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Characterization of a conjugated polysuccinimide-carboplatin compound
이선영,채장훈,Miklós Zrínyi,Xiangguo Che,최제용,조동휴 대한약리학회 2023 The Korean Journal of Physiology & Pharmacology Vol.27 No.1
Carboplatin, an advanced anticancer drug with excellent efficacy against ovarian cancer, was developed to alleviate the side effects that often occur with cisplatin and other platinum-based compounds. Our study reports the in vitro characteristics, viability, and activity of cells expressing the inducible nitric oxide synthase (iNOS) gene after carboplatin was conjugated with polysuccinimide (PSI) and administered in combination with other widely used anticancer drugs. PSI, which has promising properties as a drug delivery material, could provide a platform for prolonging carboplatin release, regulating its dosage, and improving its side effects. The iNOS gene has been shown to play an important role in both cancer cell survival and inhibition. Herein, we synthesized a PSI-carboplatin conjugate to create a modified anticancer agent and confirmed its successful conjugation. To ensure its solubility in water, we further modified the structure of the PSI-carboplatin conjugate with 2-aminoethanol groups. To validate its biological characteristics, the ovarian cancer cell line SKOV-3 and normal ovarian Chinese hamster ovary cells were treated with the PSI-carboplatin conjugate alone and in combination with paclitaxel and topotecan, both of which are used in conventional chemotherapy. Notably, PSI-carboplatin conjugation can be used to predict changes in the genes involved in cancer growth and inhibition. In conclusion, combination treatment with the newly synthesized polymer-carboplatin conjugate and paclitaxel displayed anticancer activity against ovarian cancer cells but was not toxic to normal ovarian cancer cells, resulting in the development of an effective candidate anticancer drug without severe side effects
Jeong Hannah,Kim Jwa-Young,Che Xiangguo,Choi Je-Yong,Jang Insan,Kim Seong-Gon 대한치과교정학회 2023 대한치과교정학회지 Vol.53 No.6
Objective: To investigate the long-term effects of 4-hexylresorcinol (4HR) on facial skeletal growth in growing male rats, with a focus on diabetic animal models. Methods: Forty male rats were used. Of them, type 1 diabetes mellitus was induced in 20 animals by administering 40 mg/kg streptozotocin (STZ), and they were assigned to either the STZ or 4HR-injected group (STZ/4HR group). The remaining 20 healthy rats were divided into control and 4HR groups. We administered 4HR subcutaneously at a weekly dose of 10 mg/kg until the rats were euthanized. At 16 weeks of age, whole blood was collected, and micro-computed tomography of the skull and femur was performed. Results: All craniofacial linear measurements were smaller in the STZ group than in the control group. The mandibular molar width was significantly smaller in the 4HR group than in the control group (P = 0.031) but larger in the STZ/4HR group than in the STZ group (P = 0.011). Among the diabetic animals, the STZ/4HR group exhibited significantly greater cortical bone thickness, bone mineral density, and bone volume than the STZ group. Serum testosterone levels were also significantly higher in the STZ/4HR group than in the STZ group. Conclusions: 4HR administration may have divergent effects on mandibular growth and bone mass in healthy and diabetic rats. In the context of diabetes, 4HR appears to have beneficial effects, potentially through the modulation of mitochondrial respiration.
Core Binding Factor β of Osteoblasts Maintains Cortical Bone Mass Via Stabilization of Runx2 in Mice
Lim, Kyung-Eun,Park, Na-Rae,Che, Xiangguo,Han, Min-Su,Jeong, Jae-Hwan,Kim, Shin-Yoon,Park, Clara Yongjoo,Akiyama, Haruhiko,Kim, Jung-Eun,Ryoo, Hyun-Mo,Stein, Janet L,Lian, Jane B,Stein, Gary S,Choi, J Wiley (John WileySons) 2015 Journal of bone and mineral research Vol.30 No.10
( Hyun-ju Kim ),( Hye-jin Yoon ),( Dong-kyo Lee ),( Xian Jin ),( Xiangguo Che ),( Je-yong Choi ) 생화학분자생물학회(구 한국생화학분자생물학회) 2021 BMB Reports Vol.54 No.5
Estrogen-related receptor γ (ERRγ), a member of the orphan nuclear receptor family, is a key mediator in cellular metabolic processes and energy homeostasis. Therefore, ERRγ has become an attractive target for treating diverse metabolic disorders. We recently reported that ERRγ acts as a negative regulator of osteoclastogenesis induced by receptor activator of nuclear factor-κB ligand (RANKL). In the present study, we explored the effects of an ERRγ-specific modulator, GSK5182, on ERRγ-regulated osteoclast differentiation and survival. Interestingly, GSK5182 increased ERRγ protein levels much as does GSK4716, which is an ERRγ agonist. GSK5182 inhibited osteoclast generation from bone-marrow-derived macrophages without affecting cytotoxicity. GSK5182 also attenuated RANKL-mediated expression of c- Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), pivotal transcription factors for osteoclastogenesis. Arrested osteoclast differentiation was associated with reduced RANK expression, but not with the M-CSF receptor, c-Fms. GSK5182 strongly blocked the phosphorylation of IκBα, c-Jun N-terminal kinase, and extracellular signal-regulated kinase in response to RANKL. GSK5182 also suppressed NF-κB promoter activity in a dose-dependent manner. In addition to osteoclastogenesis, GSK5182 accelerated osteoclast apoptosis by caspase-3 activation. Together, these results suggest that GSK5182, a synthetic ERRγ modulator, may have potential in treating disorders related to bone resorption. [BMB Reports 2021; 54(5): 266-271]
Kim, Hyun-Ju,Lee, Dong-Kyo,Jin, Xian,Che, Xiangguo,Choi, Je-Yong Korean Society for Molecular and Cellular Biology 2020 Molecules and cells Vol.43 No.4
Oleoylethanolamide (OEA), a bioactive lipid in bone, is known as an endogenous ligand for G protein-coupled receptor 119 (GPR119). Here, we explored the effects of OEA on osteoclast differentiation, function, and survival. While OEA inhibits osteoclast resorptive function by disrupting actin cytoskeleton, it does not affect receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation. OEA attenuates osteoclast spreading, blocks actin ring formation, and eventually impairs bone resorption. Mechanistically, OEA inhibits Rac activation in response to macrophage colony-stimulating factor (M-CSF), but not RANKL. Furthermore, the OEA-mediated cytoskeletal disorganization is abrogated by GPR119 knockdown using small hairpin RNA (shRNA), indicating that GPR119 is pivotal for osteoclast cytoskeletal organization. In addition, OEA induces apoptosis in both control and GPR119 shRNA-transduced osteoclasts, suggesting that GPR119 is not required for osteoclast apoptosis. Collectively, our findings reveal that OEA has inhibitory effects on osteoclast function and survival of mature osteoclasts via GPR119-dependent and GPR119-independent pathways, respectively.
Kim Hyun-Ju,Lee Dong-Kyo,Jin Xian,Che Xiangguo,Ryu Sung Ho,Choi Je-Yong 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Phospholipase D2 (PLD2), a signaling protein, plays a central role in cellular communication and various biological processes. Here, we show that PLD2 contributes to bone homeostasis by regulating bone resorption through osteoclastic cell migration and microtubule-dependent cytoskeletal organization. Pld2-deficient mice exhibited a low bone mass attributed to increased osteoclast function without altered osteoblast activity. While Pld2 deficiency did not affect osteoclast differentiation, its absence promoted the migration of osteoclast lineage cells through a mechanism involving M-CSF-induced activation of the PI3K–Akt–GSK3β signaling pathway. The absence of Pld2 also boosted osteoclast spreading and actin ring formation, resulting in elevated bone resorption. Furthermore, Pld2 deletion increased microtubule acetylation and stability, which were later restored by treatment with a specific inhibitor of Akt, an essential molecule for microtubule stabilization and osteoclast bone resorption activity. Interestingly, PLD2 interacted with the M-CSF receptor (c-Fms) and PI3K, and the association between PLD2 and c-Fms was reduced in response to M-CSF. Altogether, our findings indicate that PLD2 regulates bone homeostasis by modulating osteoclastic cell migration and microtubule stability via the M-CSF-dependent PI3K–Akt–GSK3β axis.