Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway

Foo, Jhi Biau; Yazan, Latifah Saiful; Tor, Yin Sim; Wibowo, Agustono; Ismail, Norsharina; How, Chee Wun; Armania, Nurdin; Loh, Su Peng; Ismail, Intan Safinar; Cheah, Yoke Kqueen; Abdullah, Rasedee

doi:10.1016/j.jep.2015.03.039

Cited by 52 publications

(41 citation statements)

References 51 publications

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“…Fluoroquinolones were reported to have the ability to penetrate pancreatic tissue, and are usually associated with loss or downregulation of the CDK inhibitors p21/p27 as well as with the mutational inactivation of p53 (26). Significantly upregulated p21 at both the gene and protein levels was found in MCF-7 cells treated with Dillenia suffruticosa root dichloromethane extract, and the results suggested that the induction of G0/G1-phase cell cycle arrest in MCF-7 cells was achieved via the p53/p21 pathway (21). In human lung adenocarcinoma cells, it was found that the upregulation of the lncRNA HOTAIR contributes to cisplatin resistance, at least in part, through the regulation of p21 expression (30).…”

Section: Discussionmentioning

confidence: 99%

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

et al. 2016

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Cisplatin has been used effectively in the treatment of hepatocellular carcinoma (HCC). Long noncoding RNAs (lncRNAs) were recently reported to contribute to the pathogenesis and progression of HCC. Their molecular mechanism related to cisplatin treatment remains unclear. The purpose of this study is to identify specific lncRNAs and to clarify their functions in HCC after cisplatin exposure. Reannotation and identification of differentially expressed lncRNAs were performed using the microarray data set GSE38122 in the Gene Expression Omnibus database. Four significantly differentially expressed lncRNAs (RP11-134G8.8, RP11-612B6.2, RP11-363E7.4 and RP1-193H18.2) were identified in HepG2 cells exposed to cisplatin by bioinformatics methods. The upregulated RP11-134G8.8 and RP11-363E7.4 and the downregulated RP1-193H18.2 were confirmed by reverse transcription-quantitative polymerase chain reaction. Furthermore, 57 significant co-expressing genes and their corresponding pathways were annotated and identified. The p53 signaling pathway showed the most significant difference among all pathways. Based on these results, the cell cycle and three key genes, cyclin-dependent kinase inhibitor 1A (CDKN1A, also known as p21), tumor protein p53 inducible protein 3 (TP53I3) and wild-type p53-induced phosphatase 1 (Wip1, also known as PPM1D), were examined. CDKN1A, TP53I3 and PPM1D were all downregulated by RP1-193H18.2 but upregulated by RP11-134G8.8 and RP11-363E7.4. And obvious S phase arrest was induced by cisplatin treatment for 24 h in HepG2 cells. Finally, the immunofluorescence results showed upregulation of TP53I3 and Wip1 and downregulation of p21 at the protein level. The results suggested that the lncRNAs RP11-134G8.8, RP11-363E7.4 and RP1-193H18.2, and their co-expression genes, which annotated into the p53 signaling pathway, could be potential targets for cisplatin treatment.

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Section: Discussionmentioning

confidence: 99%

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

et al. 2016

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“…Besides the above mechanisms of action, BetA also acts in a cell-specific manner (88,(122)(123)(124). It is well known that NF-jB plays a major role in stress-induced transcriptional activation.…”

Section: Effects On Other Molecular Targetsmentioning

confidence: 99%

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

et al. 2015

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An important method of drug discovery is examination of diverse life forms, including medicinal plants and natural products or bioactive compounds isolated from these sources. In cancer research, lead structures of compounds from natural sources can be used to design novel chemotherapies with enhanced biological properties. Betulinic acid (3β-hydroxy-lup-20(29)-en-28-oic acid or BetA) is a naturally occurring pentacyclic triterpene with a wide variety of biological activities, including potent antitumor properties. Non-malignant cells and normal tissues are not affected by BetA. Because BetA exerts its effects directly on the mitochondrion and triggers death of cancerous cells, it is an important alternative when certain chemotherapy drugs fail. Mitochondrion-targeted agents such as BetA hold great promise to circumvent drug resistance in human cancers. BetA is being developed by a large network of clinical trial groups with the support of the U.S. National Cancer Institute. This article discusses recent advances in research into anticancer activity of BetA, relevant modes of delivery, and the agent's therapeutic efficacy, mechanism of action, and future perspective as a pipeline anticancer drug. BetA is a potentially important agent in cancer therapeutics.

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“…In contrast to the conventional cancer chemotherapy agents targeting single molecule, the mixture of phytochemicals is able to target multiple-molecules involved in the same pathway or several pathways responsible for cancer development, and exerts better therapeutic efficacy and lower side effects1. Dried 4- to 5-year-old roots of Saussurea lappa , known as Mu-xiang, are commonly used as medicine to treat breast cancer and breast hyperplasia in China, Japan and India2.…”

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confidence: 99%

Costunolide and dehydrocostuslactone combination treatment inhibit breast cancer by inducing cell cycle arrest and apoptosis through c-Myc/p53 and AKT/14-3-3 pathway

Zhang

Wang

Fan

et al. 2017

Sci Rep

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Our previous studies demonstrated that volatile oil from saussurea lappa root (VOSL), rich in two natural sesquiterpene lactones, costunolide (Cos) and dehydrocostuslactone (Dehy), exerts better anti-breast cancer efficacy and lower side effects than Cos or Dehy alone in vivo, however, their anti-cancer molecular mechanisms were still unknown. In this study, we investigated the underlying mechanisms of Cos and Dehy combination treatment (CD) on breast cancer cells through proteomics technology coupled with Western blot validation. Ingenuity Pathways Analysis (IPA) results based on the differentially expressed proteins revealed that both VOSL and CD affect the 14-3-3-mediated signaling, c-Myc mediated apoptosis signaling and protein kinase A (PKA) signaling. Western blot coupled with cell cycle and apoptosis analysis validated the results of proteomics analysis. Cell cycle arrest and apoptosis were induced in a dose-dependent manner, and the expressions of p53 and p-14-3-3 were significantly up-regulated, whereas the expressions of c-Myc, p-AKT, p-BID were significantly down-regulated, furthermore, the ratio of BAX/BCL-2 were significantly increased in breast cancer cells after CD and VOSL treatment. The findings indicated that VOSL and CD could induce breast cancer cell cycle arrest and apoptosis through c-Myc/p53 and AKT/14-3-3 signaling pathways and may be novel effective candidates for breast cancer treatment.

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Induction of cell cycle arrest and apoptosis by betulinic acid-rich fraction from Dillenia suffruticosa root in MCF-7 cells involved p53/p21 and mitochondrial signalling pathway

Cited by 52 publications

References 51 publications

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

Cisplatin induces HepG2 cell cycle arrest through targeting specific long noncoding RNAs and the p53 signaling pathway

Betulinic Acid: Recent Advances in Chemical Modifications, Effective Delivery, and Molecular Mechanisms of a Promising Anticancer Therapy

Costunolide and dehydrocostuslactone combination treatment inhibit breast cancer by inducing cell cycle arrest and apoptosis through c-Myc/p53 and AKT/14-3-3 pathway

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