Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

Yadav, Poonam; Yadav, Ramakant; Jain, Shweta; Vaidya, Ankur

doi:10.1111/cbdd.13860

Cited by 74 publications

(52 citation statements)

References 100 publications

(90 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Besides, there observed a dose-dependent upsurge in the expression of Apaf-1 and caspase 3/7 genes in A. tetracantha leaf extract-treated cells. Apaf-1 and caspase 3/7 are involved in apoptotic cell death by activating the mitochondrial-mediated intrinsic pathway ( Yadav et al, 2021 ). Previous studies have indicated that the individual flavonoid compounds reported in the LCMS analysis of A. tetracantha independently induce apoptosis in various cancer cells including those of mammary in origin ( Ávila‐Gálvez et al, 2021Ávila‐Gálvez et al, 2021Ávila‐Gálvez et al, 2021 , Malayil et al, 2020 ).…”

Section: Discussionmentioning

confidence: 99%

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

Malayil

Jose²,

Narayanankutty³

et al. 2021

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

Azima tetracantha, a traditional medicinal plant included in the order Brassicales and family Salvadoraceae, is widely used as a dietary supplement in folklore medicines. The plant is also used for the treatment of rheumatism, diarrhea and other inflammatory disorders. The present investigation focused on the phytochemical composition, radical scavenging, reducing potential and anti-proliferative activities of the A. tetracantha leaves. Quantitative estimation of the polyphenols and flavonoids revealed significantly elevated levels in the methanol extract. Corroborating with this, methanol extract exhibited higher in vitro anti-radical scavenging effect against 2,2-diphenyl-1- picrylhydrazyl (34.14 ± 2.19 μg/mL), and hydrogen peroxide (44.96 ± 1.77 μg/mL), as well as ferric reducing properties (58.24 ± 6.98 μg/mL). The methanolic extract also showed strong lipoxygenase (71.42 ± 6.36 μg/mL) and nitric oxide inhibitory activities (94.23 ± 8.11 μg/mL). Cytotoxic activity against MCF7 cells was found to be higher (IC50= 37.62 ± 2.94 μg/mL), than that of MDAMB231 cells (IC50= 69.11 ± 5.02 μg/mL). The qPCR-based analysis indicated dose-dependent increase in the expression of the pro-apoptotic genes such as executioner caspases and apoptotic protease activating factor-1. Overall, the results indicated the possible use of methanol extract of A. tetracantha leaves as a chain-breaking antioxidant molecule and are capable of inhibiting inflammatory enzymes and the proliferative potential of breast cancer cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

Malayil

Jose²,

Narayanankutty³

et al. 2021

Saudi Journal of Biological Sciences

View full text Add to dashboard Cite

show abstract

“…PARP is one of the major apoptotic markers and is responsible for repairing stress or DNA damage. PARP is converted to cleaved-PARP, a classical substrate for caspase 3, which leads to cell lysis or death ( Wang et al, 2018 ; Yadav et al, 2021 ). As shown in Figure 2E , CA upregulated the expression of cleaved-PARP and cleaved-caspase.…”

Section: Resultsmentioning

confidence: 99%

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway

Wang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Ovarian cancer is one of the most common gynecological malignancies in women worldwide with a poor survival rate. Cinnamaldehyde (CA), a bioactive substance isolated from cinnamon bark, is a natural drug and has shown that it can inhibit the progression of other tumors. However, the role of CA in ovarian cancer and its mechanism is poorly understood. In this study, wound healing assays, plate cloning, CCK-8, and transwell assays were used to determine cell proliferation and invasion. Western blot and flow cytometry were used to detect apoptosis levels. Western blot and immunofluorescence were used to detect changes in cellular EMT levels. The Western blot was used to detect levels of the PI3K/AKT signaling pathway. In vivo, we established a subcutaneous transplantation tumor model in nude mice to verify the role of CA in the progression and metastasis of ovarian cancer. Our data showed that in vitro CA was able to inhibit the cell viability of ovarian cancer. The results of scratch assay and transwell assay also showed that CA inhibited the proliferation and invasion ability of A2780 and SKOV3 cells. In addition, CA promoted apoptosis by increasing the expression of cleaved-PARP and cleaved-caspase 3 in ovarian cancer cells. Mechanistically, we found that CA inhibited the EGF-induced PI3K/AKT signaling pathway and reduced the phosphorylation levels of mTOR, PI3K, and AKT. The EGF-induced EMT process was also abolished by CA. The EMT process induced by AKT-specific activator SC79 was also suppressed by CA. Furthermore, in in vivo, CA significantly repressed the progression of ovarian cancer as well as liver metastasis. In all, our results suggest that CA inhibits ovarian cancer progression and metastasis in vivo and in vitro and inhibits EGF-induced EMT processes through the PI3K/AKT signaling pathway.

show abstract

“…In the apoptosis cascade, after Δψm depolarization, Cyt c release, and Apaf-1 formation, the activation of “apical” caspases 2, 8, 9, and 10 directly cleaves “effector” caspases; caspases-3 and 7 are the main proteolytic enzymes of intracellular substrates in the final steps of cell death [ 56 ]. The CellEvent Caspase-3/7 Green reagent can estimate the activation of caspase-3/7 in apoptotic cells through a fluorogenic signal [ 57 ].…”

Section: Discussionmentioning

confidence: 99%

The Antitumoral/Antimetastatic Action of the Flavonoid Brachydin A in Metastatic Prostate Tumor Spheroids In Vitro Is Mediated by (Parthanatos) PARP-Related Cell Death

et al. 2022

View full text Add to dashboard Cite

Metastatic prostate cancer (mPCa) is resistant to several chemotherapeutic agents. Brachydin A (BrA), a glycosylated flavonoid extracted from Fridericia platyphylla, displays a remarkable antitumoral effect against in vitro mPCa cells cultured as bidimensional (2D) monolayers. Considering that three-dimensional (3D) cell cultures provide a more accurate response to chemotherapeutic agents, this study investigated the antiproliferative/antimetastatic effects of BrA and the molecular mechanisms underlying its action in mPCa spheroids (DU145) in vitro. BrA at 60–100 μM was cytotoxic, altered spheroid morphology/volume, and suppressed cell migration and tumor invasiveness. High-content analysis revealed that BrA (60–100 µM) reduced mitochondrial membrane potential and increased apoptosis and necrosis markers, indicating that it triggered cell death mechanisms. Molecular analysis showed that (i) 24-h treatment with BrA (80–100 µM) increased the protein levels of DNA disruption markers (cleaved-PARP and p-γ-H2AX) as well as decreased the protein levels of anti/pro-apoptotic (BCL-2, BAD, and RIP3K) and cell survival markers (p-AKT1 and p-44/42 MAPK); (ii) 72-h treatment with BrA increased the protein levels of effector caspases (CASP3, CASP7, and CASP8) and inflammation markers (NF-kB and TNF-α). Altogether, our results suggest that PARP-mediated cell death (parthanatos) is a potential mechanism of action. In conclusion, BrA confirms its potential as a candidate drug for preclinical studies against mPCa.

show abstract

Caspase‐3: A primary target for natural and synthetic compounds for cancer therapy

Cited by 74 publications

References 100 publications

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

Phytochemical profiling of Azima tetracantha Lam. leaf methanol extract and elucidation of its potential as a chain-breaking antioxidant, anti-inflammatory and anti-proliferative agent

Cinnamaldehyde Suppressed EGF-Induced EMT Process and Inhibits Ovarian Cancer Progression Through PI3K/AKT Pathway

The Antitumoral/Antimetastatic Action of the Flavonoid Brachydin A in Metastatic Prostate Tumor Spheroids In Vitro Is Mediated by (Parthanatos) PARP-Related Cell Death

Contact Info

Product

Resources

About