Platyphylloside Isolated from Betula platyphylla is Antiproliferative and Induces Apoptosis in Colon Cancer and Leukemic Cells

Betula platyphylla bark has been evaluated for the treatment of dermatitis, inflammatory conditions, and cancer. Diarylheptanoids are the major constituents of the B. platyphylla bark and possess various pharmacological effects. Our previous study confirmed the selective antiproliferative effect of platyphylloside (BPP) isolated from B. platyphylla on colon cancer and leukemic cells using 60 different cancer cell lines from thr National Cancer Institution (NCI). In line with previous reports, this study focuses on the apoptotic pathway of BPP, a phenolic glycoside composed of two aromatic rings joined by a seven-carbon chain. Cytotoxicity assays in solid tumor and blood cancer cell models demonstrated that BPP possesses potent antiproliferative activity. The level of apoptosis increased with BPP treatment, causing cell cycle arrest at the G1 phase along with the downregulation of IκBα phosphorylation and BCL-2, as well as upregulation of cleaved caspase 3 and BAX proteins. In addition, BPP displayed potent mitochondrial depolarization effects in Jurkat cells. The combined findings revealed that the cytotoxic effects of BPP were mediated by intracellular signaling, possibly through a mechanism involving the upregulation of mitochondrial reactive oxygen species (ROS). Thus, BPP could be a potential multitarget therapeutic agent in leukemia and colon cancer.

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An Antiproliferative ent-Kaurane Diterpene Isolated from the Roots of Mallotus japonicus Induced Apoptosis in Leukemic Cells

Natural Product Communications ◽

10.1177/1934578x19897496 ◽

2020 ◽

Vol 15 (1) ◽

pp. 1934578X1989749

Author(s):

Joo-Eun Lee ◽

Nguyen Thi Thanh Thuy ◽

Youngju Lee ◽

Namki Cho ◽

Hee Min Yoo

Keyword(s):

Intracellular Signaling ◽

Therapeutic Agent ◽

Jurkat Cells ◽

Leukemic Cells ◽

Mitochondrial Depolarization ◽

Cytotoxic Effects ◽

Inflammatory Conditions ◽

Cycle Arrest ◽

Mallotus Japonicus ◽

Induced Apoptosis

Mallotus japonicus has been evaluated for the treatment of dermatitis, inflammatory conditions, and cancer. Diterpenes, one of the major constituents of M. japonicus, possess various pharmacological effects. In this study, 2 known diterpenes, anomaluone (6) and 16-epiabbeokutone (7), along with other known compounds, 2-hydroxy ferulic acid (1), bergenin (2), gallocatechin (3), catechin (4), erythro,erythro-1-[4-[2-hydroxy-2-(4-hydroxy-3-methoxyphenyl)-1-(hydroxymethyl) ethoxy]-3,5-dimethoxyphenyl]-1,2,3- propanetriol (5), and gallincin (8), were isolated from M. japonicus. Cytotoxicity assays in blood cancer cell models demonstrated that M. japonicus compounds possess potent antiproliferative activity. In addition, treatment with compound 6 increased the number of apoptotic cells, led to cell-cycle arrest at the subG0/G1 phase, and decreased the number of cells in the S and G2/M phases. Compound 6 also displayed potent mitochondrial depolarization effects in Jurkat cells. These findings revealed that the cytotoxic effects of 6 were mediated by intracellular signaling, possibly through a mechanism involving upregulation of mitochondrial reactive oxygen species. Thus, compound 6 could be a potential multi-target therapeutic agent for leukemia.

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Evaluation of the Effects of the Flavonoid Apigenin on Apoptotic Pathway Gene Expression on the Colon Cancer Cell Line (HT29)

Journal of Medicinal Food ◽

10.1089/jmf.2010.0208 ◽

2011 ◽

Vol 14 (10) ◽

pp. 1107-1117 ◽

Cited By ~ 38

Author(s):

Mehmet Turktekin ◽

Ece Konac ◽

H. Ilke Onen ◽

Ebru Alp ◽

Akin Yilmaz ◽

...

Keyword(s):

Gene Expression ◽

Colon Cancer ◽

Cell Line ◽

Cancer Cell ◽

Cancer Cell Line ◽

Colon Cancer Cell Line ◽

Colon Cancer Cell ◽

Apoptotic Pathway ◽

Pathway Gene

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Synthesis of 3-Trifluoromethyl-5,6-dihydro-[1,2,4]triazolo Pyrazine Derivatives and Their Anti-Cancer Studies

Molbank ◽

10.3390/m1173 ◽

2020 ◽

Vol 2020 (4) ◽

pp. M1173

Author(s):

Rajaiah Raveesha ◽

Malavalli Guruswamy Dileep Kumar ◽

Salekoppal Boregowda Benaka Prasad

Keyword(s):

Colon Cancer ◽

Cell Lines ◽

Cancer Cell ◽

Cancer Cell Lines ◽

Colon Cancer Cell ◽

Apoptotic Pathway ◽

Mitochondrial Apoptotic Pathway ◽

Colon Cancer Cell Lines ◽

Anti Cancer ◽

Ht 29

The synthesis of a wide variety of 3-trifluoromethyl-5,6-dihydro-[1,2,4]triazolo pyrazine derivatives, by the treatment of 3-trifluoromethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-α]pyrazine hydrochloride with an array of isocyanates in the presence of triethylamine, is reported. All the target compounds were synthesized in excellent yields under mild reaction conditions. The target molecules were effectively screened for their anti-cancer properties and the results are promising. The resultant compounds were assessed for their antiproliferative action against two human colon cancer cell lines (HCT-116 and HT-29 colon cancer cell lines). The IC50 range was estimated at 6.587 to 11.10 µM showing that compound RB7 had remarkable anticancer movement on HT-29. Additionally, it was discovered that RB7 incited the mitochondrial apoptotic pathway by up-regulating Bax and down-regulating Bcl2, eventually leading to the activation of Caspase 3 in HT-29 cells and initiation of cell death via the mitochondrial apoptotic pathway.

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Inhibition of Colon Cancer Cell Growth by Imidazole Through Activation of Apoptotic Pathway

Medical Science Monitor ◽

10.12659/msm.917779 ◽

2019 ◽

Vol 25 ◽

pp. 7597-7604

Author(s):

Yaxin Long ◽

Duo Wang

Keyword(s):

Colon Cancer ◽

Cell Growth ◽

Cancer Cell ◽

Colon Cancer Cell ◽

Cancer Cell Growth ◽

Apoptotic Pathway

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SK1 inhibitor RB005 Induces Apoptosis in Colorectal Cancer Cells through SK1 Inhibition Dependent and Independent Pathway

Current Molecular Pharmacology ◽

10.2174/1874467214666210811151324 ◽

2021 ◽

Vol 14 ◽

Author(s):

Jitendra Shrestha ◽

Maftuna Shamshiddinova ◽

Yong-Moon Lee ◽

Yoon-Sin Oh ◽

Dong Jae Baek ◽

...

Keyword(s):

Colorectal Cancer ◽

Colon Cancer ◽

Cell Death ◽

Cancer Cells ◽

Cancer Cell ◽

Apoptotic Cell ◽

Colon Cancer Cell ◽

Lipid Mediator ◽

Intrinsic Apoptotic Pathway ◽

Apoptotic Pathway

Background and Objective: Colorectal cancer (CRC) is the fourth leading cause of cancer-related death globally, with a high incidence rate in economically fast-growing countries. Sphingosine-1-phosphate (S1P) is a bioactive lipid mediator that plays critical roles in cancer cell proliferation, migration, and angiogenesis converted by the isoforms of sphingosine kinase (SK1 and SK2). SK1 is highly expressed in colorectal cancer, its inhibitors suppress the formation of S1P and increase ceramide levels having a pro-apoptotic function. RB005 is a selective SK1 inhibitor and a structural analog of PP2A activator FTY720. The purpose of this study is to test whether RB005, an SK1 inhibitor, can be used as an anticancer agent by inhibiting the growth of colon cancer cells. Methods: We performed MTT and colony-forming assay using colon cancer cell lines HT29 and HCT116 cells to examine the cell toxicity effect of RB005. To determine whether apoptosis of RB005 in colon cancer cell line is due to SK1 inhibition or other mechanisms due to its structural similarity with FTY720, we conducted LC/MS, siRNA knockdown, and PP2A activity experiments. Results: RB005 notably inhibited CRC cell growth and proliferation compared to PF543 and ABC294640 by inducing the mitochondria-mediated intrinsic apoptotic pathway. Apoptotic cell death is caused by increased mitochondrial permeability necessitated by the activation of pro-apoptotic protein BAX, increased ceramides, and activation of PP2A. Also, RB005 treatment in HT29 cells did not change the expression level of SK1, but strikingly decreased SK1 activity and S1P levels. All these events of cell death and apoptosis were less effective when SK1 was knocked down by siRNA. Conclusion: This result indicates that RB005 shows the in-vitro anti-CRC effect by inhibiting SK1 activity and PP2A activation, increasing proapoptotic ceramide levels following the activation of the intrinsic apoptotic pathway.

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Effects of As2O3 and Resveratrol on the Proliferation and Apoptosis of Colon Cancer Cells and the hERG-mediated Potential Mechanisms

Current Pharmaceutical Design ◽

10.2174/1381612817666190619123610 ◽

2019 ◽

Vol 25 (12) ◽

pp. 1385-1391 ◽

Cited By ~ 1

Author(s):

Caichuan Yan ◽

Fengmei Li ◽

Yuhao Zhang ◽

Yang Li ◽

Mingzhu Li ◽

...

Keyword(s):

Colon Cancer ◽

Cancer Cells ◽

Intracellular Signaling ◽

Combined Treatment ◽

Human Colon ◽

Cancer Therapies ◽

Colon Cancer Cells ◽

Human Colon Cancer ◽

Apoptotic Pathway ◽

Underlying Mechanisms

Background: As2O3 and resveratrol have been widely considered to be effective in anti-cancer therapies and the underlying mechanisms have been reported extensively. However, the combined treatment effect and potential target of As2O3 and resveratrol in the treatment of tumors remains elusive. The purpose of this study was to investigate the benefits and efficacy of As2O3 in combination with resveratrol in the treatment of colon cancer, as well as looking for new targets that could provide alternative explanation of the efficacy of drugs. Methods: The proliferation of cancer cells was measured by the MTT and EdU staining assay, while the apoptosis of cancer cells was determined by the flow cytometry. Western blot and immunoprecipitation were performed to measure the expression levels of proteins and the interaction between hERG and integrin β1, respectively. Results: In this study, we found that both As2O3 and resveratrol can effectively inhibit cell proliferation and promote cell apoptosis in colon cancer, and the combined effect of the two drugs on colon cancer cells is more preeminent. The combination of As2O3 with resveratrol, on the one hand reduced the expression of hERG channels on the membrane, and on the other hand weaken the binding between hERG and integrin β 1, which may be the main cause of downstream signaling pathways alterations, including the activation of the apoptotic pathway. Conclusion: Taken together, hERG, as a subunit of potassium ion channel on the cell membrane, is highly likely to be involved in the As2O3 and resveratrol induced intracellular signaling cascade disorder, and this novel signaling pathway that sustains the progression of colon cancer may be a promising therapeutic target for human colon cancer treatment in the future.

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