti-tumor effects and reverse drug resistance thus enhancing anti-cancer effects [30,31].…”

Section: Resultsmentioning

confidence: 99%

Lung cancer inhibitory activity of dietary berries and berry polyphenolics

Aqil

Jeyabalan

Kausar

et al. 2016

JBR

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Abstract.BACKGROUND: Blueberry (BB) and black raspberry (BRB) have been shown to be chemopreventive against estrogenmediated breast cancer in pre-clinical studies. However, therapeutic efficacy of these berries against lung cancer is not known. METHODS: In this study we investigated i) relative efficacy of individual anthocyanidins vs. respective anthocyanins, ii) relative antiproliferative activity of mixture of anthocyanidins compared to individual anthocyanidins, iii) antitumor activity of dietary BB, iv) Tumor inhibitory activity of diet supplemented with BB, alone and in combination with BRB, against lung tumor xenograft using nude mice, and finally, v) the efficacy of select polyphenolics present in BB and BRB against lung tumor xenograft. RESULTS: Our findings indicated that individual anthocyanidins (aglycones) were significantly more potent (2-3 fold lower IC 50 ) in inhibiting the non-small-cell lung cancer (NSCLC) cell growth vs. respective anthocyanins (glycones). Further, anthocyanidins mixture at equimolar concentrations exhibited synergistic antiproliferative activity vs. individual anthocyanidins. When tested against NSCLC (A549 and H1299) cells in nude mice, dietary BB (7.5%, w/w) showed >40% reduction in tumor volume against H1299 xenografts. The maximal growth inhibition occurred with 5% BB dose, with no additional protection occurring at a higher dose (7.5%). However, somewhat lower protection was found when the BB diet initiated prior to tumor cell inoculation. The mixture of BB (5%, w/w) and BRB (2.5%) resulted in higher inhibition of tumor growth vs. BB alone (71% vs 42%). Likewise, a combination of delphinidin (bioactive of BB) and punicalagins (a bioactive of BRB, which gets converted to ellagic acid in vivo) showed higher tumor growth inhibition compared to delphinidin. CONCLUSIONS: The therapeutic effects of the berries and berry polyphenolics observed against lung cancer in this study are highly encouraging. Further investigation into the mechanism of action of the combinations of the berry bioactives will be valuable for clinical use of this potent natural product against lung cancer.

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Section: Resultsmentioning

confidence: 99%

Lung cancer inhibitory activity of dietary berries and berry polyphenolics

Aqil

Jeyabalan

Kausar

et al. 2016

JBR

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“…Collectively, the combination regimen of Tetra and As III may be expected not only to achieve improved efficacy of As III , but also overcome its adverse cardiac effects secondary to Tetra functioning as calcium channel blocker (44). Cell cycle arrest, necrosis, as well as autophagic cell death have all been viewed as the major underlying mechanisms for the cytocidal effects of most drugs used against tumors (7,13,(15)(16)(17)(18). To examine the probable mechanisms underlying the cytocidal effect of the combination of As III and Tetra, cell cycle arrest was first examined in MCF-7 cells treated with As III and Tetra, alone or in combination.…”

Section: Discussionmentioning

confidence: 99%

“…The As[i] was normalized by the amount of proteins and reported as parts per billion (ppb) of arsenic per mg of proteins. The analysis of total arsenic was performed by inductively coupled plasma-mass spectrometry (ICP-MS) (Perkin-Elmer Sciex, Thornhill, ON, Canada) according to the methods previously reported (17,33,41).…”

Section: Analysis Of Intracellular Arsenic Accumulation (As[i]mentioning

confidence: 99%

“…Cell cycle arrest, necrosis, as well as autophagic cell death have been viewed as the major underlying mechanisms for the cytocidal effects of most chemotherapeutic drugs (7,13,(15)(16)(17)(18). The cell cycle is a complex process that is precisely regulated by vital molecules known as cyclin-dependent kinases (CDKs) and CDK inhibitors such as p21 Waf1/Cip1 (p21) and p27 Kip1 (p27) (7,19,20).…”

Section: Introductionmentioning

confidence: 99%

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Synergistic cytotoxic effects of arsenite and tetrandrine in human breast cancer cell line MCF-7

Yao

Yuan

Wang

et al. 2017

International Journal of Oncology

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To provide novel insight into the development of new therapeutic strategies to combat breast cancer using trivalent arsenic (AsIII)-based combination therapy, the cytotoxicity of a combination of AsIII and tetrandrine (Tetra), a Chinese plant-derived alkaloid, was investigated in the human breast cancer cell line MCF-7. Cytotoxicity was evaluated using cell viability, colony formation, wound healing, lactate dehydrogenase leakage and cell cycle assay. Alterations of genes associated with cell proliferation and death were analyzed using real-time PCR and western blotting. Intracellular arsenic accumulation (As[i]) was also determined. Tetra significantly enhanced the cytotoxicity of AsIII in MCF-7 cells in a synergistic manner. The combined treatment upregulated the expression level of FOXO3a, and subsequently resulted in a concomitant increase in the expression levels of p21, p27, and decrease of cycline D1, which occurred in parallel with G0/G1 phase arrest. Autophagy induction was also observed in the combination treatment. Importantly, combining AsIII with Tetra exhibited a synergistic inhibitory effect on the expression level of survivin. Furthermore, enhanced As[i] along with synergistic cytotoxicity was observed in MCF-7 cells treated with AsIII combined with Tetra or Ko134, an inhibitor of breast cancer resistance protein (BCRP), suggesting that Tetra or the BCRP inhibitor probably intervened in the occurrence of resistance to arsenic therapy by enhancing the As[i] via modulation of multidrug efflux transporters. These results may provide a rational molecular basis for the combination regimen of AsIII plus Tetra, facilitating the development of AsIII-based anticancer strategies and combination therapies for patients with solid tumors, especially breast cancer.

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“…As a representative of the flavonoid polyphenolic substances, delphinidin is widely found in plant-based food (10). It has powerful antibiosis, anti-inflammatory, anti-allergenic and anti-oxygenation activities (11).…”

Section: Introductionmentioning

confidence: 99%

Anti‑inflammatory effect of delphinidin on intramedullary spinal pressure in a spinal cord injury rat model

Wang

Zhu

et al. 2017

Exp Ther Med

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Abstract. Delphinidin, a flavonoid polyphenolic compound, is widely found in nature and is used as a food supplement due to its pharmacological activity. The aims of the present study were to examine the anti-inflammatory effect of delphinidin in alleviating spinal cord injury (SCI)-induced inflammation in a rat model and to determine the underlying mechanisms in SCI. The Basso, Beattie, Bresnahan (BBB) scores of rats were assessed to evaluate the effect of delphinidin on the recovery of motor function. ELISA kits were also used to analyze the activities of tumor necrosis factor-α (TNF-α), interleukin (IL)-6, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) and caspase-3. In addition, the protein expression levels of nuclear factor (NF)-κB, activator protein 1 (AP-1) and p38-MAPK protein expression were measured using western blot analysis. Treatment with delphinidin significantly increased the BBB scores, as well as inhibited the intramedullary spinal pressure in SCI rats. Delphinidin treatment also significantly suppressed the levels of inflammatory factors and NF-κB protein expression in SCI rats. Finally, treatment with delphinidin significantly inhibited NF-κB stimulation, COX-2 activity, PGE2 production, and AP-1 and p38-MAPK protein expression in SCI rats. These results suggest that the anti-inflammatory effect of delphinidin alleviated inflammation in the SCI rat model via alleviation of the intramedullary spinal pressure through the NF-κB and p38-MAPK signaling pathways.

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Delphinidin induces cytotoxicity and potentiates cytocidal effect in combination with arsenite in an acute promyelocytic leukemia NB4 cell line

Cited by 20 publications

References 36 publications

Lung cancer inhibitory activity of dietary berries and berry polyphenolics

Lung cancer inhibitory activity of dietary berries and berry polyphenolics

Synergistic cytotoxic effects of arsenite and tetrandrine in human breast cancer cell line MCF-7

Anti‑inflammatory effect of delphinidin on intramedullary spinal pressure in a spinal cord injury rat model

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