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. 2025 Dec 31;28(4):290–300. doi: 10.3831/KPI.2025.28.4.290

Inhibition of Adrenergic Agonist–Induced Metastatic Potential in Cancer Cells by an Ethanolic Extract of Lindera aggregata Root Tuber

Jae-Hoon Jeong 1,†, Shin-Hyung Park 1,†,*
PMCID: PMC12745366  PMID: 41477278

Abstract

Objectives

The root tuber of Lindera aggregata (LA) has been traditionally used in Korean medicine to promote qi circulation and alleviate pain. This study investigated the anti-metastatic effects of an ethanolic extract of LA (ELA) and explored its underlying molecular mechanisms.

Methods

The effect of ELA on adrenergic agonist–induced cancer cell migration and invasion was evaluated using transwell assays. The influence of ELA on Src phosphorylation induced by adrenergic agonists was assessed via Western blot analysis. Network pharmacology analysis was conducted based on the known and predicted targets of ELA, including KEGG pathway enrichment, Gene Ontology (GO) enrichment, protein–protein interaction (PPI) network construction, and disease association analysis.

Results

Migration of MDA-MB-231 breast cancer cells and Hep3B hepatocellular carcinoma cells was promoted by adrenergic agonists, including epinephrine (E), norepinephrine (NE), and isoprenaline (ISO). This effect was significantly reversed by ELA in a concentration-dependent manner. Similarly, E- and NE-induced cancer cell invasion was suppressed by ELA in a dose-dependent manner. ELA also inhibited E- and NE-stimulated Src phosphorylation, suggesting that the anti-metastatic effects of ELA are mediated through Src inactivation. Network pharmacology analysis identified Src as a central hub protein potentially mediating the effects of LA. In addition, enrichment analysis revealed significant involvement of LA targets in cancer-related pathways and cell motility processes, further supporting the experimental findings.

Conclusion

These findings suggest that ELA inhibits adrenergic agonist–induced metastatic activity in cancer cells by deactivating Src, highlighting its potential as a novel anti-metastatic therapeutic agent.

Keywords: Lindera aggregata root tuber, cancer, migration, invasion, Src

INTRODUCTION

Chronic stress has been reported as a significant factor contributing to cancer progression and therapeutic resistance [1, 2]. Clinical evidence indicates that prolonged stress in cancer patients is associated with higher recurrence rates and poorer overall survival compared with patients not experiencing stress [3, 4]. Notably, psychological interventions—including stress management, counseling, and cognitive-behavioral therapy—have been associated with improved clinical outcomes [4-6]. At the physiological level, chronic stress induces sustained activation of the hypothalamic–pituitary–adrenal (HPA) axis and the sympathetic nervous system (SNS), resulting in elevated levels of glucocorticoids and catecholamines [7, 8]. These stress hormones promote cancer progression by inducing angiogenesis and metastasis while suppressing antitumor immunity [7, 8].

Catecholamines, including epinephrine (E) and norepinephrine (NE), promote cancer metastasis by activating the adrenergic signaling pathway, primarily via β-adrenergic receptors (β-ARs) expressed on both cancer cells and stromal components of the tumor microenvironment (TME) [9, 10]. Upon activation, β-ARs trigger several downstream signaling cascades—including the cyclic AMP (cAMP)/protein kinase A (PKA)/cAMP response element-binding protein (CREB) pathway, the exchange protein directly activated by cAMP (EPAC) pathway, and the Src kinase pathway—all of which contribute to the regulation of genes involved in cancer cell migration and invasion [9, 10]. Additionally, adrenergic signaling upregulates vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs), promoting metastasis through enhanced angiogenesis and extracellular matrix (ECM) remodeling [9, 10]. These mechanistic insights have generated interest in β-blockers as potential adjuvant agents to attenuate stress-mediated cancer progression and improve clinical outcomes [11]. Among them, propranolol, a non-selective β-AR antagonist, has been reported to prolong relapse-free survival, suppress metastasis, and reduce cancer-related mortality across several cancer types [11-13].

The root tuber of Lindera aggregata (LA) has been traditionally used in Korean medicine to promote qi circulation and alleviate pain [14]. It is commonly prescribed for conditions such as chest fullness, abdominal pain, and gynecological disorders [14]. Pharmacological studies have demonstrated that the LA root tuber exhibits a broad spectrum of biological activities, including anti-inflammatory, antioxidant, hepatoprotective, antibacterial, lipid-lowering, and anti-cancer effects [14-18]. Its anticancer properties are mediated through the modulation of various molecular targets, including p53, caspases, nuclear factor kappa B (NF-κB), and signal transducer and activator of transcription 3 (STAT3) signaling pathways [19-22]. However, its potential anti-metastatic effects remain unexplored. According to Korean medicine, psychological stress induces qi stagnation, which may contribute to cancer progression and metastasis. Thus, it can be hypothesized that stress-induced cancer metastasis may be alleviated by herbal medicines that promote qi circulation. In the present study, we examined the effects of LA root tuber—a representative qi-regulating herb—on the metastatic capacity of cancer cells stimulated by adrenergic agonists, and investigated the underlying molecular mechanisms.

MATERIALS AND METHODS

1. Preparation of ELA

A total of 20 g of dried root tuber of LA, sourced from Bonchomaru (Seoul, Korea), was subjected to a two-step extraction using 80% ethanol. The first extraction was performed with 200 mL of 80% ethanol at 40℃ under continuous agitation at 150 rpm for 48 h. A second extraction was then conducted with 100 mL of 80% ethanol under identical conditions for an additional 24 h. After centrifugation and filtration to remove insoluble residues, the extract was evaporated under reduced pressure and lyophilized, yielding 1.65 g of dry powder (yield: 8.3%). The powder was dissolved in dimethyl sulfoxide (DMSO; Amresco, Solon, OH, USA) at a concentration of 100 mg/mL to prepare a stock solution, which was designated as ELA.

2. Cell culture

The MDA-MB-231 human breast cancer cell line and the Hep3B human hepatocellular carcinoma (HCC) cell line were obtained from the American Type Culture Collection (ATCC; Rockville, MD, USA). Cell culture was conducted using RPMI-1640 medium (WelGENE, Daegu, Korea) supplemented with 10% FBS, 100,000 U/L penicillin, and 100 mg/L streptomycin (WelGENE) for MDA-MB-231 cells, and DMEM (WelGENE) containing the same concentrations of FBS, penicillin, and streptomycin for Hep3B cells. All cells were incubated at 37℃ in a humidified atmosphere with 5% CO₂.

3. MTT assay

Cells (3 × 10³ per well) were seeded into 96-well plates, allowed to stabilize overnight, and treated with ELA (0.1-100 μg/mL) in 100 μL of culture medium. Following a 24 h exposure to ELA, 10 μL of 4 mg/mL MTT solution (Duchefa, Haarlem, The Netherlands) was added to each well, and the cells were incubated at 37℃ for an additional 2 h. The medium was then discarded, and 100 μL of DMSO was added to each well to dissolve the formed formazan crystals. Absorbance at 540 nm was measured using a microplate reader (Molecular Devices, San Jose, CA, USA) to assess cell viability.

4. Transwell assay

For transwell migration assays, 2 × 10⁴ Hep3B cells or 3 × 10⁴ MDA-MB-231 cells were suspended in 200 μL of serum-free medium containing adrenergic agonists and ELA (25-100 μg/mL), and seeded into the inserts of 24-well Transwell plates (Corning, NY, USA). A 0.1% gelatin solution (Sciencell, Carlsbad, CA, USA) was used to coat the outer membrane of the inserts. The lower chambers contained 600 μL of medium supplemented with 10% FBS as a chemoattractant. After 24 h, the medium in the inserts was aspirated, and the membranes were fixed with methanol for 5 min and stained with hematoxylin (Sigma-Aldrich) for 30 min. The inner side of each insert was gently cleaned using a cotton swab and rinsed with DW. Membranes were excised and examined under a microscope (Carl Zeiss, Oberkochen, Germany) at ×100 magnification. Cell migration was quantified by counting stained cells per field. Transwell invasion assays were conducted similarly, except that the inner surfaces of the inserts were coated with 300 μg/mL Matrigel (BD Biosciences, San Jose, CA, USA) before cell seeding.

5. Western blot analysis

Cells (2 × 106) were plated in 60 mm culture dishes and allowed to stabilize overnight, then exposed to varying concentrations of ELA (25-100 μg/mL). At 22 h post-treatment, cells were challenged with E (10 μM) or NE (1 μM) for an additional 2 h. Cells were lysed using RIPA buffer (Thermo Fisher Scientific, San Jose, CA, USA) to isolate total protein, which was quantified using a bicinchoninic acid protein assay kit (Pierce Biotechnology, Rockford, IL, USA). Proteins (20 μg) were resolved by SDS-PAGE and transferred to PVDF membranes (Millipore Corporation, Bedford, MA, USA). Membranes were blocked with 3% BSA (GenDEPOT, TX, USA) for 30 min and incubated overnight at 4℃ with primary antibodies (1:1,000 dilution in 3% BSA). The next day, membranes were rinsed several times with TBST and incubated with HRP-conjugated secondary antibodies (1:5,000 dilution) for 50 min at room temperature. Chemiluminescence was detected using the D-Plus ECL Femto System (Donginbio, Seoul, Korea). Phospho-Src (Y416) antibody was purchased from Cell Signaling Technology (Beverly, MA, USA), while total Src and actin antibodies were purchased from Santa Cruz Biotechnology (Santa Cruz, CA, USA). HRP-conjugated anti-mouse and anti-rabbit secondary antibodies were obtained from Enzo Life Sciences (Farmingdale, NY, USA).

6. Network pharmacology analysis

Known and predicted target proteins of LA, along with the corresponding gene ontology (GO) enrichment analysis results, were retrieved from BATMAN-TCM (https://bionet.ncpsb.org/batman-tcm/). Functional significance of LA targets was further investigated using Enrichr (https://maayanlab.cloud/Enrichr/). KEGG 2021 Human pathway enrichment and PPI Hub Protein analyses were performed using Enrichr to identify associated signaling pathways and central hub proteins within protein–protein interaction networks. Disease associations were also examined using the DisGeNET module in Enrichr to identify diseases potentially linked to LA target genes. For all analyses, p-value-based rankings were used to select the top 10 or 20 entries, and graphical visualization was performed using Microsoft Excel based on -log10(p-value).

7. Statistical analysis

Results are expressed as the mean ± SD from triplicate experiments. Statistical analyses were conducted using one-way ANOVA with Tukey’s post hoc test for group comparisons. A p-value < 0.05 was considered statistically significant.

RESULTS

1. Determination of non-cytotoxic concentrations of ELA

We first determined the non-cytotoxic concentrations of ELA in MDA-MB-231 human breast cancer cells and Hep3B human HCC cells to exclude the possibility that its growth-inhibitory effects might influence cancer cell migration or invasion. Cell viability was evaluated by MTT assay following a 24 h treatment with varying concentrations of ELA (0.1-100 μg/mL). As shown in Fig. 1A and B, ELA exhibited minimal cytotoxicity at concentrations up to 100 μg/mL, with cell viability remaining above 90% in both cell lines. Therefore, 100 μg/mL was selected as the maximum concentration.

Figure 1.

Figure 1

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Effects of ELA on cancer cell viability. MDA-MB-231 human breast cancer cells (A) and Hep3B human hepatocarcinoma cells (B) were treated with ELA (0.1-100 μg/mL) for 24 h. Cell viability was assessed using the MTT assay. The dotted line represents 90% cell viability. Data are expressed as the mean ± SD from three independent experiments. ELA, ethanolic extract of Lindera aggregata root tuber.

2. Effects of ELA on adrenergic agonist-induced migration of breast cancer cells

Catecholamines released under psychological stress are widely known to promote cancer cell migration and invasion, both of which are pivotal to metastasis [9, 10]. Consistently, we found that treatment with non-selective adrenergic agonists, such as E and NE, and the β-AR–selective agonist ISO, markedly enhanced the migratory ability of MDA-MB-231 breast cancer cells (Fig. 2A, B). These results align with earlier studies showing that adrenergic stimulation increases the migratory capacity of breast cancer cells—an effect fully abrogated by β-AR blockers [23, 24]. Notably, ELA treatment dose-dependently inhibited migration triggered by adrenergic agonists in MDA-MB-231 cells, suggesting that ELA may counteract stress-mediated migration in breast cancer (Fig. 2A, B).

Figure 2.

Figure 2

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Effects of ELA on breast cancer cell migration. The migratory ability of MDA-MB-231 human breast cancer cells treated with epinephrine (E; 1 μM, upper), norepinephrine (NE; 1 μM, middle), or isoprenaline (ISO; 10 μM, lower) in the presence or absence of ELA (25-100 μg/mL). Migration was assessed using a transwell migration assay. Migrated cells were stained and imaged at ×100 magnification (scale bar = 100 μm). Representative images from three independent experiments are shown (A). Relative migration was quantified by counting stained cells (B). Data are presented as the mean ± SD of three independent experiments. Statistical significance was evaluated using one-way ANOVA followed by Tukey’s post hoc test (###p < 0.001 versus untreated control; ***p < 0.001 versus adrenergic agonists-treated cells). ELA, ethanolic extract of Lindera aggregata root tuber.

3. Influence of ELA on adrenergic agonist-stimulated migration of HCC cells

To further verify the anti-migratory effects of ELA in another cancer type, Hep3B human HCC cells were employed. Like MDA-MB-231 cells, both E and ISO markedly increased Hep3B cell migration (Fig. 3A, B), consistent with our previous findings [23]. ELA treatment suppressed adrenergic agonist-induced migration in a concentration-dependent manner (Fig. 3A, B). Combined with the data presented in Fig. 2, these findings suggest that ELA may broadly inhibit stress-induced cancer cell migration across multiple cancer types.

Figure 3.

Figure 3

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Effects of ELA on HCC cell migration. The migratory ability of Hep3B human hepatocellular carcinoma (HCC) cells treated with epinephrine (E; 10 μM, upper) or isoprenaline (ISO; 10 μM, lower) in the presence or absence of ELA (25-100 μg/mL). Migration was assessed using a transwell migration assay. Migrated cells were stained and imaged at ×100 magnification (scale bar = 100 μm). Representative images from three independent experiments are shown (A). Relative migration was quantified by counting stained cells (B). Data are presented as the mean ± SD of three independent experiments. Statistical significance was evaluated using one-way ANOVA followed by Tukey’s post hoc test (###p < 0.001 versus untreated control; ns, not significant, **p < 0.01, ***p < 0.001 versus adrenergic agonists-treated cells). ELA, ethanolic extract of Lindera aggregata root tuber.

4. Effects of ELA on adrenergic agonist-induced cancer cell invasion

We next examined the influence of ELA on invasion induced by adrenergic agonists in MDA-MB-231 and Hep3B cells. Consistent with previous studies showing that adrenergic agonists promote invasion in breast and HCC cells [23, 24], treatment with E or NE significantly enhanced the invasive capacity of both cell lines (Fig. 4A, B). Notably, the invasion-promoting effects of E and NE were completely abolished by ELA (Fig. 4A, B), indicating that ELA can inhibit stress-driven invasive behavior in diverse cancer cell types. Together with the results in Fig. 2 and Fig. 3, these findings suggest that ELA exerts anti-metastatic effects in stress-related catecholamine signaling.

Figure 4.

Figure 4

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Effects of ELA on cancer cell invasion. The invasive capacity of MDA-MB-231 human breast cancer cells (upper) and Hep3B human hepatocellular carcinoma (HCC) cells (lower) treated with norepinephrine (NE; 1 μM, for MDA-MB-231 cells) or epinephrine (E; 10 μM, for Hep3B cells) in the presence or absence of ELA (25-100 μg/mL). Migration was assessed using a transwell invasion assay. Invaded cells were stained and imaged at ×100 magnification (scale bar = 100 μm). Representative images from three independent experiments are shown (A). Relative invasion was quantified by counting stained cells (B). Data are presented as the mean ± SD of three independent experiments. Statistical significance was evaluated using one-way ANOVA followed by Tukey’s post hoc test (###p < 0.001 versus untreated control; **p < 0.01, ***p < 0.001 versus adrenergic agonist-treated cells). ELA, ethanolic extract of Lindera aggregata root tuber.

5. Effects of ELA on Src phosphorylation induced by adrenergic agonists in cancer cells

We next investigated the molecular mechanisms underlying the anti-metastatic effects of ELA. Our previous findings demonstrated that Src plays a central role in migration and invasion triggered by adrenergic agonists [23]. Accordingly, we examined whether ELA affects Src activity. Treatment with E or NE markedly increased the phosphorylation levels of Src kinase, which were substantially reversed by ELA in both cell lines (Fig. 5). As Src activation is dependent on phosphorylation, these findings suggest that inhibition of adrenergic agonist-induced Src activation contributes to the anti-metastatic effects of ELA.

Figure 5.

Figure 5

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Effects of ELA on Src phosphorylation in cancer cells. MDA-MB-231 human breast cancer cells (A, C) and Hep3B human hepatocellular carcinoma (HCC) cells (B, D) were treated with ELA (25-100 μg/mL) for 22 h, followed by stimulation with norepinephrine (NE; 1 μM, for MDA-MB-231 cells) or epinephrine (E; 10 μM, for Hep3B cells) for an additional 2 h. Phosphorylated and total Src levels were analyzed by Western blotting; actin served as a loading control. Representative blots from three independent experiments are shown (A, B). The ratio of phosphorylated to total Src was quantified by measuring band intensities (C, D). Data are presented as the mean ± SD of three independent experiments. Statistical significance was evaluated using one-way ANOVA followed by Tukey’s post hoc test (##p < 0.01 versus untreated control; **p < 0.01, ***p < 0.001 versus adrenergic agonist-treated cells). ELA, ethanolic extract of Lindera aggregata root tuber.

6. Network pharmacological profiling of LA targets implicated in cancer metastasis

Using the BATMAN-TCM database, a total of 301 known and predicted target genes of the LA root tuber were identified. To gain systems-level insight into the anti-metastatic actions of ELA, these targets were subjected to functional enrichment and network-based analyses. KEGG 2021 Human pathway enrichment revealed that the top enriched pathway was pathways in cancer, suggesting that LA may affect tumor growth and metastasis through modulation of oncogenic signaling pathways (Fig. 6A). GO biological process analysis showed enrichment of metastasis-related categories, including locomotion, cell motility, signal transduction, and cell–cell signaling, indicating that LA targets may affect cellular behaviors critical for metastasis, such as migration, invasion, and intracellular communication within the TME (Fig. 6B). PPI hub protein analysis identified Src as one of the top 10 hub proteins potentially mediating LA effects (Fig. 6C, D), supporting our experimental results showing reduced Src phosphorylation after ELA treatment (Fig. 5). In addition, DisGeNET-based disease enrichment analysis showed that liver neoplasms and liver carcinoma were among the top 10 diseases associated with LA targets (Fig. 6E). Among the top 30 enriched disease terms, various cancer types were represented, including neuroblastoma, ovarian carcinoma, lung carcinoma, colon carcinoma, and prostate carcinoma, suggesting that LA targets may be broadly implicated in cancer progression (data not shown).

Figure 6.

Figure 6

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Network pharmacological analysis of LA targets. Predicted targets of LA root tuber were identified using the BATMAN-TCM database and analyzed for functional enrichment and network interactions. (A) Top 10 enriched pathways based on the KEGG 2021 Human dataset. (B) Top 20 enriched biological processes identified by Gene Ontology (GO) analysis. (C) Top 10 hub proteins regulating the target gene set. (D) Protein-protein interaction (PPI) network visualization of the top 10 hub proteins. (E) Top 10 enriched diseases based on DisGeNET. All results were ranked by –log10(p-value). Arrows indicate categories associated with cancer metastasis. LA, Lindera aggregata root tuber.

DISCUSSION

In this study, we investigated the anticancer effects of ELA, with particular emphasis on its inhibitory activity against the metastatic behavior of cancer cells. The novelty of our study lies in the following aspects. First, we demonstrated for the first time that the total extract of LA root tuber exhibits anti-metastatic effects. Although isolinderalactone, a well-characterized constituent of LA, has been reported to inhibit the migration and invasion of lung cancer cells [19], prior studies on the anticancer effects of LA have largely focused on individual compounds rather than the whole extract [19-22]. In contrast, our study employed the total extract, which more accurately reflects the traditional clinical use of LA root tuber and allows evaluation of potential synergistic or antagonistic interactions among its multiple components. Second, our study modeled chronic stress-induced catecholamine release to stimulate cancer metastasis. According to traditional Korean medicine, psychological stress is linked to qi stagnation, and LA root tuber is commonly used to promote qi circulation. Therefore, we hypothesized that LA may counteract stress-mediated cancer metastasis. By demonstrating that ELA inhibits adrenergic agonist–induced cancer cell migration and invasion, our findings provide scientific evidence supporting the potential application of traditional herbal medicines that promote qi circulation under conditions of psychological stress–related qi stagnation. This represents the overarching significance of the current study.

We chose to focus on breast cancer and HCC cells to investigate the anti-metastatic effects of ELA under stress-related conditions for the following reasons. First, chronic stress-induced adrenergic activation has been implicated in tumor progression in both cancer types. In breast cancer, chronic stress has been linked to increased tumor growth, metastasis, and chemoresistance, partly through the β-AR signaling pathway [25-27]. Similarly, in HCC, stress-induced adrenergic activation has been reported to accelerate tumor progression by activating hepatic stellate cells and inducing fibrotic remodeling, ultimately contributing to the establishment of a pro-metastatic niche [27-30]. Second, previous studies have primarily focused on the use of qi-circulating herbal medicines for the treatment of breast and liver cancers in cancer therapy [31, 32]. In traditional Korean medicine, qi stagnation is primarily associated with the liver. A search for studies combining “liver-soothing” and “cancer” on CNKI (www.cnki.net) yielded 253 preclinical and clinical research articles published between 2000 and 2020, of which 118 focused on liver cancer and 64 on breast cancer, highlighting the predominant application of liver-soothing and qi-regulating strategies to these cancer types. In this study, we specifically selected MDA-MB-231 breast cancer cells and Hep3B HCC cells among various breast and HCC cancer cell lines. This selection was based on our previous findings showing that these two cell lines exhibited the highest expression of the ADRB2 gene, which encodes β2-AR, within their respective cancer types [23]. Among the different AR subtypes, β2-AR is known to play the most critical role in promoting cancer progression [9].

We investigated Src kinase as a potential molecular mechanism underlying the anti-metastatic effects of ELA. Src is a non-receptor tyrosine kinase involved in key cellular processes, including proliferation, survival, and motility [33]. Src is highly activated in various cancer types and plays a critical role in metastasis by promoting cell migration and invasion [34]. It exerts these effects through downstream targets that regulate cytoskeletal remodeling and focal adhesion turnover, as well as through the upregulation of MMPs that facilitate ECM degradation. Thus, aberrant Src activation is closely related to increased metastasis and poor prognosis [34-36]. Notably, our previous study demonstrated that adrenergic agonists stimulate cancer cell migration and invasion via activation of the β2-AR/Src axis, highlighting the importance of Src regulation in the context of cancer metastasis under chronic psychological stress [23]. In the present study, we found that E- or NE-induced Src phosphorylation was markedly suppressed by ELA treatment. Furthermore, network pharmacological analysis identified Src as a critical hub protein of LA, corroborating experimental findings. These results suggest that inhibition of Src activity may mediate the anti-metastatic effects of ELA and highlight its potential as a therapeutic option for preventing stress-related cancer metastasis.

Despite the novelty and academic significance of this study, several limitations warrant consideration. First, the specific components responsible for the anti-metastatic effects of ELA were not identified. Second, this study was limited to in vitro experiments, and further in vivo and clinical validation is needed. Third, additional mechanisms beyond Src inhibition may contribute to the anti-metastatic effects of ELA. For example, “Fluid shear stress and atherosclerosis” and “Lipid and atherosclerosis” were among the top pathways identified in the KEGG pathway enrichment analysis. Given that fluid shear stress regulates mechanotransduction and metastatic dissemination, ELA may modulate mechanosensitive signaling pathways beyond Src activation [37]. Furthermore, it may influence lipid metabolism, attenuate inflammatory responses, and stabilize the endothelial barrier, thereby inhibiting cancer cell intravasation [38, 39]. Therefore, further studies are warranted to elucidate the multifaceted anti-metastatic mechanisms of ELA across multiple biological processes.

CONCLUSION

In this study, we demonstrated that ELA inhibits adrenergic agonist–inducedmetastatic activity and Src phosphorylation in cancer cells. Network pharmacological analysis revealed that LA targets are enriched in cancer- and metastasis-related pathways, with Src identified as a key hub protein. Although the specific bioactive components remain unidentified and in vivo validation is needed, our findings suggest that ELA may serve as a potential therapeutic option to prevent stress-related cancer metastasis. Moreover, our results indicate that qi-circulating strategies could provide an effective approach for managing cancer progression in patients experiencing chronic psychological stress.

Footnotes

DATA AVAILABILITY

The data that support the findings of this study are available from the corresponding author upon reasonable request.

AUTHORS’ CONTRIBUTIONS

Conceptualization: Shin-Hyung Park; Methodology: Shin-Hyung Park; Validation: Jae-Hoon Jeong; Formal analysis: Jae-Hoon Jeong and Shin-Hyung Park; Investigation: Jae-Hoon Jeong and Shin-Hyung Park; Project administration: Shin-Hyung Park; Visualization: Jae-Hoon Jeong and Shin-Hyung Park; Supervision: Shin-Hyung Park; Writing – Original draft: Shin-Hyung Park; Writing – Review & Editing: Jae-Hoon Jeong and Shin-Hyung Park.

CONFLICTS OF INTEREST

The authors declare that they have no conflicts of interest.

FUNDING

This work was supported by Dong-Eui University Foundation Grant (2024) and Dong-Eui University Foundation Grant (202500620001).

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