Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.)

Basaiyye, Shriniwas S.; Kashyap, Sanjay M.; Krishnamurthi, Kannan; Sivanesan, Saravanadevi

doi:10.1016/j.joim.2019.03.004

Cited by 10 publications

(10 citation statements)

References 20 publications

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“…TCM has a long history and had attracted lots of researchers’ interests. Nowadays, more efforts were focused on the functionally active chemical compounds isolated from TCM drugs 33,34 . We had a long‐term interest in combining TCM and gene therapy, and have confirmed that several TCM chemical compounds including shikonin, celastrol, and pristimerin can be introduced to improve the hepatocytes of transduction efficiency mediated by rAAV2, rAAV3 or rAAV8 23,24 .…”

Section: Discussionmentioning

confidence: 88%

“…Nowadays, more efforts were focused on the functionally active chemical compounds isolated from TCM drugs. 33,34 We had a long-term interest in combining TCM and gene therapy, and have confirmed that several TCM chemical compounds including shikonin, celastrol, and pristimerin can be introduced to improve the hepatocytes of transduction efficiency mediated by F I G U R E 5 Depletion of ROS reduced shikonin-enhanced rAAV6 transduction efficiency in hematopoietic cells. A and B, K562 cells were treated with 300 nM shikonin for 72 hours.…”

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confidence: 93%

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Mechanism for enhanced transduction of hematopoietic cells by recombinant adeno‐associated virus serotype 6 vectors

Chen

Jia

et al. 2020

FASEB j.

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Hematopoietic gene delivery, such as hematopoietic stem/progenitor cells (HSPCs), is a promising treatment for both inherited and acquired diseases, such as hemophilia. Recently, a combined strategy to achieve more than 90% transduction efficiency was documented using recombinant adeno‐associated virus serotype 6 (rAAV6) vectors. However, the mechanisms of enhanced vector transduction efficiency in hematopoietic cells are largely unknown. In this manuscript, we first reported that proteasome inhibitors, which are well‐known to facilitate rAAV intracellular trafficking in various cell types, are not effective in hematopoietic cells. From the screening of small molecules derived from traditional Chinese medicine, we demonstrated that shikonin, a potential reactive oxygen species (ROS) generator, significantly increased the in vitro and ex vivo transgene expression mediated by rAAV6 vectors in hematopoietic cells, including human cord blood‐derived CD34 + HSPCs. Shikonin mainly targeted vector intracellular trafficking, instead of host cell entry or endonuclear single to double strand vector DNA transition, in a vector serotype‐dependent manner. Moreover, a ROS scavenger completely prevented the capability of shikonin to enhance rAAV6 vector‐mediated transgene expression. Taken together, these studies expand our understanding of rAAV6‐mediated transduction in hematopoietic cells and are informative for improving rAAV6‐based treatment of blood diseases.

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Section: Discussionmentioning

confidence: 88%

mentioning

confidence: 93%

Mechanism for enhanced transduction of hematopoietic cells by recombinant adeno‐associated virus serotype 6 vectors

Chen

Jia

et al. 2020

FASEB j.

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“…We also used DNA gel electrophoresis to confirm that ATRA combined with BDMC have higher apoptosis than that of ATRA and BDMC treated alone (Figure 3c). FITC-Annexin V/PI double staining, DAPI staining for DNA condensation, and DNA fragmentation showing 200-bp DNA ladder has been recognized to be acceptable methods for examining cell apoptosis (Basaiyye, Kashyap, Krishnamurthi, & Sivanesan, 2019;Jiang et al, 2017;Mannarreddy et al, 2017;Zhang et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Combinational treatment of all‐trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC)‐induced apoptosis in liver cancer Hep3B cells

et al. 2019

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The effects of two-drug combination, all-trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC), on apoptosis induction of liver cancer cells were investigated in human liver Hep 3B cells. Two-drug combination caused a more effective decrease in cell viability and in induction of S phase arrest, DNA damage, and cell apoptosis than that of ATRA or BDMC only. Also, the two-drug combination caused more cells to undergo significantly increased ROS productions when compared to that of ATRA or BDMC only. Results of Western blotting demonstrated that two-drug combination increased expressions of Fas, pro-apoptotic proteins, and active form of caspase-3 and -9, but decreased that of anti-apoptotic proteins and XIAP than that of ATRA or BDMC only in Hep 3B cells. In conclusion, ATRA combined with BDMC enhance cell apoptosis and associated protein expression in Hep 3B cells. Practical applicationsBisdemethoxycurcumin (BDMC) derived from natural plants, turmeric (Curcuma longa), which had been used for Asia food for thousands of years. All-trans retinoid acid (ATRA) is currently used as a primary treatment for patients with acute

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“…To the best of our knowledge, our demonstration of L. sativum methanolic extracts (CRU-MeOH and SOX-MeOH)-mediated increments in cell death is the first of its kind in terms of specifically determining its relative MTT-based cytotoxic potential (Figure 1) correlated with PI-mediated, flow cytometrybased cell death assays in MCF-7 cells (Figure 2). Previous studies have shown that that L. sativum extracts can induce cytotoxicity in the MCF-7, 7 Jurkat E6-1 cells 18 and HepG2 19 cells, following treatment over a 24-48 hr time period. Our MTT data and flow cytometry data suggest that CRU-MeOH and SOX-MeOH extract have produced a statistically significant increase in cytotoxicity in the MCF-7 cell line at concentrations of 88.49 µg/ml, and 136.75 µg/ml respectively in comparison with that of the negative and vehicle controls.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Cell Death Potential of Lepidium sativum Seed Extracts in MCF-7 Cells and Molecular Docking-based Correlation of Identified Bioactive Components with Human Caspase-6 Protein

Rajasekaran¹,

Suresh²

2022

IJPER

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Aim and Background:The methanolic extract of Lepidium sativum L. was known for its free radical scavenging potential and anticancer properties. The aim was to perform a comparative investigation of the cytotoxic and cell death potential of the Soxhlet (SOX) and crude methanolic extract (CRU). `Materials and Methods: MTT as well as the PI-based assays in caspase-3-deficient, MCF-7 human breast cancer cells, for its cytotoxic potential and synergistic effect. LC-QTOF-MS/MS was used for characterization. These bioactive molecules were docked with human caspase-6 (2WDP) as well as its zymogen variant (4IYR) to mimicking a more physiological form of cell demise. Results: Both extracts showed a dose-dependent toxicity and the IC 50 was found to be 136.75µg/ml, and 88.49 µg/ml compared with that of standard quercetin (8.72µg/ml). At their IC 50 concentrations, the corresponding PI-based flow cytometry and cell death values were 31.5±3% and 32.4±5.6, while that of quercetin was 36.9±7.4 %. A synergy in cell death was seen for a combination of L. sativum extracts (CRU-MeOH & SOX-MeOH) and quercetin. Thirteen (13) compounds were reported for the first time in this seed by LC-MS/MS. Good binding affinity was seen with both human caspase -6 (2WDP) and the mutated zymogen (4IYR) with reference to that of quercetin. Conclusion: This in vitro/in silico correlation showed that the methanolic extracts of L. sativum exhibited a significantly higher level of cell death in MCF-7 cells. Also, their synergistic increases in cell death provides a basis possibly for a combination therapy-based strategy.

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Induction of apoptosis in leukemic cells by the alkaloid extract of garden cress (Lepidium sativum L.)

Cited by 10 publications

References 20 publications

Mechanism for enhanced transduction of hematopoietic cells by recombinant adeno‐associated virus serotype 6 vectors

Mechanism for enhanced transduction of hematopoietic cells by recombinant adeno‐associated virus serotype 6 vectors

Combinational treatment of all‐trans retinoic acid (ATRA) and bisdemethoxycurcumin (BDMC)‐induced apoptosis in liver cancer Hep3B cells

Evaluation of Cell Death Potential of Lepidium sativum Seed Extracts in MCF-7 Cells and Molecular Docking-based Correlation of Identified Bioactive Components with Human Caspase-6 Protein

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