HJC, a New Arylnaphthalene Lignan Isolated From Justicia procumbens, Causes Apoptosis and Caspase Activation in K562 Leukemia Cells

Luo, Jiaoyang; Kong, Weijun; Yang, Meihua

doi:10.1254/jphs.13211fp

Cited by 13 publications

(14 citation statements)

References 27 publications

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“…However, excess ROS production would cause severe damage to biomolecules, and then induced apoptosis and/or necrosis [27][28][29]. Additionally, previous studies also showed that lignan compounds are able to induce apoptosis through producing ROS in various cell types [30][31][32][33][34]. Thus, based on aforementioned, we speculated that ROS formation was involved in yatein-mediated cell death.…”

Section: Discussionmentioning

confidence: 79%

Antitumor agent yatein from Calocedrus formosana Florin leaf induces apoptosis in non-small-cell lung cancer cells

Lin

Wu³

et al. 2019

J Wood Sci

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Calocedrus formosana Florin is a softwood tree species with high economic value in Taiwan. Several bioactivities of the extracts of C. formosana have been reported; however, only one study focused on the anti-non-small-cell lung cancer cells' (anti-NSCLC) effect of C. formosana extract and its active phytocompound. In the present study, the anti-lung cancer effects of C. formosana leaf extract and its active derivative yatein were evaluated. The results revealed that the n-hexane fraction of the crude extract exhibited the highest cytotoxicity potential against two non-small-cell lung cancer (NSCLC) cell lines, namely A549 and CL1-5. Yatein, isolated from the n-hexane fraction, exhibited the highest cytotoxicity in the A549 and CL1-5 cells. In addition, the CL1-5 cells were more sensitive than the A549 cells after yatein treatment. Flow cytometry results revealed that yatein induced apoptosis in the two cell lines. Furthermore, expression of regulatory proteins related to apoptosis, such as caspase 3, caspase 8, caspase 9, and poly (ADP-ribose) polymerase (PARP), increased in the A549 and CL1-5 cells after yatein treatment. These findings provide insight into the in vitro anti-lung tumor efficacy of yatein, thus rendering this phytocompound a potential anticancer lead compound for NSCLC treatment.

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Section: Discussionmentioning

confidence: 79%

Antitumor agent yatein from Calocedrus formosana Florin leaf induces apoptosis in non-small-cell lung cancer cells

Lin

Wu³

et al. 2019

J Wood Sci

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“…In this study, our data indicated that sanguinarineinduced cell viability inhibition related to the induction of cell apoptotic death in HSC-T6 cells; the induction of apoptosis was related to the ROS production, which followed by activation of caspases (-3, -6, -8 and -9), decrease of MMP and down-regulation of BCL2 expression. This was consisted with previous studies of Hacat cells (41), human cervical cancer cells (42) and K562 Leukemia Cells (43).…”

Section: Discussionmentioning

confidence: 99%

BCL2 promotor methylation and miR-15a/16-1 upregulation is associated with sanguinarine-induced apoptotic death in rat HSC-T6 cells

Zhang

Chen

et al. 2015

Journal of Pharmacological Sciences

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Previous studies show that several pathways are involved in sanguinarine-induced apoptotic cell death, including AKT downregulation, inhibition of NF-kB activation, mediation of ROS production, downregulation of anti-apoptosis proteins XIAP and cIAP-1, upregulation of BAX, and downregulation of BCL2. In this study, we found out that the quenching of ROS generation by N-acetyl-l-cysteine (NAC), a scavenger of ROS, reversed sanguinarine-induced apoptosis effects, also we found out that sanguinarine-induced rat hepatic stellate T6 cells (HSC-T6 cells) apoptosis was correlated with the generation of increased ROS, which was followed by the activation of caspase-8 (-3, -6, and -9), and the decreasing in the miltochondrial membrane potential (MMP) and the down-regulation of anti-apoptotic protein Bcl-2. It is not clear whether BCL2's downregulation relates to its promoter methylation and miR-15a/16-1 expression which can bind to BCL2 3'-UTR (un-translation reagon). We showed that sanguinarine-induced down regulation of BCL2 was associated with the increased methylation rate of BCL2 promotor district and the increased expression of miR-15a/16-1. HSC-T6 cells treatment with 5-Aza-2'-deoxycytidine (5'-Aza-CdR) impeded sanguinarine-induced BCL2 promotor district methylation and recovered BCL2's expression. Over expression of BCL2 using pEGFP-N1 vector decreased sanguinarine-induced HSC-T6 cells apoptotic death significantly but not completely. These observations clearly showed that BCL2 down regulation was associated with its promoter methylation and miR-15a/16-1 upregulation in sanguinarine-induced Rat HSC-T6 cells.

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“…It is used for the treatment of chronic myeloid leukemia and malignant gastrointestinal stromal tumors in clinical trials. IMA, as a positive drug, showed similar trends as HJB on K562 cells, with a significantly stronger effect than POD and ETO ( Luo et al, 2014b ).…”

Section: Discussionmentioning

confidence: 86%

6′-Hydroxy Justicidin B Triggers a Critical Imbalance in Ca2+ Homeostasis and Mitochondrion-Dependent Cell Death in Human Leukemia K562 Cells

Luo

Qin

et al. 2018

Front. Pharmacol.

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Justicia procumbens (J. procumbens) is a traditional Chinese herbal medicine which was used for the treatment of fever, pain, and cancer. A compound 6′-hydroxy justicidin B (HJB) isolated from J. procumbens exhibits promising biological properties. However, the mechanism of action and the in vivo behavior of HJB remain to be elucidated. In this study, we investigated the mechanism of action of HJB on human leukemia K562 cells and its pharmacokinetic properties in rats. The results demonstrated that HJB significantly inhibited the proliferation of K562 cells and promoted apoptosis. Besides, HJB resulted in decreased mitochondrial membrane potential deltaPSIm, increased the level of the calcium homeostasis regulator protein TRPC6 and cytosolic calcium. The activity of caspase-8, caspase-9 and the expression of p53 were significantly increased after treatment with HJB. Additionally, HJB has rapid absorption rate and relative long elimination t1/2, indicating a longer residence time in vivo. The results indicate that HJB inhibited the proliferation of K562 cells and induced apoptosis by affecting the function of mitochondria and calcium homeostasis to activate the p53 signaling pathway. The pharmacokinetic study of HJB suggested it is absorbed well and has moderate metabolism in vivo. These results present HJB as a potential novel alternative to standard human leukemia therapies.

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HJC, a New Arylnaphthalene Lignan Isolated From Justicia procumbens, Causes Apoptosis and Caspase Activation in K562 Leukemia Cells

Cited by 13 publications

References 27 publications

Antitumor agent yatein from Calocedrus formosana Florin leaf induces apoptosis in non-small-cell lung cancer cells

Antitumor agent yatein from Calocedrus formosana Florin leaf induces apoptosis in non-small-cell lung cancer cells

BCL2 promotor methylation and miR-15a/16-1 upregulation is associated with sanguinarine-induced apoptotic death in rat HSC-T6 cells

6′-Hydroxy Justicidin B Triggers a Critical Imbalance in Ca2+ Homeostasis and Mitochondrion-Dependent Cell Death in Human Leukemia K562 Cells

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