Trichostatin A Induces Autophagy in Cervical Cancer Cells by Regulating the PRMT5-STC1-TRPV6-JNK Pathway

Liu, Jian-Hao; Cao, Yanming; Rong, Zhi-Peng; Ding, Juan; Xi, Peng

doi:10.1159/000507937

Cited by 21 publications

(10 citation statements)

References 33 publications

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“…A great number of studies focus on the antiproliferative effects of trichostatin A as monotherapy on cervical cancer cell lines. Liu et al suggested that trichostatin A induces human cervical cancer cell apoptosis by decreasing DNA-methyltransferase 3B [ 34 ], while another study group treated the HeLa and CaSki cell lines with different concentrations of HDACI and discovered that trichostatin A significantly diminished cell viability, protein arginine methyltransferase 5 (PRMT5), transient receptor potential cation channel, subfamily V, member 6 (TRPV6), and p62, levels, but augmented the apoptosis rate, the LC3 II/I ratio and the beclin1, stanniocalcin 1 (STC1), and phosphorylated Jun N-terminal kinase (p-JNK), protein levels [ 35 ]. Furthermore, Ma et al identified the putative zinc transporter gene LIV1 as a key gene in the context of trichostatin A-mediated cervical cancer cell apoptosis induction [ 36 ], while Raju et al demonstrated that trichostatin A robustly induces Kallikrein-related peptidase 7 ( KLK7 ) mRNA expression and increases occupancy of specificity protein 1 (Sp1) at the proximal KLK7 promoter in HeLa cells [ 37 ].…”

Section: Hydroxamic Acidsmentioning

confidence: 99%

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy

Psilopatis

Garmpis

Garmpi

et al. 2023

Cancers

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Cervical carcinoma is one of the most common cancers among women globally. Histone deacetylase inhibitors (HDACIs) constitute anticancer drugs that, by increasing the histone acetylation level in various cell types, induce differentiation, cell cycle arrest, and apoptosis. The aim of the current review is to study the role of HDACIs in the treatment of cervical cancer. A literature review was conducted using the MEDLINE and LIVIVO databases with a view to identifying relevant studies. By employing the search terms “histone deacetylase” and “cervical cancer”, we managed to identify 95 studies published between 2001 and 2023. The present work embodies the most up-to-date, comprehensive review of the literature centering on the particular role of HDACIs as treatment agents for cervical cancer. Both well-established and novel HDACIs seem to represent modern, efficacious anticancer drugs, which, alone or in combination with other treatments, may successfully inhibit cervical cancer cell growth, induce cell cycle arrest, and provoke apoptosis. In summary, histone deacetylases seem to represent promising future treatment targets in cervical cancer.

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Section: Hydroxamic Acidsmentioning

confidence: 99%

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy

Psilopatis

Garmpis

Garmpi

et al. 2023

Cancers

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“…The PRMT5 axis is a novel transcriptional activation program. 8 The overexpression of PRMT5 dramatically increases TRPV levels, 20 and NOX4 affects TRPV1 activity in sensory nerves. 16 When considering that PTX-induced neuropathic pain is associated with TRPV1 upregulation in the lumbar DRG, 17 we subsequently investigated whether PTX-upregulated NOX4/PRMT5 signaling is associated with the transcriptional activation of TRPV1 in DRG neurons.…”

Section: Ptx-enhanced Nox4/prmt5 Pathway Modifies Trpv1 Transcription...mentioning

confidence: 99%

“…17 Notably, NOX4 contributes to PRMT5 expression in inflammatory disease, 18 and PTX-induced neuropathic pain is usually accompanied by neuroinflammation. 19 Additionally, the overexpression of PRMT5 can increase TRPV levels for apoptosis and autophagy, 20 which were associated with PTX-induced neuropathic pain. 21 Therefore, we hypothesized that NOX4 induces PRMT5-mediated H3R2me2s to increase H3K4me3 by recruiting WDR5, thus resulting in the upregulation of TRPV1 transcription in DRG of PTX-induced neuropathic pain.…”

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confidence: 99%

Protein Arginine Methyltransferase 5 Contributes to Paclitaxel-Induced Neuropathic Pain by Activating Transient Receptor Potential Vanilloid 1 Epigenetic Modification in Dorsal Root Ganglion

Yeh

Lai

Peng

et al. 2023

Anesthesia &Amp; Analgesia

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BACKGROUND: Paclitaxel (PTX), which is a first-line chemotherapy drug used to treat various types of cancers, exhibits peripheral neuropathy as a common side effect that is difficult to treat. Protein arginine methyltransferase 5 (PRMT 5) is a key regulator of the chemotherapy response, as chemotherapy drugs induce PRMT5 expression. However, little is known about the PRMT5-mediated epigenetic mechanisms involved in PTX-induced neuropathic allodynia. METHODS: Sprague–Dawley rats were intraperitoneally given PTX to induce neuropathic pain. Biochemical analyses were conducted to measure the protein expression levels in the dorsal root ganglion (DRG) of the animals. The von Frey test and hot plate test were used to evaluate nociceptive behaviors. RESULTS: PTX increased the PRMT5 (mean difference [MD]: 0.68, 95% confidence interval [CI], 0.88–0.48; P < .001 for vehicle)-mediated deposition of histone H3R2 dimethyl symmetric (H3R2me2s) at the transient receptor potential vanilloid 1 (Trpv1) promoter in the DRG. PRMT5-induced H3R2me2s recruited WD repeat domain 5 (WDR5) to increase trimethylation of lysine 4 on histone H3 (H3K4me3) at Trpv1 promoters, thus resulting in TRPV1 transcriptional activation (MD: 0.65, 95% CI, 0.82–0.49; P < .001 for vehicle) in DRG in PTX-induced neuropathic pain. Moreover, PTX increased the activity of NADPH oxidase 4 (NOX4) (MD: 0.66, 95% CI, 0.81–0.51; P < .001 for vehicle), PRMT5-induced H3R2me2s, and WDR5-mediated H3K4me3 in the DRG in PTX-induced neuropathic pain. Pharmacological antagonism and the selective knockdown of PRMT5 in DRG neurons completely blocked PRMT5-mediated H3R2me2s, WDR5-mediated H3K4me3, or TRPV1 expression and neuropathic pain development after PTX injection. Remarkably, NOX4 inhibition not only attenuated allodynia behavior and reversed the above-mentioned signaling but also reversed NOX4 upregulation via PTX. CONCLUSIONS: Thus, the NOX4/PRMT5-associated epigenetic mechanism in DRG has a dominant function in the transcriptional activation of TRPV1 in PTX-induced neuropathic pain.

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“…This team observed that TSA, an HDAC inhibitor, induced p21 WAF1/CIP1 expression in human cervical cancer (HeLa) cells, which is associated with the downregulation of c myc expression [ 79 ]. Interestingly, deeper insights were provided by Liu and colleagues [ 84 ] about the effects of TSA on cervical cancer development. The results showed that TSA suppressed the proliferation and induced apoptosis and autophagy in cervical cancer cells via the PRMT5/ STC1/TRPV6/JNK axis.…”

Section: Anticancer Activity Of Tsamentioning

confidence: 99%

Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review

et al. 2022

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Trichostatin A (TSA), a natural derivative of dienohydroxamic acid derived from a fungal metabolite, exhibits various biological activities. It exerts antidiabetic activity and reverses high glucose levels caused by the downregulation of brain-derived neurotrophic factor (BDNF) expression in Schwann cells, anti-inflammatory activity by suppressing the expression of various cytokines, and significant antioxidant activity by suppressing oxidative stress through multiple mechanisms. Most importantly, TSA exhibits potent inhibitory activity against different types of cancer through different pathways. The anticancer activity of TSA appeared in many in vitro and in vivo investigations that involved various cell lines and animal models. Indeed, TSA exhibits anticancer properties alone or in combination with other drugs used in chemotherapy. It induces sensitivity of some human cancers toward chemotherapeutical drugs. TSA also exhibits its action on epigenetic modulators involved in cell transformation, and therefore it is considered an epidrug candidate for cancer therapy. Accordingly, this work presents a comprehensive review of the most recent developments in utilizing this natural compound for the prevention, management, and treatment of various diseases, including cancer, along with the multiple mechanisms of action. In addition, this review summarizes the most recent and relevant literature that deals with the use of TSA as a therapeutic agent against various diseases, emphasizing its anticancer potential and the anticancer molecular mechanisms. Moreover, TSA has not been involved in toxicological effects on normal cells. Furthermore, this work highlights the potential utilization of TSA as a complementary or alternative medicine for preventing and treating cancer, alone or in combination with other anticancer drugs.

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Trichostatin A Induces Autophagy in Cervical Cancer Cells by Regulating the PRMT5-STC1-TRPV6-JNK Pathway

Cited by 21 publications

References 33 publications

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy

The Emerging Role of Histone Deacetylase Inhibitors in Cervical Cancer Therapy

Protein Arginine Methyltransferase 5 Contributes to Paclitaxel-Induced Neuropathic Pain by Activating Transient Receptor Potential Vanilloid 1 Epigenetic Modification in Dorsal Root Ganglion

Pharmacological Properties of Trichostatin A, Focusing on the Anticancer Potential: A Comprehensive Review

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