Lipid droplet formation induced by icaritin derivative IC2 promotes a combination strategy for cancer therapy DOI Creative Commons

Guosheng Wu,

Ying Liang, Qian Zhang

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 17, 2024

Abstract Background Lipid metabolism is crucial in cancer progression. droplets (LDs) generated cells can act as protective mechanisms through alleviating lipotoxicity under stress conditions. We previously developed IC2 from the Chinese medicine icaritin an inhibitor of stearoyl-CoA desaturase 1 (SCD1). has been shown to disrupt lipid and inhibits cell proliferation. However, impact on intracellular LDs potential targeting LD formation for combination therapy remain unexplored.Methods was analyzed with oil red O or BODIPY staining by microscopy. quantification normalized number. IC2-induced cellular responses were revealed transcriptional analysis, real-time PCR, immunoblotting. Mitochondrial functions assessed measuring ATP production oxygen consumption. The source studied using transporter inhibitors deprivation. effect inhibiting IC2's anti-tumor effects evaluated MTT assays apoptosis assays, which subsequently validated in vivo xenografted tumor model.Results exerted effects, resulting various cells. stimulated independent extracellular sources did not result increased de novo fatty acid (FA) synthesis within Transcriptional analysis indicated that disturbed mitochondrial functions, confirmed impaired membrane (MMP) reduced capacity Moreover, treatment led a greater accumulation lipids outside mitochondria compared control group. inhibited proliferation PC3 promoted These further enhanced after diacylglycerol acyltransferase (DGAT1), key enzyme involved formation. In PC3-xenografted mice, DGAT1 augmented reduction growth modulating formation.Conclusion feedback response compromises actions. IC2’s efficacy be combining it This strategy may extended other agents regulate metabolism.

Language: Английский

Traditional Chinese medicine for the treatment of cancers of hepatobiliary system: from clinical evidence to drug discovery DOI Creative Commons
Junyu Wu, Guping Tang, Chien‐shan Cheng

et al.

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Oct. 1, 2024

Language: Английский

Citations

13
Transplant oncology and anti-cancer immunosuppressants DOI Creative Commons
Dejun Kong,

Jinliang Duan,

Shiyi Chen

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

Organ transplantation is a life-saving intervention that enhances the quality of life for patients with end-stage organ failure. However, long-term immunosuppressive therapy required to prevent allogeneic graft rejection, which inadvertently elevates risk post-transplant malignancies, especially liver transplant recipients prior history cancer. In response, emerging field oncology integrates principles from and immunology improve outcomes at high tumor occurrence or recurrence following transplantation. Therefore, it substantial clinical significance develop immunosuppressants possess both anti-tumor properties. For instance, mTOR inhibitors demonstrate effects among antimetabolite drugs, recent studies indicate capecitabine, an chemotherapeutic, may also exhibit activity in clinic transplants suffering hepatocellular carcinoma. This review systematically explores potential dual support management elevated recurrence.

Language: Английский

Citations

1
Recent advances in regulating the cell cycle through inhibiting CDKs for cancer treatment DOI

Weijiao Chen,

Xujie Zhuang, Yuanyuan Chen

et al.

Chinese Journal of Natural Medicines, Journal Year: 2025, Volume and Issue: 23(3), P. 286 - 298

Published: March 1, 2025

Language: Английский

Citations

1
Icaritin Represses Autophagy to Promote Colorectal Cancer Cell Apoptosis and Sensitized Low‐Temperature Photothermal Therapy via Targeting HSP90‐TXNDC9 Interactions DOI Creative Commons
Dan He, Siliang Chen, Xiaoyun Wang

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Abstract Colorectal cancer (CRC) ranks among the leading causes of cancer‐related dea ths worldwide, and rising incidence mortality CRC underscores urgent need for better understanding management strategies. Icaritin (ICA) is metabolites icariin, a natural flavonoid glycoside compound derived from stems leaves Epimedium . It has broad spectrum antitumor activity inhibits proliferation, migration, invasion cells, S phase cell cycle arrest. exerts its effects against through repressing autophagy to promote apoptosis via interfering HSP90‐TXNDC9 interactions. The safety efficacy ICA are also affirmed in mouse xenograft model. Additionally, test whether synergistic with low‐temperature photothermal therapy (LTPTT), novel nanodrug delivery system, employing SiO 2 nanocarriers, designed aiming load materials polydopamine (PDA), folic acid (FA). This /Ica‐PDA‐FA multifunctional nanocomposite actively targets tumor tissues high affinity FA cells. Once internalized, acidic intracellular environment triggers controlled release ICA, inhibiting By LTPTT drug under near‐infrared illumination, dual effect achieved, holding promise enhancing therapeutic outcomes treatment.

Language: Английский

Citations

1
Decoding mitochondria's role in immunity and cancer therapy DOI Creative Commons
Yu Shrike Zhang, Hong Yan, Yuquan Wei

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2024, Volume and Issue: 1879(4), P. 189107 - 189107

Published: May 9, 2024

The functions of mitochondria, including energy production and biomolecule synthesis, have been known for a long time. Given the rising incidence cancer, role mitochondria in cancer has become increasingly popular. Activated by components released various pathways interact with each other to induce immune responses protect organisms from attack. However, play dual roles progression cancer. Abnormalities proteins, which are elementary structures closely linked oncogenesis. Both aberrant accumulation intermediates mutations enzymes result generation Therefore, targeting treat may be new strategy. Several drugs aimed at inhibiting mutated accumulated tested clinically. Here, we discuss current understanding interactions between mitochondrial functions, responses, Furthermore, as hopeful targets therapy, providing insights into future therapeutic strategies.

Language: Английский

Citations

6
Targeting cell death mechanisms: the potential of autophagy and ferroptosis in hepatocellular carcinoma therapy DOI Creative Commons
Beibei Liu,

Ling Liu,

Yang Liu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 9, 2024

Ferroptosis is a type of cell death that plays remarkable role in the growth and advancement malignancies including hepatocellular carcinoma (HCC). Non-coding RNAs (ncRNAs) have considerable impact on HCC by functioning as either oncogenes or suppressors. Recent research has demonstrated non-coding ability to control ferroptosis cells, hence impacting tumors resistance these cells drugs. Autophagy mechanism conserved throughout evolution maintaining balance body under normal settings. Nevertheless, occurrence dysregulation autophagy evident progression various human disorders, specifically cancer. dual roles cancer, potentially influencing both survival death. prevalent kind liver genetic mutations changes molecular pathways might worsen its advancement. The subject debate, it capacity repress promote tumor growth. activation can apoptosis, proliferation glucose metabolism, facilitate spread through EMT. Inhibiting hinder enhance respond treatment. regulated several signaling pathways, such STAT3, Wnt, miRNAs, lncRNAs, circRNAs. Utilizing anticancer drugs target may advantageous implications for efficacy cancer

Language: Английский

Citations

6
Mitochondria-Targeted Icaritin Nanoparticles Induce Immunogenic Cell Death in Hepatocellular Carcinoma DOI
Siyu Chen,

Yiyang Sun,

Yangla Xie

et al.

ACS Applied Materials & Interfaces, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 25, 2024

Hepatocellular carcinoma (HCC) is a highly malignant tumor that resistant to chemotherapy and immunotherapy. Icaritin (ICT), traditional Chinese medicine, has been reported as an immunoregulatory agent for treating advanced unresectable HCC. ICT induces mitophagy cause immunogenic cell death (ICD); however, the poor bioavailability of limits its therapeutic efficacy clinical use. Therefore, this study aimed assess effect using poly(2-(

Language: Английский

Citations

4
Single-cell mitophagy patterns within the tumor microenvironment modulate intercellular communication, impacting the progression and prognosis of hepatocellular carcinoma DOI Creative Commons

Zhengyan Li,

Wei Chen, Yao Shu

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 6, 2025

Hepatocellular carcinoma (HCC) is a common malignant tumor of the digestive system with high incidence that seriously threatens patients' lives and health. However, rise application new treatments, such as immunotherapy, there are still some restrictions in treatment diagnosis HCC, therapeutic effects on patients not ideal. Two single-cell RNA sequencing (scRNA-seq) datasets from HCC patients, encompassing 25,189 cells, were analyzed study. We utilized non-negative matrix factorization (NMF) clustering to identify mitophagy patterns TME including cancer-associated fibroblasts (CAFs), T B tumor-associated macrophages (TAMs). Cell-to-cell communication was using CellChat package, pseudotime trajectory analysis performed Monocle package. Gene regulatory networks investigated SCENIC survival analyses conducted mitophagy-related signatures. samples identified 22 clusters, 7 principal cell types. Complex communications observed among these Mitophagy-related CAFs, TAMs, CD8+ cells identified. These subtypes had different biological states, cell-cell communications, metabolic pathways. Mitophagy levels elevated samples. Changes genes within specific associated overall rates. did seem affect effectiveness immunotherapy. This study provides evidence modulates intercellular communication, influencing progression patient prognosis. Targeting may offer promising approach improve long-term prognosis patients.

Language: Английский

Citations

0
Advances in Pharmacological Research on Icaritin: A Comprehensive Review DOI
Ran Guo, Zhiping Yan,

Rui Wang

et al.

The American Journal of Chinese Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 25

Published: Jan. 29, 2025

Epimedium has been widely used in traditional Chinese medicine for several thousands of years. This plant is known tonifying kidney Yang, strengthening muscles and bones, dispelling wind dampness. It worth noting that icaritin, a prenylated flavonoid isolated from Epimedium, received increasing attention recent years due to its wide range pharmacological activities. Icaritin exhibits significant therapeutic potential against various diseases, such as osteoporosis, tumors (hepatocellular carcinoma, stomach cancer, breast glioblastoma), cerebral ischemia skin injury, thrombocytopenia, systemic lupus erythematosus. We review the activities icaritin molecular mechanisms treatment related diseases. The data suggest can have effects mediating Wnt/[Formula: see text]-catenin, IL-6/JAK2/STAT3, AMPK/mTOR, PTEN/AKT, MAPK, NF-[Formula: text]B, other signaling pathways. paper also discusses progress clinical trials icaritin. was approved by State Food Drug Administration January 2022 advanced HCC, drug prospects. Although it some disadvantages, including poor solubility, low bioavailability, still prospective candidate development naturally derived drugs, especially inflammatory aims update deepen understanding provide theoretical basis further study.

Language: Английский

Citations

0
Antineoplastic effects of icaritin: molecular mechanisms and applications DOI Creative Commons
Piao Luo, Liyang Zhang,

Guangqing Cheng

et al.

Acta Materia Medica, Journal Year: 2025, Volume and Issue: 4(2)

Published: Jan. 1, 2025

Icaritin (ICA) is a prenylflavonoid natural product extracted from plants of the Epimedium genus. The approval ICA softgel capsules as class 1.2 traditional Chinese medicine (TCM) innovative drug represents major advancement offering novel therapeutic approach for patients with advanced hepatocellular carcinoma (HCC). Class TCM drugs generally denote extracts and formulations derived single plants, animals, minerals, or other substances. exhibits diverse pharmacological effects, encompassing anti-inflammatory, immune-regulatory, anti-oxidation, anti-osteoporosis, anti-depression, notably anti-cancer properties. This review presents comprehensive overview molecular mechanisms underlying properties ICA, further highlights recent progress in use cancer research, discusses present challenges, examines potential opportunities application development.

Language: Английский

Citations

0