Novel β-carbolines against colorectal cancer cell growth via inhibition of Wnt/β-catenin signaling

Li, X; Bai, Bing; Liu, L; Ma, Ping; Kong, Lingmei; Yan, Juming; Zhang, Jiaolong; Ye, Zhen-Nan; Zhou, Hu; Mao, Bingyu; Zhu, Huarui; Li, Y

doi:10.1038/cddiscovery.2015.33

Cited by 22 publications

(22 citation statements)

References 45 publications

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“…Inhibited Wnt/β‐catenin signaling pathway represses subcutaneous tumor growth, angiogenesis, and in vivo metastasis. Wnt signaling pathway is aberrantly activated in multiple cancers, including CRC, due to mutations in the genes encoding adenomatous polyposis coli, β‐catenin, and Axin . In CRC cells, significant inhibition of cell clonogenicity is associated with downregulation of intracellular β‐catenin protein level and β‐catenin activity .…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β‐catenin signaling pathway

Song

Shu

Zhang

et al. 2019

J of Cellular Biochemistry

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Objective Angiogenesis plays a key role in the tumorigenesis and progression of colorectal cancer (CRC). In this study, we investigated the effect of long noncoding RNA (lncRNA) GAS5 on the angiogenesis, invasion, and metastasis of CRC, and the involvement of the Wnt/β‐catenin signaling pathway. Methods CRC tissues and adjacent normal tissues were collected from 52 patients with CRC. GAS5 expression was determined in vivo and in vitro by real‐time quantitative polymerase chain reaction (RT‐qPCR). Then RT‐qPCR and Western blot were used to identify expression of key genes of Wnt/β‐catenin signaling pathway. CRC cells with lowest GAS5 expression were selected and subjected to si‐GAS5, oe‐GAS5, or XAV939 to validate the effect of GAS5 and Wnt/β‐catenin signaling pathway on CRC cell activities. The activation of Wnt/β‐catenin signaling pathway was determined in response to GAS5. Subcutaneous tumor growth and microvascular density were observed in nude mice, in which in vivo metastasis was observed following tail vein injection of CRC cells. Results Initially, poor expression of GAS5 was observed in CRC tissues and cells. Upregulated GAS5 repressed CRC cell invasion and migration in vitro, as well as subcutaneous tumor growth, angiogenesis, and liver metastases in vivo. Furthermore, the Wnt/β‐catenin signaling pathway was determined to be activated in CRC tissues and cells, while its activation was inhibited by GAS5. The Wnt/β‐catenin signaling pathway promoted the CRC cell invasion and migration in vitro, subcutaneous tumor growth, angiogenesis and, liver metastases in vivo. Conclusion Taken together, the results of the study conclude that lncRNA GAS5 inhibited the activation of the Wnt/β‐catenin signaling pathway, thereby suppressing the angiogenesis, invasion, and metastasis of CRC.

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Section: Discussionmentioning

confidence: 99%

Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β‐catenin signaling pathway

Song

Shu

Zhang

et al. 2019

J of Cellular Biochemistry

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“…This section mainly focused on the in vitro cytotoxicity of harmaline in human cervical and hepatic cancer cell lines, thereby inducing apoptosis by harmaline. Earlier, β‐carboline alkaloids and its various derivatives have also been reported to show in vitro cytotoxicity in many cancer cell lines . Harmaline, a dihydro‐β‐carboline moiety, being one of the important members from this group, was also reported to show cytotoxicity, but a lacuna lies in its complete detailed study of apoptosis induction ability.…”

Section: Resultsmentioning

confidence: 99%

“…Earlier, β-carboline alkaloids and its various derivatives have also been reported to show in vitro cytotoxicity in many cancer cell lines. [72][73][74][75][76][77][78] Harmaline, a dihydro-β-carboline moiety, being one of the important members from this group, was also reported to show cytotoxicity, 79 Figure 8A). We further characterized the apoptotic HepG 2 cells by the formation of comet tails ( Figure 8B).…”

Section: In Vitro Cytotoxicity Of Harmalinementioning

confidence: 99%

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

Bhattacharjee

Ghosh

Sarkar

et al. 2017

J of Molecular Recognition

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The work focuses towards interaction of harmaline, with nucleic acids of different motifs by multispectroscopic and calorimetric techniques. Findings of this study suggest that binding constant varied in the order single-stranded (ss) poly(A) > double-stranded calf thymus (CT) DNA > double-stranded poly(G)·poly(C) > clover leaf tRNA . Prominent structural changes of ss poly(A), CT DNA, and poly(G)· poly(C) with concomitant induction of optical activity in the bound achiral alkaloid molecule was observed, while with tRNA , very weak induced circular dichroism perturbation was seen. The interaction was predominantly exothermic, enthalpy driven, and entropy favored with CT DNA and poly(G)·poly(C), while it was entropy driven with poly(A) and tRNA . Intercalated state of harmaline inside poly(A), CT DNA, and poly(G)·poly(C) was shown by viscometry, ferrocyanide quenching, and molecular docking. All these findings unequivocally pointed out preference of harmaline towards ss poly(A) inducing self-structure formation. Furthermore, harmaline administration caused a significant decrease in proliferation of HeLa and HepG cells with GI of 28μM and 11.2μM, respectively. Nucleic acid fragmentation, cellular ultramorphological changes, decreased mitochondrial membrane potential, upregulation of p53 and caspase 3, generation of reactive oxygen species, and a significant increase in the G /M population made HepG more prone to apoptosis than are HeLa cells.

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“…Z86 suppressed the Wnt signaling functions and genes expression in mammalian cells. It suppressed the GSK3β (Ser9) phosphorylation, causing its overactivity and elevating the phosphorylation and β-catenin degradation[ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Novel targeting approaches and signaling pathways of colorectal cancer: An insight

Tiwari

Saraf

Verma

et al. 2018

WJG

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Colorectal cancer (CRC) is the third most common cancer of mortality in the world. Chemotherapy based treatment leads to innumerable side effects as it delivers the anticancer drug to both normal cells besides cancer cells. Sonic Hedgehog (SHH), Wnt wingless-type mouse mammary tumor virus/β-catenin, transforming growth factor-β/SMAD, epidermal growth factor receptor and Notch are the main signaling pathways involved in the progression of CRC. Targeted therapies necessitate information regarding the particular aberrant pathways. Advancements in gene therapies have resulted in the recognition of novel therapeutic targets related with these signal-transduction cascades. CRC is a step-wise process where mutations occur over the time and activation of oncogenes and deactivation of tissue suppressor genes takes place. Genetic changes which are responsible for the induction of carcinogenesis include loss of heterozygosity in tumor suppressor genes such as adenomatous polyposis coli, mutation or deletion of genes like p53 and K-ras. Therefore, many gene-therapy approaches like gene correction, virus-directed enzyme-prodrug therapy, immunogenetic manipulation and virotherapy are currently being explored. Development of novel strategies for the safe and effective delivery of drugs to the cancerous site is the need of the hour. This editorial accentuates different novel strategies with emphasis on gene therapy and immunotherapy for the management of CRC.

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Novel β-carbolines against colorectal cancer cell growth via inhibition of Wnt/β-catenin signaling

Cited by 22 publications

References 45 publications

Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β‐catenin signaling pathway

Long noncoding RNA GAS5 inhibits angiogenesis and metastasis of colorectal cancer through the Wnt/β‐catenin signaling pathway

Binding affinity and in vitro cytotoxicity of harmaline targeting different motifs of nucleic acids: An ultimate drug designing approach

Novel targeting approaches and signaling pathways of colorectal cancer: An insight

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