Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells

Kim, Young Ho; Kim, Guen Tae; Kim, Bo Min; Lim, Eun Gyeong; Kim, Sang-Yong; Kim, Young Min

doi:10.1186/s12906-017-1702-7

Cited by 34 publications

(19 citation statements)

References 33 publications

(24 reference statements)

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“…Another study conducted by Worku et al reported the cytotoxic effect of this extract on solid tumor cell lines such as prostate cancer cells 20 . Moreover, Eun Ji Kim indicated that AAE could exert an apoptotic effect on colon cancer cells 21 . In an effort to investigate the potential therapeutic value of AAE, for the first time, we aimed to evaluate the restrictive effect of methanolic extract from aerial parts of Artemisia annua on both Nalm-6 and Reh cell lines alone and in combination with VCR.…”

Section: Discussionmentioning

confidence: 99%

Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells

Mashati

Esmaeili

Dehghan-Nayeri

et al. 2019

IJHOSCR

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Background: Nowadays, remarkable attention has been drawn towards the effective therapeutic characteristic of natural products targeting cancerous cells. This study aimed to investigate the anti-cancer effect of Artemisia annua extract (AAE), a Chinese herbal medicine alone and in combination with a microtubule binding agent used in ALL treatment, vincristine (VCR), in B-Acute lymphoblastic leukemia (ALL) Nalm-6 and Reh cells. Materials and Methods: Cytotoxic activity of AAE and VCR was determined using MTT assay in Nalm-6, and Reh cell lines and synergism was evaluated using the CompuSyn software. Caspase 3 activity and Annexin/PI staining were performed for apoptosis assessment. The expression level of apoptosis-related genes, caspase 3, Bax and Bcl-2 were determined using real time-PCR. One-way ANOVA and post hoc Tukey multiple comparisons were used for statistical analysis. Results: Our findings revealed that a single administration of AAE exerted an anti-leukemic effect in both ALL-derived cells in a time- and dose-dependent manner. Interestingly, the growth inhibitory activity of the extract was more potentiated when combined with 0.1 and 1 nM VCR through caspase 3-dependent apoptosis. Moreover, real-time PCR analysis showed that VCR-induced cytotoxicity was augmented by AAE through alteration of Bax, and Bcl-2 mRNA expression. Conclusion: Overall, owing to the nontoxic nature of AAE and its explicit role in enhancing VCR effectiveness, our study provided new insight into the development of a novel combinatorial approach in ALL using natural herbs. The practical implication of the research requires further investigation through clinical trials, opening avenues for forthcoming treatment improvements.

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Section: Discussionmentioning

confidence: 99%

Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells

Mashati

Esmaeili

Dehghan-Nayeri

et al. 2019

IJHOSCR

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“…We also found that the loss of PDK1 in the developing dentate gyrus causes unbalanced cell proliferation and neurogenesis [32]. A growing amount of evidence suggests that PDK1 is upregulated in cancer cells and required for cell survival [33][34][35]. All these studies demonstrate that PDK1 plays different roles during different biological processes.…”

Section: Introductionmentioning

confidence: 64%

PDK1 regulates the survival of the developing cortical interneurons

2020

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Inhibitory interneurons are critical for maintaining the excitatory/inhibitory balance. During the development cortical interneurons originate from the ganglionic eminence and arrive at the dorsal cortex through two tangential migration routes. However, the mechanisms underlying the development of cortical interneurons remain unclear. 3-Phosphoinositide-dependent protein kinase-1 (PDK1) has been shown to be involved in a variety of biological processes, including cell proliferation and migration, and plays an important role in the neurogenesis of cortical excitatory neurons. However, the function of PDK1 in interneurons is still unclear. Here, we reported that the disruption of Pdk1 in the subpallium achieved by crossing the Dlx5/6-Cre-IRES-EGFP line with Pdk1 fl/fl mice led to the severely increased apoptosis of immature interneurons, subsequently resulting in a remarkable reduction in cortical interneurons. However, the tangential migration, progenitor pools and cell proliferation were not affected by the disruption of Pdk1. We further found the activity of AKT-GSK3β signaling pathway was decreased after Pdk1 deletion, suggesting it might be involved in the regulation of the survival of cortical interneurons. These results provide new insights into the function of PDK1 in the development of the telencephalon.

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“…Kim et al [34] evaluated the effect of an A. annua extract on human colon cancer cell line HCT116 and found that cell cycle arrest occurred at the G 1 /S phase mediated by the Akt/mTOR pathway. Later on, they demonstrated that A. annua extract induced apoptosis through the regulation of specific proteins such as Bax, Bak, and cytochrome c in PDK1/Akt signaling pathways via a PTEN/p53-independent manner [35]. In this work, cell cycle analysis suggested that a modified cellular distribution in different phases of the cycle occurred in the treated cells and that the sub-G1 peak observed was due to cellular debris rather than fragmented DNA, which is typical of apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Cytotoxic Effects of Artemisia annua L. and Pure Artemisinin on the D-17 Canine Osteosarcoma Cell Line

Isani

Bertocchi

Andreani

et al. 2019

Oxidative Medicine and Cellular Longevity

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Artemisia annua has been used for centuries in Traditional Chinese Medicine. Although used as an antimalarial drug, its active compound artemisinin and the semisynthetic derivatives have also been investigated for their anticancer properties, with interesting and promising results. The aims of this research were to evaluate (i) the cytotoxicity and the antiproliferative effect of pure artemisinin and a hydroalcoholic extract obtained from A. annua on the D-17 canine osteosarcoma cell line and (ii) the intracellular iron concentration and its correlation with the cytotoxic effects. Both artemisinin and hydroalcoholic extract induced a cytotoxic effect in a dose-dependent manner. Pure artemisinin caused an increase of cells in the S phase, whereas the hydroalcoholic extract induced an evident increase in the G2/M phase. A significant decrease of iron concentration was measured in D-17 cells treated with pure artemisinin and hydroalcoholic extract compared to untreated cells. In conclusion, although preliminary, the data obtained in this study are indicative of a more potent cytotoxic activity of the hydroalcoholic extract than pure artemisinin, indicating a possible synergistic effect of the phytocomplex and a mechanism of action involving iron and possibly ferroptosis. Considering the similarities between human and canine osteosarcomas, progress in deepening knowledge and improving therapeutic protocols will probably be relevant for both species, in a model of reciprocal translational medicine.

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Apoptosis-induced effects of extract from Artemisia annua Linné by modulating PTEN/p53/PDK1/Akt/ signal pathways through PTEN/p53-independent manner in HCT116 colon cancer cells

Cited by 34 publications

References 33 publications

Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells

Methanolic Extract from Aerial Parts of Artemisia Annua L. Induces Cytotoxicity and Enhances Vincristine-Induced Anticancer Effect in Pre-B Acute Lymphoblastic Leukemia Cells

PDK1 regulates the survival of the developing cortical interneurons

Cytotoxic Effects of Artemisia annua L. and Pure Artemisinin on the D-17 Canine Osteosarcoma Cell Line

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