Core‐Scaffold‐Inspired Asymmetric Synthesis of Polysubstituted Chiral Hexahydropyridazines that Potently Inhibit Breast Cancer Cell Proliferation by Inducing Apoptosis

Acne vulgaris is a prevalent cutaneous disease characterized by a multifactorial pathogenic process including hyperseborrhea, inflammation, over‐keratinization of follicular keratinocytes and Propionibacterium acnes (P acnes) overgrowth. Salicylic acid (SA), a beta‐hydroxy acid, is frequently used in the treatment of acne. SA has been found to decrease skin lipids and to possess anti‐inflammatory properties. However, few studies have elucidated the mechanisms and pathways involved in such treatment of acne. In this study, we initially investigated the anti‐acne properties of SA in human SEB‐1 sebocytes. Treatment with SA decreased sebocyte lipogenesis by downregulating the adenosine monophosphate‐activated protein kinase (AMPK)/sterol response element‐binding protein‐1 (SREBP‐1) pathway and reduced inflammation by suppressing the NF‐κB pathway in these cells. Salicylic acid also decreased the cell viability of SEB‐1 by increasing apoptosis via the death signal receptor pathway. Subsequently, histopathological analysis of a rabbit ear acne model after application of SA for three weeks confirmed that SA suppressed the levels of cytokines and major pathogenic proteins around acne lesions, which supports the mechanisms suggested by our in vitro experiments. These results initially clarified that therapeutic activities of SA in acne vulgaris treatment could be associated with the regulation of SREBP‐1 pathway and NF‐κB pathway in human SEB‐1 sebocytes.

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“…Real‐time PCR and Western blot analysis were performed according to our previous report . More information is provided in the “Data ”.…”

Section: Methodsmentioning

confidence: 99%

“…The experimental procedure of Nile red‐stained or TUNEL‐stained SEB‐1 cells, and the IHC‐stained skin tissue sections were stained according to our previous report . More information is provided in the “Data ”.…”

Section: Methodsmentioning

confidence: 99%

Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes

Jin

Cong

Wen

et al. 2019

Experimental Dermatology

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“…In order to assess the possibility of subroutine cell death underlying 8m treatment, flow cytometry with annexinV/PI dual staining was used to assess the activation of apoptosis [39][40][41][42][43][44][45] . Hoechst 33258 staining also clearly showed that nuclear morphological changes in apoptotic cells, including chromatin condensation and apoptotic bodies, mediated apoptosis ( Figure 5(D)).…”

Section: Novel Hsp90/pi3ka Dual Inhibitors 8m Suppressed Cell B16 Melmentioning

confidence: 99%

Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma

Qin

Wang

Jiang

et al. 2019

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…However, radiation resistance remains a major obstacle to successful treatment of advanced NPC. The detailed mechanism by which NPC develops radiation resistance and metastatic recurrence remains unclear [ 10 – 13 ]. Hence, the identification of novel prognostic biomarkers and therapeutic targets is urgently needed for NPC patients.…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA NEAT1 regulates epithelial membrane protein 2 expression to repress nasopharyngeal carcinoma migration and irradiation-resistance through miR-101-3p as a competing endogenous RNA mechanism

Wang

Chen

et al. 2017

Oncotarget

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The altered expression of long non-coding RNAs (lncRNAs) is often related to carcinogenesis, metastasis and resistance to radiation or chemotherapy. In the current study, cDNA microarray analysis found that NEAT1 expression was reduced in nasopharyngeal carcinoma (NPC) patients and that it regulated NPC progression. However, the detailed mechanisms of NEAT1 in NPC were unclear. NEAT1 repressed NPC cell growth, invasion and radiation resistance in vitro and tumor metastasis in vivo. In addition, the results of an approach integrating bioinformatics, luciferase reporter assays and RNA immunoprecipitation indicated that NEAT1 antagonized miR-101-3p through a competing endogenous RNA (ceRNA) mechanism and that the interaction between NEAT1 and EMP2 was miR-101-3p dependent. Our results showed a novel connection of NEAT1, miR-101-3p and EMP2 in NPC migration and radiation resistance.

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Core‐Scaffold‐Inspired Asymmetric Synthesis of Polysubstituted Chiral Hexahydropyridazines that Potently Inhibit Breast Cancer Cell Proliferation by Inducing Apoptosis

Cited by 21 publications

References 73 publications

Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes

Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes

Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma

Long non-coding RNA NEAT1 regulates epithelial membrane protein 2 expression to repress nasopharyngeal carcinoma migration and irradiation-resistance through miR-101-3p as a competing endogenous RNA mechanism

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