Dataset Information

Cell Cycle Arrest and Apoptosis in HT-29 Cells Induced by Dichloromethane Fraction From Toddalia asiatica (L.) Lam.

ABSTRACT: The roots of Toddalia asiatica (L.) Lam. (TA) has been often used in Chinese folk medicine to treat different diseases, including but not limited to arthritis, injuries, stomachache, and even tumors. However, the anti-cancer effects and the action mechanisms of TA remain elusive. Therefore, we firstly evaluated the effects of different extracts of TA on the growth of human colon cancer cells, and then tried to further elucidate their underlying molecular mechanisms. As a result, the dichloromethane fraction (DF) was found to possess the highest anti-proliferative activity with IC₅₀ value at 18 ?g/mL among all of the four extracts from TA, and strongly inhibited HT-29 cell growth and halted cell cycle progression in G2/M phase. DF also induced phosphatidylserine externalization and activated caspases -8, -9, and -3, suggesting DF induced apoptosis through intrinsic and extrinsic pathways. Furthermore, we found that HT-29 cell cycle arrest induced by DF could be the result of reactive oxygen species (ROS), as the ROS scavenger N-acetyl cysteine (NAC) attenuating it. Taken together, these results indicated that DF induced cell cycle arrest at G2/M phase and apoptosis in HT-29 cells, and could be a promising source for developing natural therapeutics for colon cancer.

SUBMITTER: Li X

PROVIDER: S-EPMC6008524 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Cell Cycle Arrest and Apoptosis in HT-29 Cells Induced by Dichloromethane Fraction From <i>Toddalia asiatica</i> (L.) Lam.

Li Xun X Qiu Zidong Z Jin Qinghao Q Chen Guilin G Guo Mingquan M

Frontiers in pharmacology 20180612

The roots of <i>Toddalia asiatica</i> (L.) Lam. (TA) has been often used in Chinese folk medicine to treat different diseases, including but not limited to arthritis, injuries, stomachache, and even tumors. However, the anti-cancer effects and the action mechanisms of TA remain elusive. Therefore, we firstly evaluated the effects of different extracts of TA on the growth of human colon cancer cells, and then tried to further elucidate their underlying molecular mechanisms. As a result, the dichl ...[more]

PMID: 29950999

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Project description:In the present study, two samples of Toddalia asiatica species, both collected from Kenya, were sequenced and comparison of their genome structures carried out with T. asiatica species from China, available in the NCBI database. The genome size of both species from Africa was 158, 508 base pairs, which was slightly larger, compared to the reference genome of T. asiatica from Asia (158, 434 bp). The number of genes was 113 for both species from Africa, consisting of 79 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. Toddalia asiatica from Asia had 115 genes with 81 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. Both species compared displayed high similarity in gene arrangement. The gene number, orientation, and order were highly conserved. The IR/SC boundary structures were the same in all chloroplast genomes. A comparison of pairwise sequences indicated that the three regions (trnH-psbA, rpoB, and ycf1) were more divergent and can be useful in developing effective genetic markers. Phylogenetic analyses of the complete cp genomes and 79 protein-coding genes indicated that the Toddalia species collected from Africa were sister to T. asiatica collected from Asia. Both species formed a sister clade to the Southwest Pacific and East Asian species of Zanthoxylum. These results supported the previous studies of merging the genus Toddalia with Zanthoxylum and taxonomic change of Toddalia asiatica to Zanthoxylum asiaticum, which should also apply for the African species of Toddalia. Biogeographic results demonstrated that the two samples of Toddalia species from Africa diverged from T. asiatica from Asia (3.422 Mya, 95% HPD). These results supported an Asian origin of Toddalia species and later dispersal to Africa and Madagascar. The maxent model analysis showed that Asia would have an expansion of favorable areas for Toddalia species in the future. In Africa, there will be contraction and expansion of the favorable areas for the species. The availability of these cp genomes will provide valuable genetic resources for further population genetics and biogeographic studies of these species. However, more T. asiatica species collected from a wide geographical range are required.

Project description:Chalcones have been shown to exhibit anti-cancer properties by targeting multiple molecular pathways. It was, therefore, of interest to investigate flavokawain C (FKC), a naturally occurring chalcone, which can be isolated from Kava (Piper methysticum Forst) root extract. The aim of this study was to investigate the inhibitory effect of FKC on the growth of HT-29 cells and its underlying mechanism of action. Cell viability of HT-29 cells was assessed by Sulforhodamine B assay after FKC treatment. Induction of apoptosis was examined by established morphological and biochemical assays. ROS generation was determined by dichlorofluorescein fluorescence staining, and superoxide dismutase activity was measured using the spectrophotometric method. Western blotting was used to examine the changes in the protein levels. FKC markedly decreased the cell viability of HT-29 cells and the cells showed dramatic changes in cellular and nuclear morphologies with typical apoptotic features. The induction of apoptosis correlated well with the externalization of phosphatidylserine, DNA fragmentation, decreased mitochondrial membrane potential, activation of caspases, and PARP cleavage. This was associated with an increase in reactive oxygen species and a decrease in SOD activity. The protein levels of XIAP, c-IAP1, and c-IAP2 were downregulated, whereas the GADD153 was upregulated after FKC treatment. FKC induced cell cycle arrest at the G1 and G2/M phases via upregulation of p21 and p27 in a p53-independent manner. Our results provide evidence that FKC has the potential to be developed into chemotherapeutic drug for the treatment of colon adenocarcinoma.Flavokawain C inhibited the growth of HT-29 human colon adenocarcinoma cellsFlavokawain C induced apoptosis in HT-29 cells, associated with an increase in reactive oxygen species and a decrease in SOD activityFlavokawain C induced cell cycle arrest at the G1 and G2/M phases via upregulation of p21 and p27 in HT-29 cellsHT-29 cells treated with flavokawain C caused downregulation of XIAP, c-IAP1, and c-IAP2, and upregulation of GADD153. Abbreviations used: FKC: Flavokawain C; SRB: Sulforhodamine B; ROS: Reactive oxygen species; SOD: Superoxide dismutase; PARP: Poly(ADP-ribose) polymerase; ER: Endoplasmic reticulum; IAPs: Inhibitor of apoptosis proteins; TUNEL: Transferase dUTP nick end labeling; Annexin V-FITC: Annexin V conjugated with fluorescein isothicyanate.

Dataset Information

Cell Cycle Arrest and Apoptosis in HT-29 Cells Induced by Dichloromethane Fraction From Toddalia asiatica (L.) Lam.

Publications

Cell Cycle Arrest and Apoptosis in HT-29 Cells Induced by Dichloromethane Fraction From <i>Toddalia asiatica</i> (L.) Lam.

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