Effect of treatment period with LC478, a disubstituted adamantayl derivative, on P-glycoprotein inhibition: its application to increase docetaxel absorption in rats

Han, Sang-Hoon; Kim, Eun Sun; You, Byoung Hoon; Chae, Hee‐Sung; Lu, Qili; Chin, Young‐Won; Ahn, Hee‐Chul; Chung, Suk‐Jae; Lee, Kyeong; Choi, Young Hee

doi:10.1080/00498254.2019.1700318

Cited by 3 publications

(1 citation statement)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, LW6, a well-designated HIF-1α inhibitor, was discovered as a potent inhibitor of BCRP, thereby preventing resistance to doxorubicin [ 135 ]. Similarly, LC478 inhibited the induction of P-gp, which resulted in an increased docetaxel absorption in a rat model of colorectal adenocarcinoma [ 136 ]. EZN-2208 (PEG-SN38) was found to overcome the ATP-binding cassette superfamily G member 2 (ABCG2)-mediated topotecan resistance by increasing the DNA damage repair in breast cancer 1 (BRCA1)-deficient mouse mammary tumors [ 137 , 138 ], while chetomin blocked the reprogramming of tumor metabolism in human malignant glioma cells to prevent hypoxic radioresistance [ 139 ].…”

Section: Roles Of Hif-1 In Anticancer Drug Resistance and Cancer-rela...mentioning

confidence: 99%

Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain

Bui

Nguyen

Lee

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

Hypoxia-inducible factor-1 (HIF-1) is a key transcription factor that regulates the transcription of many genes that are responsible for the adaptation and survival of tumor cells in hypoxic environments. Over the past few decades, tremendous efforts have been made to comprehensively understand the role of HIF-1 in tumor progression. Based on the pivotal roles of HIF-1 in tumor biology, many HIF-1 inhibitors interrupting expression, stabilization, DNA binding properties, or transcriptional activity have been identified as potential therapeutic agents for various cancers, yet none of these inhibitors have yet been successfully translated into clinically available cancer treatments. In this review, we briefly introduce the regulation of the HIF-1 pathway and summarize its roles in tumor cell proliferation, angiogenesis, and metastasis. In addition, we explore the implications of HIF-1 in the development of drug resistance and cancer-related pain: the most commonly encountered obstacles during conventional anticancer therapies. Finally, the current status of HIF-1 inhibitors in clinical trials and their perspectives are highlighted, along with their modes of action. This review provides new insights into novel anticancer drug development targeting HIF-1. HIF-1 inhibitors may be promising combinational therapeutic interventions to improve the efficacy of current cancer treatments and reduce drug resistance and cancer-related pain.

show abstract

Section: Roles Of Hif-1 In Anticancer Drug Resistance and Cancer-rela...mentioning

confidence: 99%

Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain

Bui

Nguyen

Lee

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

show abstract

Natural Coptidis Rhizoma Nanoparticles Improved the Oral Delivery of Docetaxel

Ye,

Ding,

Pan

et al. 2024

IJN

View full text Add to dashboard Cite

Purpose Docetaxel (DTX) is a valuable anti-tumor chemotherapy drug with limited oral bioavailability. This study aims to develop an effective oral delivery system for DTX using natural nanoparticles (Nnps) derived from Coptidis Rhizoma extract. Methods DTX-loaded self-assembled nanoparticles (Nnps-DTX) were created using an optimized heat-induction strategy. Nnps-DTX’s shape, size, Zeta potential, and in vitro stability were all carefully examined. Additionally, the study investigated the encapsulation efficiency, loading capacity, crystal form, and intermolecular interactions of DTX in Nnps-DTX. Subsequently, the solubility, release, cellular uptake, metabolic stability, and preclinical pharmacokinetics of DTX in Nnps-DTX were systematically evaluated. Finally, the cytotoxicity of Nnps-DTX was assessed in three tumor cell lines. Results Nnps-DTX was spherical in shape, 138.6 ± 8.2 nm in size, with a Zeta potential of −20.8 ± 0.6 mV, a DTX encapsulation efficiency of 77.6 ± 8.5%, and a DTX loading capacity of 6.8 ± 1.9%. Hydrogen bonds, hydrophobic interactions, and electrostatic interactions were involved in the formation of Nnps-DTX. DTX within Nnps-DTX was in an amorphous form, resulting in enhanced solubility (23.3 times) and release compared to free DTX. Following oral treatment, the mice in the Nnps-DTX group had DTX peak concentrations 8.8, 23.4, 44.6, and 5.7 times higher in their portal vein, systemic circulation, liver, and lungs than the mice in the DTX group. Experiments performed in Caco-2 cells demonstrated a significant increase in DTX uptake by Nnps-DTX compared to free DTX, which was significantly inhibited by indomethacin, an inhibitor of caveolae-mediated endocytosis. Furthermore, compared to DTX, DTX in Nnps-DTX demonstrated better metabolic stability in liver microsomes. Notably, Nnps-DTX significantly reduced the viability of MCF-7, HCT116, and HepG2 cells. Conclusion The novel self-assembled nanoparticles considerably enhanced the cellular absorption, solubility, release, metabolic stability, and pharmacokinetics of oral DTX and demonstrated strong cytotoxicity against tumor cell lines.

show abstract

Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy

Youssef,

Zhao,

Purcell

et al. 2024

Front. Oncol.

View full text Add to dashboard Cite

The SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) has emerged as a critical regulator in cancer biology, modulating the stability of Hypoxia-Inducible Factor 1-alpha (HIF1α) and influencing a network of hypoxia-driven pathways within the tumor microenvironment (TME). SMURF2 targets HIF1α for ubiquitination and subsequent proteasomal degradation, disrupting hypoxic responses that promote cancer cell survival, metabolic reprogramming, angiogenesis, and resistance to therapy. Beyond its role in HIF1α regulation, SMURF2 exerts extensive control over cellular processes central to tumor progression, including chromatin remodeling, DNA damage repair, ferroptosis, and cellular stress responses. Notably, SMURF2’s ability to promote ferroptotic cell death through GSTP1 degradation offers an alternative pathway to overcome apoptosis resistance, expanding therapeutic options for refractory cancers. This review delves into the multifaceted interactions between SMURF2 and HIF1α, emphasizing how their interplay impacts metabolic adaptations like the Warburg effect, immune evasion, and therapeutic resistance. We discuss SMURF2’s dual functionality as both a tumor suppressor and, in certain contexts, an oncogenic factor, underscoring its potential as a highly versatile therapeutic target. Furthermore, modulating the SMURF2-HIF1α axis presents an innovative approach to destabilize hypoxia-dependent pathways, sensitizing tumors to chemotherapy, radiotherapy, and immune-based treatments. However, the complexity of SMURF2’s interactions necessitate a thorough assessment of potential off-target effects and challenges in specificity, which must be addressed to optimize its clinical application. This review concludes by proposing future directions for research into the SMURF2-HIF1α pathway, aiming to refine targeted strategies that exploit this axis and address the adaptive mechanisms of aggressive tumors, ultimately advancing the landscape of precision oncology.

show abstract

Effect of treatment period with LC478, a disubstituted adamantayl derivative, on P-glycoprotein inhibition: its application to increase docetaxel absorption in rats

Cited by 3 publications

References 42 publications

Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain

Hypoxia-Inducible Factor-1: A Novel Therapeutic Target for the Management of Cancer, Drug Resistance, and Cancer-Related Pain

Natural Coptidis Rhizoma Nanoparticles Improved the Oral Delivery of Docetaxel

Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy

Contact Info

Product

Resources

About