scholarly journals Evodiamine Eliminates Colon Cancer Stem Cells via Suppressing Notch and Wnt Signaling

Molecules ◽  
2019 ◽  
Vol 24 (24) ◽  
pp. 4520 ◽  
Author(s):  
Hyejin Kim ◽  
Yeongji Yu ◽  
SeokGyeong Choi ◽  
Hani Lee ◽  
Jinsuh Yu ◽  
...  

Evodiamine, an alkaloid contained in traditional Asian herbal medicines that have been used for hundreds years, is interesting due to its cytotoxic effects against many cancers. We examined the effect of evodiamine on the cancer stem cell (CSC) population and the bulk cultured cancer cells (BCC) of colon cancers to examine the double targeting effect. We found that three colon cancer cell lines’ BCC and CSC are effectively targeted by evodiamine. Evodiamine was able to suppress BCC proliferation and induce apoptosis of the cells captured in G2/M phase, as previously reported. However, evodiamine did not cause the accumulation of CSCs at a certain stage of the cell cycle, resulting in the elimination of stemness through an unknown mechanism. By analyzing the expression of 84 genes related to CSCs in two colon cancer cell lines’ CSC, as well as performing further informatics analyses, and quantitative RT-PCR analyses of 24 CSC genes, we found that evodiamine suppressed the expression of the genes that control key signaling pathways of CSC, namely, WNT and NOTCH signaling, to lead CSC elimination. These results suggest that evodiamine should be further developed for targeting both BCCs and CSCs in colon cancers.

2019 ◽  
Vol 69 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Martin Ambrož ◽  
Markéta Šmatová ◽  
Michaela Šadibolová ◽  
Eva Pospíšilová ◽  
Pavlína Hadravská ◽  
...  

Abstract The present study is designed to find out if sesquiterpenes, α-humulene (HUM), valencene (VAL), β-caryphyllene-oxide (CAO) and trans-nerolidol (NER), are able to improve the antiproliferative effect of classical cytostatic drugs, 5-fluorouracil (FU) and oxaliplatin (1,2-diaminocyclohexaneoxalato-platinum, OxPt), in colon cancer cell lines Caco-2 and SW-620. In addition, the possible mechanisms of sesquiterpene action are studied. The results show significant ability of HUM and especially of CAO to enhance the anti-proliferative effects of FU and OxPt in cancer cell lines Caco-2 and SW-620. On the other hand, VAL and NER are ineffective. The action of CAO could be partly based on its ability to disrupt the mitochondrial membrane potential and to activate initiator caspases, but other mechanisms are probably also involved. Based on these results, CAO seems to have the potential for combination therapy of colon cancers and deserves further study.


2019 ◽  
Vol 9 (4) ◽  
pp. 341-348 ◽  
Author(s):  
Ibrahim Awad Mohammed ◽  
Muhammad Nadeem Akhtar ◽  
Foo Jhi Biau ◽  
Yin Sim Tor ◽  
Seema Zareen ◽  
...  

<P>Background: Breast cancer and human colon cancer are the most common types of cancer in females and males, respectively. Breast cancer is the most common type of cancer after lung and colon cancers. Natural products are an important source for drug discovery. Boesenbergia rotunda (L.) Mansf. is commonly known as finger root, belonging to the Zingiberaceae family. </P><P> Objective: The aim of this study to isolate some natural compounds from the rhizomes of B. rotunda (L.) Mansf., and to investigate their cytotoxicity against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. </P><P> Methods: The dried rhizomes of B. rotunda were extracted with methanol. The methanolic extract was further used for solvent-solvent extraction. Bioassay-guided extraction and isolation of the rhizomes of the B. rotunda exhibited cytotoxic properties of hexane and dichloromethane fractions. </P><P> Results: Six major chemical constituents, pinostrobin (1), pinostrobin chalcone (2), cardamonin (3), 4,5-dihydrokawain (4), pinocembrin (5), and alpinetin (6) were isolated from the rhizomes of the B. rotunda. All the chemical constituents were screened against the human triple-negative breast cancer cell (MDA-MB-231) and HT-29 colon cancer cell lines. The compound cardamonin (3) (IC50 = 5.62&#177;0.61 and 4.44&#177;0.66 &#181;g/mL) and pinostrobin chalcone (2), (IC50 = 20.42&#177;2.23 and 22.51&#177;0.42 μg/mL) were found to be potent natural cytotoxic compounds against MDA-MB-231 and HT-29 colon cancer cell lines, respectively. </P><P> Conclusion: Cardamonin (3) and pinostrobin chalcone (2) were found to be the most potential natural compounds against breast cancer cell line MDA-MB-231 and colon cancer HT-29 cell line.</P>


1993 ◽  
Vol 11 (5-6) ◽  
pp. 225-237
Author(s):  
Udo Schumacher ◽  
Dhia Mukthar ◽  
Thomas Schenker

A panel of monoclonal antibodies (n=72 including controls) directed against lung cancer antigens was screened immunohistochemically against a panel of seven human lung cancer cell lines (including small cell carcinoma, squamous cell carcinoma, adenocarcinoma and mesothelioma), six human breast cancer cell lines and one human colon cancer cell line, The majority of the antibodies (n=42) reacted also with antigens present on breast and colon cancer cell lines, This cross reactivity especially between lung and breast cancer cell lines is not altogether unexpected since antigens common to breast and lung tissue including their neoplasms such as MUC1 antigen have been described, Our results indicate that epitopes shared by lung and breast cancers are probably more common than previously thought. The relevance for prognosis and therapy of these shared antigens, especially as disease markers in breast cancer, has to be investigated.


RSC Advances ◽  
2018 ◽  
Vol 8 (29) ◽  
pp. 15973-15984 ◽  
Author(s):  
Saghya Infant Shofia ◽  
Kannan Jayakumar ◽  
Amitava Mukherjee ◽  
Natarajan Chandrasekaran

Bioactive polysaccharides extracted from brown seaweeds have potent antioxidant, antitumor, antibacterial, antiviral, anti-inflammatory activities and nanomedicine applications.


2016 ◽  
Vol 16 (4) ◽  
pp. 585-596 ◽  
Author(s):  
Ji-Ye Kee ◽  
Yo-Han Han ◽  
Jinbong Park ◽  
Dae-Seung Kim ◽  
Jeong-Geon Mun ◽  
...  

Background: β-Lapachone is a quinone-containing compound found in red lapacho ( Tabebuia impetiginosa, syn. T avellanedae) trees. Lapacho has been used in traditional medicine by several South and Central American indigenous people to treat various types of cancer. The purpose of this study was to investigate the antimetastatic properties of β-lapachone and the underlying mechanisms using colon cancer cells. Methods: This research used metastatic murine colon cancer cell lines, colon 26 (CT26) and colon 38 (MC38). A WST assay, annexin V assay, cell cycle analysis, wound healing assay, invasion assay, western blot analysis, and real-time reverse transcription–polymerase chain reaction were performed to examine the effects of β-lapachone on metastatic phenotypes and molecular mechanisms. The effect of β-lapachone on lung metastasis was assessed in a mouse experimental metastasis model. Results: We found that the inhibition of proliferation of the colon cancer cell lines by β-lapachone was due to the induction of apoptosis and cell cycle arrest. β-Lapachone induced the apoptosis of CT26 cells through caspase-3, -8, and -9 activation; poly(ADP-ribose) polymerase cleavage; and downregulation of the Bcl-2 family in a dose- and time-dependent manner. In addition, a low concentration of β-lapachone decreased the cell migration and invasion by decreasing the expression of matrix metalloproteinases-2 and -9, and increased the expression of tissue inhibitors of metalloproteinases-1 and -2. Moreover, β-lapachone treatment regulated the expression of epithelial-mesenchymal transition markers such as E- and N-cadherin, vimentin, β-catenin, and Snail in CT26 cells. In the mouse experimental metastasis model, β-lapachone significantly inhibited the lung metastasis of CT26 cells. Conclusions: Our results demonstrated the inhibitory effect of β-lapachone on colorectal lung metastasis. This compound may be useful for developing therapeutic agents to treat metastatic cancer.


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