Biological Activity

Bioactivity / Mechanism

Dihydrotanshinone I inhibits HuR–RNA complex formation in biochemical assays, with a reported Ki of 3.74 ± 1.63 nM. Kinetic experiments indicate that it mainly prevents association rather than displacing preformed complexes. HuD–RNA binding was also affected in the comparator panel, so these results do not establish exclusive HuR selectivity. [1]

Cellular effects on HuR binding depend on the transcript. In HeLa cells, DHTS reduced binding of 79 of 2306 HuR-associated mRNAs but enriched binding of 558; selected changes were validated by RT-qPCR. These findings limit interpretation of DHTS as a uniform suppressor of all HuR–RNA interactions. [2]

Literature-reported observations and conditions; not Adooq-tested protocols or general treatment recommendations.

Cellular Effect

Cell Line	Activity	Value	Description	Reference
AGS	IC50	> 50 μM	Viability of human AGS cells under normoxic conditions after 24 hrs by MTT assay	[PMID: 17583950]
AGS	IC50	2.05 μM	Inhibition of HIF1 activation in human AGS cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay	[PMID: 17583950]
AGS	IC50	47.7 μM	Viability of human AGS cells under hypoxic conditions after 24 hrs by MTT assay	[PMID: 17583950]
Hep 3B2	IC50	> 50 μM	Viability of human Hep3B cells under normoxic conditions after 24 hrs by MTT assay	[PMID: 17583950]
Hep 3B2	IC50	> 50 μM	Viability of human Hep3B cells under hypoxic conditions after 24 hrs by MTT assay	[PMID: 17583950]
Hep 3B2	IC50	2.29 μM	Inhibition of HIF1 activation in human Hep3B cells assessed as inhibition of hypoxia-induced luciferase expression after 16 hrs by reporter assay	[PMID: 17583950]
Hep 3B2	EC50	5.5 μM	Cytotoxicity against human Hep3B cells deficient in p53 gene by MTT assay	[PMID: 20455578]
HepG2	EC50	2.5 μM	Cytotoxicity against human HepG2 cells expressing wild type p53 gene by MTT assay	[PMID: 20455578]
HepG2	EC50	4.7 μM	Cytotoxicity against doxorubicin resistant human HepG2 cells expressing wild type p53 gene by MTT assay	[PMID: 20455578]
MCF7	IC50	3.73 μM	Cytotoxicity against human MCF7 cells assessed as decrease in cell viability after 72 hrs by OZBlue assay	[PMID: 29313684]
MDA-MB-231	IC50	8.99 μM	Cytotoxicity against human MDA-MB-231 cells assessed as decrease in cell viability after 72 hrs by OZBlue assay	[PMID: 29313684]
PANC-1	IC50	2.91 μM	Cytotoxicity against human PANC1 cells assessed as decrease in cell viability after 72 hrs by OZBlue assay	[PMID: 29313684]
PLC-PRF-5	EC50	> 10 μM	Cytotoxicity against human PLC/PRF/5 cells expressing mutant p53 gene (codon 249) by MTT assay	[PMID: 20455578]

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In Vitro Studies

In Caco-2 cells, pretreatment with 6 μM DHTS for 60 minutes reduced migration during subsequent 48-hour stimulation with 100 μM ATP compared with ATP alone. This scratch-assay result applies to ATP-stimulated migration and does not establish a stand-alone antiproliferative potency. [3]

HuR-RNA binding inhibition and specificity controls

Biochemical assay · Recombinant human HuR and TNF AU-rich-element RNA probe; comparator RNA-binding proteins [1]

DHTS inhibited formation of the HuR-RNA complex and mainly prevented association rather than disrupting the preformed complex. The reported fitted Ki is assay-specific. HuD-RNA binding was also affected, limiting claims of exclusive HuR selectivity.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Inhibition of HuR-TNF ARE RNA complex formation; Ki fitted using fixed RNA concentration 50 nM and Kd 2.5 nM	Ki 3.74 ± 1.63 nM	[1]
RNA-binding protein comparator panel	Qualitative binding response HuD affected; Lin28b, TTP and TDP-43 not substantially affected at tested concentrations	[1]

Literature-Reported Treatment Conditions

Treatment concentration: Assay-dependent titration; Figure 1A screening: 50 nM; Figure 2C comparator panel: 2.5 and 5 μM.
Exposure duration: Equilibrium assays and kinetic experiments; preformed-complex control used 30 min pre-incubation.
Method: AlphaScreen and RNA electrophoretic mobility shift assay (REMSA)
Vehicle: DMSO
Co-treatment: None
Reported limits: Exact equilibrium incubation duration and final DMSO percentage were not established from the selected main-text material; SI PDF acquired but not read.

Methods and source locations

Compound reported in the paper: Dihydrotanshinone I; Compound label in the paper: DHTS

Compound-level research evidence; tested material and model remain study-specific.

Results, first subsection; Figure 1B-G and Figure 2C; Methods, Compounds and primary antibodies, AlphaScreen and REMSA assays

Inhibition of HuR-TNF ARE RNA complex formation; Ki fitted using fixed RNA concentration 50 nM and Kd 2.5 nM: One-site competition fit; mean ± SD, n = 3 independent experiments per Figure 1 caption — Results, first subsection; Figure 1D annotation and caption; Methods, AlphaScreen and REMSA assays

RNA-binding protein comparator panel: REMSA at DHTS 2.5 and 5 μM, Figure 2C; representative binding patterns, n = 3 independent experiments per caption — Results, first subsection, final paragraph; Figure 2C image/caption

Transcript-dependent redistribution of HuR binding in HeLa cells

Cell-based study · Human HeLa cervical adenocarcinoma cells; endogenous HuR RNA immunoprecipitation and microarray [2]

DHTS did not uniformly remove transcripts from HuR. Among 2306 HuR-bound mRNAs, binding decreased for 79 and increased for 558. RT-qPCR validation included enriched, unchanged and depleted targets; total levels of the selected validation transcripts were generally unchanged.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Number of HuR-bound mRNAs with altered binding after DHTS treatment	Transcript counts 2306 bound mRNAs; 79 with reduced binding; 558 enriched	[2]

Literature-Reported Treatment Conditions

Treatment concentration: 1 μM (original GEO GSE94360 overall design)
Exposure duration: 3 hours (GSE94360 overall design)
Method: Cell exposure followed by endogenous HuR immunoprecipitation and RNA analysis
Vehicle: DMSO
Co-treatment: None
Reported limits: Microarray performed in duplicate and validation in triplicate; biological versus technical replicate identity is not specified in the figure caption.

Methods and source locations

Compound reported in the paper: Dihydrotanshinone I; Compound label in the paper: DHTS

Compound-level research evidence; tested material and model remain study-specific.

Results SEC3-6; Figure 4F-H; Methods SEC2-6 and SEC2-7; GEO GSE94360 overall design

Number of HuR-bound mRNAs with altered binding after DHTS treatment: RIP-chip, n = 2 microarray experiments; RT-qPCR validation n = 3 as captioned — Results SEC3-6, opening paragraph; Figure 4F-H caption; Methods SEC2-6

Attenuation of ATP-stimulated Caco-2 migration

Cell-based study · Human Caco-2 colorectal cancer cells; scratch wound healing assay [3]

DHTS pretreatment reduced ATP-stimulated migration relative to ATP alone. The figure includes vehicle control, ATP alone and separate ATP-plus-PPADS and ATP-plus-marimastat comparator groups. This supports a pharmacological association in this model; direct HuR target engagement was not measured by the scratch assay.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
ATP-stimulated rate of migration compared with ATP alone	Directional result and significance Reduced; p < 0.001 versus ATP-treated cells	[3]

Literature-Reported Treatment Conditions

Treatment concentration: DHTS 6 μM; ATP 100 μM
Exposure duration: DHTS pretreatment for 60 min before ATP stimulation for 48 hours
Method: Scratch wound healing assay; migration quantified using ImageJ
Vehicle: Vehicle control included; treatment vehicle identity not specified in the selected text.
Co-treatment: DHTS plus ATP; PPADS and marimastat were separate comparator treatments.
Reported limits: Mitomycin C pretreatment to suppress proliferation is described, but its dose is not specified in the selected Methods; no DHTS-alone arm is shown in Figure 8.

Methods and source locations

Compound reported in the paper: Dihydrotanshinone I; Compound label in the paper: DHTS

Compound-level research evidence; tested material and model remain study-specific.

Results Sec21; Figure 8 image and caption; Methods Sec3, Sec4, Sec10, Sec12

ATP-stimulated rate of migration compared with ATP alone: Scratch wound healing; mean ± SD, n = 3 as reported; ANOVA with Tukey-Kramer post-hoc test in shared Methods — Figure 8 image/caption; Results Sec21; Methods Sec10 and Sec12

In Vivo Studies

In athymic nude mice, DHTS at 10 mg/kg intraperitoneally every 48 hours reduced parental HCT116 xenograft growth. HuR-knockout tumors grew more slowly and showed no significant DHTS response. The small experiment used three mice per group with two tumors per mouse; altered drug uptake after HuR loss remained a possible confound identified by the authors. [2]

HuR-dependent tumor response in HCT116 xenografts

Animal study · Six-week-old athymic nude (Nu/Nu) mice bearing subcutaneous parental HCT116 or HuR-knockout HCT116 tumors [2]

DHTS reduced growth of parental HCT116 xenografts, with an approximately fourfold reduction in tumor size reported by the authors. HuR-knockout tumors grew more slowly and showed no significant response to DHTS in Figure 5C. The experiment used three mice per group, with two tumors per mouse; tumors are not six independent animals.

Measured endpoints — not treatment concentrations
Endpoint	Reported result	Reference
Tumor growth in parental and HuR-knockout HCT116 xenografts	Reported relative tumor-size response Approximately 4-fold reduction in parental tumor size; no significant knockout response	[2]

Conditions shared by the study groups

Route: Intraperitoneal
Frequency: Every 48 h
Treatment course: Follow-up to day 31; exact dosing-start date not established.
Vehicle: PBS/5% N-methyl pyrrolidine (NMP), as reported

Study groups and reported outcomes
Group / dose	Comparator	Observed result	Reference
Parental HCT116 xenografts + DHTS 10 mg/kg	Same-genotype xenografts treated with vehicle	Growth inhibited versus matched vehicle; authors report approximately 4-fold smaller tumors.	[2]
HCT116ΔHuR xenografts + DHTS 10 mg/kg	Same-genotype xenografts treated with vehicle	Slower basal growth than parental tumors; DHTS-versus-vehicle difference not significant in Figure 5C.	[2]

Parental HCT116 xenografts + DHTS: Model: Parental HCT116 xenografts; Reported limits: Sex and randomization/blinding not specified in the selected Methods; three mice per group with two tumors per mouse.

HCT116ΔHuR xenografts + DHTS: Model: HCT116ΔHuR xenografts; Reported limits: Sex and randomization/blinding not specified in the selected Methods; three mice per group with two tumors per mouse.

Methods and source locations

Compound reported in the paper: Dihydrotanshinone I; Compound label in the paper: DHTS

Compound-level research evidence; tested material and model remain study-specific.

Methods SEC2-1 and SEC2-2; Results SEC3-7; Figure 5C-D; Discussion paragraph on immune model and uptake

Tumor growth in parental and HuR-knockout HCT116 xenografts: Caliper-derived volumes measured three times weekly; Figure 5C ***p < 0.001 for parental response and n.s. for knockout comparison; three mice/group, two tumors/mouse — Results SEC3-7; Figure 5C-D; Methods SEC2-2

Parental HCT116 xenografts + DHTS · Methods SEC2-1 and SEC2-2; Results SEC3-7; Figure 5C-D; Discussion paragraph on immune model and uptake

HCT116ΔHuR xenografts + DHTS · Methods SEC2-1 and SEC2-2; Results SEC3-7; Figure 5C-D; Discussion paragraph on immune model and uptake

Specifications

Manufacturer	Adooq Bioscience
CAS Number	87205-99-0
Formula	C₁₈H₁₄O₃
Molecular Weight	278.3
SMILES	CC1COC2=C1C(=O)C(=O)C3=C2C=CC4=C3C=CC=C4C

Storage & Solubility

In Vitro Solubility

Reported Solubility

Solvent	Reported Solubility
DMSO	3 mg/mL (10.78 mM)

Preparing Stock Solutions

Stock preparation is unavailable for this product molecular weight.

Calculated stock concentrations do not establish solvent solubility. Refer to the reported solubility data for experimental guidance.

Storage

Store powder at -20°C, keep desiccated.
In powder form, the chemical is stable for 36 months.
In solution, store at -20°C and use within 1 month to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.

Research References

[1] D'Agostino VG, Lal P, Mantelli B, et al. Dihydrotanshinone-I interferes with the RNA-binding activity of HuR affecting its post-transcriptional function Scientific reports (2015). PMID: 26553968 DOI: 10.1038/srep16478 Source material
[2] Lal P, Cerofolini L, D'Agostino VG, et al. Regulation of HuR structure and function by dihydrotanshinone-I Nucleic acids research (2017). PMID: 28934484 DOI: 10.1093/nar/gkx623 Source material
[3] Shatat AS, Mahgoup EM, Rashed MH, et al. Molecular mechanisms of extracellular-ATP-mediated colorectal cancer progression: Implication of purinergic receptors-mediated nucleocytoplasmic shuttling of HuR Purinergic signalling (2024). PMID: 38801618 DOI: 10.1007/s11302-024-10021-2 Source material

Publications

1 publication citing this product

Abdel-Aziz S Shatat, .et al. , Purinergic Signal, 2024, May 27 PMID: 38801618

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Dihydrotanshinone I

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