Crude Extracts, Flavokawain B and Alpinetin Compounds from the Rhizome of Alpinia mutica Induce Cell Death via UCK2 Enzyme Inhibition and in Turn Reduce 18S rRNA Biosynthesis in HT-29 Cells

Malami, Ibrahim; Abdul, Ahmad Bustamam; Abdullah, Rasedee; Kassim, Nur Kartinee; Rosli, Rozita; Yeap, Swee Keong; Waziri, Peter; Etti, Imaobong Christopher; Bello, Muhammad Bashir

doi:10.1371/journal.pone.0170233

Cited by 30 publications

(32 citation statements)

References 56 publications

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“…Across these studies, there was unanimous agreement that FKB had antiproliferative ability with the majority of papers reporting induction of G2/M arrest . One paper suggested FKB induced G0/G1 arrest . Additionally, there was a general consensus that FKB induced apoptosis .…”

Section: Resultsmentioning

confidence: 99%

“…Fourteen papers reported cell cycle arrest by FKA, FKB and/or FKC, at G2/M or G1 . Cells accumulated in the G2/M phase undergo apoptosis through the Bax‐initiated mitochondrial pathway .…”

Section: Discussionmentioning

confidence: 99%

“…16,20,21,23,25,27,29,32,[51][52][53] One paper suggested FKB induced G0/G1 arrest. 35 Additionally, there was a general consensus that FKB induced apoptosis. 16,18,20,21,23,25,27,29,32,35,49,50,53,54 Proposed mechanisms included increased expression of pro-apoptotic proteins, such as PUMA, Bim and Bax expression 23,27,49,50,53 ; decreased expression of anti-apoptotic proteins, such as survivin and XIAP, 20,23,27 ROS production 21,25,29,32,50 ; or increase in caspase 3, 7, 8, and or 9.…”

Section: Flavokavain B (Fkb)mentioning

confidence: 99%

“…35 Additionally, there was a general consensus that FKB induced apoptosis. 16,18,20,21,23,25,27,29,32,35,49,50,53,54 Proposed mechanisms included increased expression of pro-apoptotic proteins, such as PUMA, Bim and Bax expression 23,27,49,50,53 ; decreased expression of anti-apoptotic proteins, such as survivin and XIAP, 20,23,27 ROS production 21,25,29,32,50 ; or increase in caspase 3, 7, 8, and or 9. 27,50 Three studies suggested apoptosis may have been induced via PARP cleavage, 20,32,49,50 although interestingly a single study reported that apoptosis was induced in the absence of PARP cleavage.…”

Section: Flavokavain B (Fkb)mentioning

confidence: 99%

“…Of these papers,27 presented in vitro assessment and 10 in vivo, which were mainly conducted in mice, and a zebrafish model 17,18,28,[30][31][32]34,[37][38][39]43,45,49,50. Fourteen papers reported cell cycle arrest by FKA, FKB and/or FKC, at G2/M18,20,21,23,[25][26][27]29,30,32,[51][52][53] or G1 30,35. Cells accumulated in the G2/M phase undergo apoptosis through the Bax-initiated mitochondrial pathway.…”

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confidence: 99%

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The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review

Celentano

Tran

Testa

et al. 2019

J Oral Pathology Medicine

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Background Kava is a beverage made from the ground roots of the plant Piper Methysticum and has long‐held a significant place within Pacific island communities. Active compounds were extracted from kava, and secondary metabolites include kavalactones, chalcones, cinnamic acid derivatives and flavanones. It is thought that components of kava may exert an antiproliferative effect through cell cycle arrest and promotion of apoptosis. Methods We conducted a systematic review to summarize available evidence of the anticancer effects of kava components and investigate their potential use for oral squamous cell carcinoma (OSCC) treatment. Eligible studies were identified through a comprehensive search of OVID EMBASE, OVID MEDLINE and Web of Science, as at April 2018. Results Of 39 papers that met the inclusion criteria, 32 included in vitro models and 13 included animal studies. A total of 26 different cancers were assessed with 32 studies solely assessing epithelial cancers, 6 mesenchymal cancers and 1 study including both. There was only one report assessing an OSCC cell line. Antiproliferative properties were demonstrated in 32 out of 39 papers. The most researched constituent of kava was flavokavain B followed by flavokavain A. Both were associated with increased expression of pro‐apoptotic proteins and decreased expression of anti‐apoptotic proteins. Further, they were associated with a dose‐dependent reduction of angiogenesis. Conclusion There was heterogeneity of study models and methods of investigation across the studies identified. Components of kava appear to present an area of interest with chemotherapeutic potential in cancer prevention and treatment, particularly for epithelial neoplasms. To date, there is a paucity of literature of the utility of kava components in the prevention and treatment of oral squamous cell carcinoma.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Flavokavain B (Fkb)mentioning

confidence: 99%

Section: Flavokavain B (Fkb)mentioning

confidence: 99%

mentioning

confidence: 99%

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The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review

Celentano

Tran

Testa

et al. 2019

J Oral Pathology Medicine

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UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma

Guo

et al. 2018

IUBMB Life

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Uridine‐cytidine kinases (encoded by UCK1, UCKL1, and UCK2) catalyze the phosphorylation of uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP). In this study, using data from the Cancer Genome Atlas (TCGA), we analyzed the expression profile of uridine‐cytidine kinase genes in hepatocellular carcinoma (HCC), their prognostic value, and the epigenetic alterations associated with their dysregulation. Results showed that UCKL1 and UCK2, but not UCK1 were significantly upregulated in HCC tissues than in adjacent normal tissues. Only UCK2 was significantly upregulated in the deceased group and the recurrence group, compared to the control groups. Multivariate analysis confirmed that increased UCK2 expression was an independent prognostic indicator of shorter overall survival (OS) (HR: 1.760, 95% CI: 1.398–2.216, P < 0.001) and recurrence‐free survival (RFS) (HR: 1.543, 95% CI: 1.232–1.933, P < 0.001). Two CpG sites (cg09277749 and cg21143899) were significantly hypomethylated in HCC tissues than in adjacent normal tissues and were negatively correlated with UCK2 expression. However, survival analysis showed that only high methylation of cg0927774 was associated with better OS and RFS of HCC patients. Based on the findings above, we infer that UCK2 upregulation might be a valuable prognostic marker in HCC. The methylation of status cg0927774 might play a critical role in its expression. © 2018 IUBMB Life, 71(1):105–112, 2019

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The discovery of a novel eight‐mRNA‐lncRNA signature predicting survival of hepatocellular carcinoma patients

Shi

Lin

et al. 2018

J of Cellular Biochemistry

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Increasing evidence indicates that the expressions of messenger RNAs (mRNAs) and long non‐coding RNAs (lncRNAs) undergo a frequent and aberrant change in carcinogenesis and cancer development. But some research was carried out on mRNA‐lncRNA signatures for prediction of hepatocellular carcinoma (HCC) prognosis. We aimed to establish an mRNA‐lncRNA signature to improve the ability to predict HCC patients’ survival. The subjects from the cancer genome atlas (TCGA) data set were randomly divided into two parts: training data set (n = 246) and testing data set (n = 124). Using computational methods, we selected eight gene signatures (five mRNAs and three lncRNAs) to generate the risk score model, which were significantly correlated with overall survival of patients with HCC in both training and testing data set. The signature had the ability to classify the patients in training data set into a high‐risk group and low‐risk group with significantly different overall survival (hazard ratio = 4.157, 95% confidence interval = 2.648‐6.526, P < 0.001). The prognostic value was further validated in testing data set and the entire data set. Further analysis revealed that this signature was independent of tumor stage. In addition, Gene Set Enrichment Analysis suggested that high risk score group was associated with cell proliferation and division related pathways. Finally, we developed a well‐performed nomogram integrating the prognostic signature and other clinical information to predict 3‐ and 5‐year overall survival. In conclusion, the prognostic mRNAs and lncRNAs identified in our study indicate their potential role in HCC biogenesis. The risk score model based on the mRNA‐lncRNA may be an efficient classification tool to evaluate the prognosis of patients’ with HCC.

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Crude Extracts, Flavokawain B and Alpinetin Compounds from the Rhizome of Alpinia mutica Induce Cell Death via UCK2 Enzyme Inhibition and in Turn Reduce 18S rRNA Biosynthesis in HT-29 Cells

Cited by 30 publications

References 56 publications

The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review

The protective effects of Kava (Piper Methysticum) constituents in cancers: A systematic review

UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma

The discovery of a novel eight‐mRNA‐lncRNA signature predicting survival of hepatocellular carcinoma patients

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