Category: 347174-05-4

Suzuki-Karasaki, Manami; Ando, Takashi; Ochiai, Yushi; Kawahara, Kenta; Suzuki-Karasaki, Miki; Nakayama, Hideki; Suzuki-Karasaki, Yoshihiro published the artcile< Air Plasma-Activated Medium Evokes a Death-Associated Perinuclear Mitochondrial Clustering>, Safety of Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is air plasma activated medium perinuclear mitochondrial clustering; ROS; cancer; cell death; lipid peroxidation; mitochondrial network; mitochondrial positioning; perinuclear mitochondrial clustering; plasma-activated medium.

Intractable cancers such as osteosarcoma (OS) and oral cancer (OC) are highly refractory, recurrent, and metastatic once developed, and their prognosis is still disappointing. Tumor-targeted therapy, which eliminates cancers effectively and safely, is the current clin. choice. Since aggressive tumors are substantially resistant to multidisciplinary therapies that target apoptosis, tumor-specific activation of another cell death modality is a promising avenue for meeting this goal. Here, we report that a cold atm. air plasma-activated medium (APAM) can kill OS and OC by causing a unique mitochondrial clustering. This event was named monopolar perinuclear mitochondrial clustering (MPMC) based on its characteristic unipolar mitochondrial perinuclear accumulation. The APAM caused apoptotic and nonapoptotic cell death. The APAM increased mitochondrial ROS (mROS) and cell death, and the antioxidants such as N-acetylcysteine (NAC) prevented them. MPMC occurred following mitochondrial fragmentation, which coincided with nuclear damages. MPMC was accompanied by mitochondrial lipid peroxide (mLPO) accumulation and prevented by NAC, Ferrostatin-1, and Nocodazole. In contrast, the APAM induced minimal cell death, mROS generation, mLPO accumulation, and MPMC in fibroblasts. These results suggest that MPMC occurs in a tumor-specific manner via mitochondrial oxidative stress and microtubule-driven mitochondrial motility. MPMC induction might serve as a promising target for exerting tumor-specific cytotoxicity.

International Journal of Molecular Sciences published new progress about Air (plasma-activated medium). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Safety of Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Kitabayashi, Nanako; Nakao, Shohei; Mita, Yuichiro; Arisawa, Kotoko; Hoshi, Takayuki; Toyama, Takashi; Ishii, Kiyo-aki; Takamura, Toshinari; Noguchi, Noriko; Saito, Yoshiro published the artcile< Role of selenoprotein P expression in the function of pancreatic å°?cells: Prevention of ferroptosis-like cell death and stress-induced nascent granule degradation>, Product Details of C15H22N2O2, the main research area is pancreatic beta cells ferroptosis cell death; Ferroptosis; GPX4; Pancreatic å°?cells; Selenoprotein K; Selenoprotein P; Stress-induced nascent granule degradation (SINGD).

Selenoprotein P (SELENOP) is a major selenium (Se)-containing protein (selenoprotein) in human plasma that is mainly synthesized in the liver. SELENOP transports Se to the cells, while SELENOP synthesized in peripheral tissues is incorporated in a paracrine/autocrine manner to maintain the levels of cellular selenoproteins, called the SELENOP cycle. Pancreatic å°?cells, responsible for the synthesis and secretion of insulin, are known to express SELENOP. Here, using MIN6 cells as a mouse model for pancreatic å°?cells and Selenop small interfering (si)RNA, we found that Selenop gene knockdown (KD) resulted in decreased cell viability, cellular pro/insulin levels, insulin secretion, and levels of several cellular selenoproteins, including glutathione peroxidase 4 (Gpx4) and selenoprotein K (Selenok). These dysfunctions induced by Selenop siRNA were recovered by the addition of Se. Ferroptosis-like cell death, regulated by Gpx4, was involved in the decrease of cell viability by Selenop KD, while stress-induced nascent granule degradation (SINGD), regulated by Selenok, was responsible for the decrease in proinsulin. SINGD was also observed in the pancreatic å°?cells of Selenop knockout mice. These findings indicate a significant role of SELENOP expression for the function of pancreatic å°?cells by maintaining the levels of cellular selenoproteins such as GPX4 and SELENOK.

Free Radical Biology & Medicine published new progress about Antioxidants. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Product Details of C15H22N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Byun, Jun-Kyu; Lee, Seunghyeong; Kang, Gil Won; Lee, Yu Rim; Park, Soo Young; Song, Im-Sook; Yun, Jae Won; Lee, Jaebon; Choi, Yeon-Kyung; Park, Keun-Gyu published the artcile< Macropinocytosis is an alternative pathway of cysteine acquisition and mitigates sorafenib-induced ferroptosis in hepatocellular carcinoma>, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is sorafenib anticancer cysteine acquisition macropinocytosis ferroptosis hepatocellular carcinoma; Ferroptosis; Hepatocellular carcinoma; Macropinocytosis; Sorafenib; Sorafenib resistance.

Macropinocytosis, an important nutrient-scavenging pathway in certain cancer cells, allows cells to compensate for intracellular amino acid deficiency under nutrient-poor conditions. Ferroptosis caused by cysteine depletion plays a pivotal role in sorafenib responses during hepatocellular carcinoma (HCC) therapy. However, it is not known whether macropinocytosis functions as an alternative pathway to acquire cysteine in sorafenib-treated HCC, and whether it subsequently mitigates sorafenib-induced ferroptosis. This study aimed to investigate whether sorafenib drives macropinocytosis induction, and how macropinocytosis confers ferroptosis resistance on HCC cells. Macropinocytosis, both in HCC cells and HCC tissues, was evaluated by measuring TMR-dextran uptake or lysosomal degradation of DQ-BSA, and ferroptosis was evaluated via C11-BODIPY fluorescence and 4-HNE staining. Sorafenib-induced ferroptosis and macropinocytosis were validated in tumor tissues taken from HCC patients who underwent ultrasound-guided needle biopsy. Sorafenib increased macropinocytosis in human HCC specimens and xenografted HCC tissues. Sorafenib-induced mitochondrial dysfunction was responsible for activation of PI3K-RAC1-PAK1 signaling, and amplified macropinocytosis in HCC. Importantly, macropinocytosis prevented sorafenib-induced ferroptosis by replenishing intracellular cysteine that was depleted by sorafenib treatment; this rendered HCC cells resistant to sorafenib. Finally, inhibition of macropinocytosis by amiloride markedly enhanced the anti-tumor effect of sorafenib, and sensitized resistant tumors to sorafenib. In summary, sorafenib induced macropinocytosis, which conferred drug resistance by mitigating sorafenib-induced ferroptosis. Thus, targeting macropinocytosis is a promising therapeutic strategy to facilitate ferroptosis-based therapy for HCC.

Journal of Experimental & Clinical Cancer Research published new progress about Cell division control protein 42 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Recommanded Product: Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Zhang, Hongbo; Zhuo, Yuzhen; Li, Dihua; Zhang, Lanqiu; Gao, Qiaoying; Yang, Lei; Yuan, Xiangfei published the artcile< Dihydroartemisinin inhibits the growth of pancreatic cells by inducing ferroptosis and activating antitumor immunity>, SDS of cas: 347174-05-4, the main research area is dihydroartemisinin pancreas cell growth ferroptosis antitumor immunity; Dihydroartemisinin; Ferroptosis; M2; MDSCs; NK; NKT; Pancreatic cancer.

Dihydroartemisinin (DHA) exhibits a direct antitumor effect in various tumor models. However, the mechanism of DHA inducing ferroptosis and activating antitumor immunity remains obscure. Therefore, our study was dedicated to investigate the effect of DHA on ferroptosis and tumor microenvironment and elucidate the underlying mol. mechanism. PDAC orthotopic tumor model was used to investigate tumor proliferation and the population of immune cell in vivo, including M2-type macrophages (M2), myeloid-derived suppressor cells (MDSCs), CD4+T cells, CD8+T cells, NK cells and NKT cells. Levels of GPX4, SLC7A11, P53 and ALOX12 were determined by Real-time PCR and Western blot. CCK8 assay was performed to detect cell viability, and the ferroptosis was distinguished by flow cytometry. Our results showed that DHA inhibited pancreatic cancer cell proliferation. In addition, DHA induced cell ferroptosis by up-regulating the expression of P53 and ALOX12, which was blocked by baicalein (a selective ALOX12 inhibitor). However, DHA also up-regulated the expression of GPX4 and SLC7A11. On the other hand, DHA significantly decreased the suppressive expansion of M2 and MDSCs. Moreover, DHA increased the immune cell population of CD8+T cells, NK cells and NKT cells in the tumor tissues of the tumor-bearing mice. Whereas, the DHA treatment did not affect the frequencies of M2, MDSCs, CD4+T, CD8+T, NK and NKT cells in the spleen. Our research provided exptl. evidences on the activity and mechanism of ferroptosis induced by DHA and revealed that DHA regulated tumor local immunosuppressive microenvironment.

European Journal of Pharmacology published new progress about CD4-positive T cell. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, SDS of cas: 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Jo, Ara; Bae, Jin Hee; Yoon, Yu Jeong; Chung, Tae Hun; Lee, Eun-Woo; Kim, Young-Ho; Joh, Hea Min; Chung, Jin Woong published the artcile< Plasma-activated medium induces ferroptosis by depleting FSP1 in human lung cancer cells>, Related Products of 347174-05-4, the main research area is FSP1 ferroptosis anticancer agent lung cancer.

Cold atm. plasma (CAP) that generates reactive oxygen species (ROS) has received considerable scientific attentions as a new type of anticancer. In particular, an indirect treatment method of inducing cancer cell death through plasma-activated medium (PAM), rather than direct plasma treatment has been well established. Although various cell death pathways such as apoptosis, necroptosis, and autophagy have been suggested to be involved in PAM-induced cell death, the involvement of ferroptosis, another type of cell death regulated by lipid ROS is largely unknown. This study reports, that PAM promotes cell death via ferroptosis in human lung cancer cells, and PAM increases intracellular and lipid ROS, thereby resulting in mitochondrial dysfunction. The treatment of cells with N-acetylcysteine, an ROS scavenging agent, or ferrostatin-1, a ferroptosis inhibitor, protects cells against PAM-induced cell death. Interestingly, ferroptosis suppressor protein 1 (FSP1) is downregulated upon PAM treatment. Furthermore, the treatment of cells with iFSP1, an inhibitor of FSP1, further enhances PAM-induced ferroptosis. Finally, this study demonstrates that PAM inhibits tumor growth in a xenograft model with an increase in 4-hydroxynoneal and PTGS2, a byproduct of lipid peroxidation, and a decrease in FSP1 expression. This study will provide new insights into the underlying mechanism and therapeutic strategies of PAM-mediated cancer treatment.

Cell Death & Disease published new progress about Animal gene Role: BSU (Biological Study, Unclassified), PRP (Properties), BIOL (Biological Study) (NCOA7). 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Related Products of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Wang, Kai; Jiang, Li; Zhong, Yueyang; Zhang, Yin; Yin, Qichuan; Li, Su; Zhang, Xiaobo; Han, Haijie; Yao, Ke published the artcile< Ferrostatin-1-loaded liposome for treatment of corneal alkali burn via targeting ferroptosis>, Safety of Ethyl 3-amino-4-(cyclohexylamino)benzoate, the main research area is ferrostatin liposome treatment corneal alkali burn targeting ferroptosis; corneal alkali burn; corneal neovascularization; ferroptosis; ferrostatin‐1; liposome.

Alkali burn is a potentially blinding corneal injury. During the progression of alkali burn-induced injury, overwhelmed oxidative stress in the cornea triggers cell damage, including oxidative changes in cellular macromols. and lipid peroxidation in membranes, leading to impaired corneal transparency, decreased vision, or even blindness. In this study, we identified that ferroptosis, a type of lipid peroxidation-dependent cell death, mediated alkali burn-induced corneal injury. Ferroptosis-targeting therapy protected the cornea from cell damage and neovascularization. However, the specific ferroptosis inhibitor ferrostatin-1 (Fer-1) is hydrophobic and cannot be directly applied in the clinic. Therefore, we developed Fer-1-loaded liposomes (Fer-1-NPs) to improve the bioavailability of Fer-1. Our study demonstrated that Fer-1-NPs exerted remarkable curative effects regarding corneal opacity and neovascularization in vivo. The efficacy was comparable to that of dexamethasone, but without appreciable side effects. The significant suppression of ferroptosis (induced by lipid peroxidation and mitochondria disruption), inflammation, and neovascularization might be the mechanisms underlying the therapeutic effect of Fer-1-NPs. Moreover, the Fer-1-NPs treatment showed no signs of cytotoxicity, hematol. toxicity, or visceral organ damage, which further confirmed the biocompatibility. Overall, Fer-1-NPs provide a new prospect for safe and effective therapy for corneal alkali burn.

Bioengineering & Translational Medicine published new progress about Bioavailability. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Safety of Ethyl 3-amino-4-(cyclohexylamino)benzoate.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Yin, Jiameng; Lin, Yajun; Fang, Weiwei; Zhang, Xin; Wei, Jie; Hu, Gang; Liu, Pu; Niu, Jie; Guo, Jun; Zhen, Yongzhan; Li, Jian published the artcile< Tetrandrine citrate suppresses breast cancer via depletion of glutathione peroxidase 4 and activation of nuclear receptor coactivator 4-mediated ferritinophagy>, Application In Synthesis of 347174-05-4, the main research area is tetrandrine citrate glutathione peroxidase nuclear receptor coactivator breast cancer; breast cancer; ferroptosis; glutathione peroxidase 4; nuclear receptor coactivator 4; tetrandrine citrate.

Tetrandrine citrate (TetC), a novel tetrandrine salt with high water solubility, demonstrates a potent antitumor activity in chronic myeloid leukemia. Studies have indicated an important role of ferroptosis in breast cancer (BC). However, whether TetC inhibits BC progression via ferroptosis has never been explored. In the present study, we showed that TetC had a significant inhibitory effect on the proliferation and migration of MCF7 and MDA-MB-231 cells. Then, we combined TetC with different inhibitors to determine which form of cell death could be driven by TetC. MTT assay showed that ferrostatin (Fer-1) demonstrated the most potent effect on improving TetC-induced cell death in contrast to other inhibitors. TetC was also shown to significantly increase the mRNA level of prostaglandinendoperoxide synthase 2 (Ptgs2), a ferroptosis marker. Further studies showed that TetC significantly suppressed the expression of glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) but increased the expression of nuclear receptor coactivator 4 (NCOA4) in MCF7 and MDA-MB-231 cells even in the presence of erastin or Ras-selective lethal 3 (RSL3). Collectively, we showed novel data that ferroptosis was a major form of TetC-induced cell death. Moreover, TetC-induced ferroptotic cell death was achieved via suppressing GPX4 expression and activating NCOA4-mediated ferritinophagy in BC cells.

Frontiers in Pharmacology published new progress about Autophagosome. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Application In Synthesis of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Liang, Nan-Nan; Zhao, Ying; Guo, Yue-Yue; Zhang, Zhi-Hui; Gao, Lan; Yu, De-Xin; Xu, De-Xiang; Xu, Shen published the artcile< Mitochondria-derived reactive oxygen species are involved in renal cell ferroptosis during lipopolysaccharide-induced acute kidney injury>, Synthetic Route of 347174-05-4, the main research area is mitochondria reactive oxygen species ferroptosis lipopolysaccharide acute kidney injury; Acute kidney injury; Ferroptosis; Mitochondria-derived reactive oxygen species; Mitochondria-targeted antioxidants.

Our earlier studies indicated that reactive oxygen species (ROS) were involved in lipopolysaccharide (LPS)-induced acute kidney injury (AKI). The present study aimed to explore the role of mitochondria-derived ROS on renal cell ferroptosis during LPS-induced AKI. Male CD-1 mice were i.p. injected with LPS (2.0 mg/kg). Renal MDA and 4HNE residue, two markers of lipid peroxidation, were increased in LPS-exposed mice. Oxidized lipids were detected in LPS-treated human HK-2 cells. In vivo, ferroptosis-characteristic ultrastructure changes, including cell volume reduction, nuclear pyknosis and smaller mitochondria, were shown in renal cortex. In vitro, abnormal alteration of mitochondrial membrane potential was observed in LPS-treated human HK-2 cells. Ferrostatin-1, a specific inhibitor of ferroptosis, attenuated LPS-evoked renal lipid peroxidation, ferroptosis-characteristic mitochondrial damage and renal cell death. Mechanistically, mitochondria-derived ROS were elevated in LPS-stimulated HK-2 cells. MitoQ, a mitochondria-targeted antioxidant, almost completely scavenged LPS-stimulated mitochondrial ROS in human HK-2 cells. Moreover, pretreatment with MitoQ attenuated LPS-induced GSH depletion and lipid peroxidation in mouse kidney. Finally, pretreatment with MitoQ alleviated LPS-induced renal cell death and AKI. Taken together, these results suggest that mitochondria-derived ROS contribute, at least partially, to renal cell ferroptosis during LPS-induced AKI. Mitochondria-targeted antioxidants may be potential therapeutic agents for sepsis-induced AKI.

International Immunopharmacology published new progress about Acute kidney injury. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Synthetic Route of 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Feng, Zhuan; Qin, Yifei; Huo, Fei; Jian, Zhe; Li, Xiaomin; Geng, Jiejie; Li, Yong; Wu, Jiao published the artcile< NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation induced skin injury>, Product Details of C15H22N2O2, the main research area is skin injury GSH GPX4 NMN ferroptosis; Ferroptosis; NMN; Skin injury.

Oxidative stress and lipid peroxidation are major causes of skin injury induced by UV irradiation Ferroptosis is a form of regulated necrosis driven by iron-dependent peroxidation of phospholipids and contributes to kinds of tissue injuries. However, it remains unclear whether the accumulation of lipid peroxides in UV irradiation-induced skin injury could lead to ferroptosis. We generated UV irradiation-induced skin injury mice model to examine the accumulation of the lipid peroxides and iron. Lipid peroxides 4-HNE, the oxidative enzyme COX2, the oxidative DNA damage biomarker 8-OHdG, and the iron level were increased in UV irradiation-induced skin. The accumulation of iron and lipid peroxidation was also observed in UVB-irradiated epidermal keratinocytes without actual ongoing ferroptotic cell death. Ferroptosis was triggered in UV-irradiated keratinocytes stimulated with ferric ammonium citrate (FAC) to mimic the iron overload. Although GPX4 protected UVB-injured keratinocytes against ferroptotic cell death resulted from dysregulation of iron metabolism and the subsequent increase of lipid ROS, keratinocytes enduring constant UVB treatment were markedly sensitized to ferroptosis. NMN (NMN) which is a direct and potent NAD+ precursor supplement, rescued the imbalanced NAD+/NADH ratio, recruited the production of GSH and promoted resistance to lipid peroxidation in a GPX4-dependent manner. Taken together, our data suggest that NMN recruits GSH to enhance GPX4-mediated ferroptosis defense in UV irradiation-induced skin injury and inhibits oxidative skin damage. NMN or ferroptosis inhibitor might become promising therapeutic approaches for treating oxidative stress-induced skin diseases or disorders.

Biochimica et Biophysica Acta, Molecular Basis of Disease published new progress about Antioxidants. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, Product Details of C15H22N2O2.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics

Chen, Kang-Ni; Guan, Qi-Wen; Yin, Xi-Xi; Wang, Zhao-Jun; Zhou, Hong-Hao; Mao, Xiao-Yuan published the artcile< Ferrostatin-1 obviates seizures and associated cognitive deficits in ferric chloride-induced posttraumatic epilepsy via suppressing ferroptosis>, SDS of cas: 347174-05-4, the main research area is cognitive deficit posttraumatic epilepsy ferroptosis seizure ferrostatin 1; Cognitive impairment; Ferroptosis; Ferrostatin-1; Posttraumatic epilepsy; Seizure; Therapy.

Posttraumatic epilepsy (PTE) is a prevalent complication of brain trauma. Current anti-epileptic drugs available do not have satisfactory response to PTE. It is of desperate need to explore novel therapeutic approaches for curing PTE. Our prior work revealed that ferroptosis, a recently discovered mode of cell death, occurs in rodent model of PTE. In the present study, we aimed to further investigate the effect of ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor, on seizure behavior and cognitive deficit in a mouse model of PTE. The preparation of PTE was performed by stereotaxical injection in the somatosensory cortex region of 50 mM FeCl3. Seizure activity was assessed via Racine scoring and EEG anal. PTE-related cognitive function was evaluated by novel object recognition and Morris water maze tests. Ferroptosis-related indexes including glutathione peroxidase (GPx) activity and protein expressions of 4-hydroxynonenal (4-HNE) were detected using a com. kit and immunofluorescence, resp. It was found that treatment with Fer-1 significantly exerted protective effects against acute seizure and memory decline, although no evident effect on epileptic progression. Fer-1 also exhibited good tolerability and safety as we observed that it hardly influenced the body weight Furthermore, it was noted that administration of Fer-1 suppressed ferroptosis-related indexes including GPx activity and protein expressions of 4-HNE in hippocampus. These data altogether indicate that Fer-1 has potent therapeutic effects against seizures and cognitive impairment following PTE-induced brain insult. Fer-1 may act as a promising drug for curing PTE patients.

Free Radical Biology & Medicine published new progress about Anticonvulsants. 347174-05-4 belongs to class esters-buliding-blocks, and the molecular formula is C15H22N2O2, SDS of cas: 347174-05-4.

Referemce:
Ester – Wikipedia,
Ester – an overview | ScienceDirect Topics