Growth-Suppressive and Apoptosis-Inducing Effects of Tetrandrine in SW872 Human Malignant Liposarcoma Cells via Activation of Caspase-9, Down-Regulation of XIAP and STAT-3, and ER Stress

Samsuzzaman, Mohammed; Jang, Byeong‐Churl

doi:10.3390/biom12060843

Cited by 4 publications

(4 citation statements)

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“…To further verify the antiapoptotic effect of NDRG2, 661W cells were pretreated with the apoptosis inhibitor, Z‐VAD‐FMK, in an MNU‐induced model. Z‐VAD‐FMK is a pan‐caspase inhibitor that irreversibly modifies the active‐site cysteine and widely used to study the molecular mechanisms involved in apoptosis [50–53]. In this study, Z‐VAD‐FMK pretreatment alleviated 661W cell apoptosis induced by NDRG2 knockdown, further demonstrating the antiapoptotic effect of NDRG2 on photoreceptors.…”

Section: Discussionsupporting

confidence: 55%

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Chen,

Xiong,

Deng

et al. 2023

The FEBS Journal

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Photoreceptor apoptosis is the main pathological feature of retinal degenerative diseases; however, the underlying molecular mechanism has not been elucidated. Recent studies have shown that N‐myc downstream regulated gene 2 (NDRG2) exerts a neuroprotective effect on the brain and spinal cord. In addition, our previous studies have confirmed that NDRG2 is expressed in mouse retinal photoreceptors and counteracts N‐methyl‐N‐nitrosourea (MNU)‐induced apoptosis. However, the underlying molecular mechanism remains unclear. In this study, we observed that the expression of NDRG2 was not only significantly inhibited in photoreceptors after MNU treatment but also after hydrogen peroxide treatment, and photoreceptor apoptosis was alleviated or aggravated after overexpression or knockdown of NDRG2 in the 661W photoreceptor cell line, respectively. The apoptosis inhibitor Z‐VAD‐FMK rescued photoreceptor apoptosis induced by MNU after NDRG2 knockdown. Next, we screened and identified tissue inhibitor of metalloproteinases 3 (TIMP3) as the downstream molecule of NDRG2 in 661W cells by using quantitative real‐time polymerase chain reaction. TIMP3 exerts a neuroprotective effect by inhibiting the expression of matrix metalloproteinases (MMPs). Subsequently, we found that signal transducer and activator of transcription 3 (STAT3) mediated the NDRG2‐associated regulation of TIMP3. Finally, we overexpressed NDRG2 in mouse retinal tissues by intravitreally injecting an adeno‐associated virus with mouse NDRG2 in vivo. Results showed that NDRG2 upregulated the expression of phospho‐STAT3 (p‐STAT3) and TIMP3, while suppressing MNU‐induced photoreceptor apoptosis and MMP expression. Our findings revealed how NDRG2 regulates the STAT3/TIMP3/MMP pathway and uncovered the molecular mechanism underlying its neuroprotective effect on mouse retinal photoreceptors.

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Section: Discussionsupporting

confidence: 55%

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Chen,

Xiong,

Deng

et al. 2023

The FEBS Journal

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“…In both pathways, caspases are activated and participate in apoptosis by cleaving their downstream factors, such as PARP and other important proteins (Zaman). At the basal level, caspases are synthesized in an inactive zymogen form; however, upon activation, they play a significant role in apoptosis ( Samsuzzaman and Jang, 2022 ). Next, we investigated whether GA-induced reduction in cell density or morphological changes were associated with the activation of the apoptosis pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Apoptosis is an event of programmed cell death, characterized by morphological changes, cell shrinkage, and DNA breakdown. The activation of some enzymes, such as the caspase family, is closely linked to apoptosis ( Samsuzzaman and Jang, 2022 ). In addition, mitogen-activated protein kinases (MAPKs) play an important role in activating apoptosis in HSCs ( Lee et al ., 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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Anti-Fibrotic Effects of DL-Glyceraldehyde in Hepatic Stellate Cells via Activation of ERK-JNK-Caspase-3 Signaling Axis

Samsuzzaman

Kim

2023

Biomol Ther (Seoul)

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During liver injury, hepatic stellate cells can differentiate into myofibroblast-like structures, which are more susceptible to proliferation, migration, and extracellular matrix generation, leading to liver fibrosis. Anaerobic glycolysis is associated with activated stellate cells and glyceraldehyde (GA) is an inhibitor of glucose metabolism. Therefore, this study aimed to investigate the anti-fibrotic effects of GA in human stellate LX-2 cells. In this study, we used cell viability, morphological analysis, fluorescence-activated cell sorting (FACS), western blotting, and qRT-PCR techniques to elucidate the molecular mechanism underlying the anti-fibrotic effects of GA in LX-2 cells. The results showed that GA significantly reduced cell density and inhibited cell proliferation and lactate levels in LX-2 cells but not in Hep-G2 cells. We found that GA prominently increased the activation of caspase-3/9 for apoptosis induction, and a pan-caspase inhibitor, Z-VAD-fmk, attenuated the cell death and apoptosis effects of GA, suggesting caspasedependent cell death. Moreover, GA strongly elevated reactive oxygen species (ROS) production and notably increased the phosphorylation of ERK and JNK. Interestingly, it dramatically reduced α-SMA and collagen type I protein and mRNA expression levels in LX-2 cells. Thus, inhibition of ERK and JNK activation significantly rescued GA-induced cell growth suppression and apoptosis in LX-2 cells. Collectively, the current study provides important information demonstrating the anti-fibrotic effects of GA, a glycolytic metabolite, and demonstrates the therapeutic potency of metabolic factors in liver fibrosis.

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Phytochemical‐mediated modulation of autophagy and endoplasmic reticulum stress as a cancer therapeutic approach

Al Azzani,

Nizami,

Magramane

et al. 2024

Phytotherapy Research

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Autophagy and endoplasmic reticulum (ER) stress are conserved processes that generally promote survival, but can induce cell death when physiological thresholds are crossed. The pro‐survival aspects of these processes are exploited by cancer cells for tumor development and progression. Therefore, anticancer drugs targeting autophagy or ER stress to induce cell death and/or block the pro‐survival aspects are being investigated extensively. Consistently, several phytochemicals have been reported to exert their anticancer effects by modulating autophagy and/or ER stress. Various phytochemicals (e.g., celastrol, curcumin, emodin, resveratrol, among others) activate the unfolded protein response to induce ER stress‐mediated apoptosis through different pathways. Similarly, various phytochemicals induce autophagy through different mechanisms (namely mechanistic target of Rapamycin [mTOR] inhibition). However, phytochemical‐induced autophagy can function either as a cytoprotective mechanism or as programmed cell death type II. Interestingly, at times, the same phytochemical (e.g., 6‐gingerol, emodin, shikonin, among others) can induce cytoprotective autophagy or programmed cell death type II depending on cellular contexts, such as cancer type. Although there is well‐documented mechanistic interplay between autophagy and ER stress, only a one‐way modulation was noted with some phytochemicals (carnosol, capsaicin, cryptotanshinone, guangsangon E, kaempferol, and δ‐tocotrienol): ER stress‐dependent autophagy. Plant extracts are sources of potent phytochemicals and while numerous phytochemicals have been investigated in preclinical and clinical studies, the search for novel phytochemicals with anticancer effects is ongoing from plant extracts used in traditional medicine (e.g., Origanum majorana). Nonetheless, the clinical translation of phytochemicals, a promising avenue for cancer therapeutics, is hindered by several limitations that need to be addressed in future studies.

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Growth-Suppressive and Apoptosis-Inducing Effects of Tetrandrine in SW872 Human Malignant Liposarcoma Cells via Activation of Caspase-9, Down-Regulation of XIAP and STAT-3, and ER Stress

Cited by 4 publications

References 46 publications

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

NDRG2 alleviates photoreceptor apoptosis by regulating the STAT3/TIMP3/MMP pathway in mice with retinal degenerative disease

Anti-Fibrotic Effects of DL-Glyceraldehyde in Hepatic Stellate Cells via Activation of ERK-JNK-Caspase-3 Signaling Axis

Phytochemical‐mediated modulation of autophagy and endoplasmic reticulum stress as a cancer therapeutic approach

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