Methyl protodioscin  (Synonyms: NSC-698790; Smilax saponin B)

Methyl protodioscin (NSC-698790; Smilax saponin B) is a multi-target, selective, steroidal diglycoside inhibitor with antitumor activity that induces cell cycle arrest. The mechanism of action of Methyl protodioscin is complex, involving the induction of G2/M cell cycle arrest, regulation of the Bcl-2/Bax apoptotic pathway, inhibition of the Akt1/c-Myc axis and MAPK/ERK signaling, while simultaneously downregulating ADAM15 and inducing FOXO1 to reduce cholesterol synthesis. It also inhibits the JNK/c-Jun pathway, reducing the production of inflammatory factors (IL-6, TNF-α). Methyl protodioscin exhibits significant antitumor (inhibiting proliferation, migration, invasion, and inducing apoptosis), anti-inflammatory, and anti-restenosis activities. Methyl protodioscin can be used in research on lung cancer, prostate cancer, pancreatic cancer, and other tumors, as well as inflammatory diseases such as airway inflammation and enteritis^{[1][2][3][4][5][6][7]}.

Methyl protodioscin (10 nM-0.1 μM; 48 h) was screened in vitro against 60 human cancer cell lines, showing strong cytotoxicity against most solid tumor cells (GI₅₀ ≤ 10.0 μM), with the strongest selectivity against colon cancer cells HCT-15 (GI₅₀ = 1.93 μM) and breast cancer cells MDA-MB-435 (GI₅₀ = 1.69 μM), and moderate toxicity against leukemia cells (GI₅₀ 10-30 μM); the GI₅₀ values ??of methyl protodioscin against various tumor cells ranged from 1.69 to 50 μM (e.g., MDA-MB-435: 1.69 μM, DU145: approximately 4 μM), and the IC₅₀ against vascular smooth muscle cells A7r5 was approximately 9 μM^[1].
Methyl protodioscin (5-20 μM; 48 h) dose-dependently inhibited proliferation in A549 lung cancer cells, inducing G2/M phase cell cycle arrest and apoptosis, downregulating Bcl-2 expression, upregulating Bax expression, activating caspase-3, reducing mitochondrial membrane potential, and promoting cytochrome c release^[2].
Methyl protodioscin (1-10 μM; 24-48 h) inhibited proliferation (48-hour IC₅₀ approximately 4 μM), migration, and invasion in DU145 prostate cancer cells, inducing G2/M phase arrest and apoptosis, downregulating SREBP1, SREBP2, and HMGCR mRNA expression, upregulating ABCA1 and FOXO1 protein expression, and inhibiting P-ERK activity^[3].
Methyl protodioscin (15-50 μM; 24-48 h) in PANC-1 (IC₅₀ = 34.4 μM) and MIA PaCa-2 (IC₅₀ = 50 μM) In pancreatic cancer cells, methyl protodioscin inhibits proliferation, induces G2/M phase arrest and apoptosis, downregulates the expression of glycolysis-related genes Glut1, HK2, LDHA, and PDK1, and inhibits the Akt1/c-Myc signaling pathway^[4].
Methyl protodioscin (1-100 ng/mL; 12-48 h) repairs inflammation-induced barrier function damage in Caco-2 intestinal epithelial cells, promotes crypt formation in mouse intestinal crypt cultures (10 ng/mL being optimal), and upregulates RegIIIc mRNA expression^[5].
Methyl protodioscin (3-9 μM; 16-24 h) inhibits proliferation (IC₅₀ approximately 9 μM) and migration in A7r5 vascular smooth muscle cells, induces G0/G1 phase arrest, and downregulates the protein expression and activity of ADAM15, P-FAK, P-ERK, and MMP-2/9^[6].
Methyl protodioscin (10-100 μM; 4 h) inhibits IL-1β-induced IL-6, IL-8, and TNF-α production in A549 cells and inhibits JNK/c-Jun activation; 100 μM treatment of MH-S macrophages for 24 hours slightly inhibits NO production, but this is accompanied by slight cytotoxicity^[6].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Methyl protodioscin (0.5 mg/kg, 1 mg/kg; tail vein injection; once daily; 15 days) significantly reduced tumor volume and weight, decreased cholesterol concentration in tumor tissue, induced FOXO1 expression, inhibited P-ERK activity, upregulated Bax, cleaved caspase-3, and cleaved PARP expression, downregulated Bcl-2 expression, and promoted tumor cell apoptosis in a subcutaneous prostate cancer RM-1 cell xenograft model in male C57BL/6 mice^[3].
Methyl protodioscin (100 mg/kg; intravenous injection; frequency and duration not specified) inhibited tumor growth, reduced ¹⁸F-FDG uptake in tumor tissue, and inhibited glycolysis in vivo in a subcutaneous pancreatic cancer MIA PaCa-2 cell xenograft model in BALB/c-nu mice^[4].
Methyl protodioscin (25 mg/kg; intraperitoneal injection; once daily; 5 days/10 days) increased the survival rate of 4% DSS-induced mice, promoted mucosal healing in 2.5% DSS-induced mice, reduced colon inflammation scores, decreased NF-κB activation and inflammatory cytokine (TNF-α, IL-17, IL-23) production, and reduced bacterial translocation to mesenteric lymph nodes in a DSS (HY-116282C)-induced colitis model in C57BL/6 mice^[5].
Methyl protodioscin (25 mg/kg; intraperitoneal injection; once daily; 7 days) alleviated colon inflammation, reduced bacterial colonization and translocation to mesenteric lymph nodes, and restored body weight and colon length in a Citrobacter rodentium infection-induced colitis model in C57BL/6 mice^[5].
Methyl protodioscin (3 μM, 6 μM; topical application; single administration; 2 weeks) significantly reduced neointimal formation, decreased the neointima/media area ratio, and downregulated ADAM15 in vascular tissue in a carotid artery balloon injury model in male rats^[6].
Protein expression^[6].
Methyl protodioscin (30 mg/kg, 60 mg/kg; oral administration; single dose; 16 h) reduced total cell and neutrophil/macrophage infiltration in bronchoalveolar lavage fluid, decreased mRNA expression of IL-6, IL-1β, and TNF-α in lung tissue, and improved pathological changes such as alveolar wall thickening and alveolar lumen narrowing in a LPS-induced acute lung injury model in male ICR mice^[7].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

1063.23

C₅₂H₈₆O₂₂

54522-52-0

Solid

White to off-white

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Room temperature in continental US; may vary elsewhere.

4°C, protect from light

*In solvent : -80°C, 6 months; -20°C, 1 month (protect from light)

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (protect from light). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

• [1]. Hu K, et al. The cytotoxicity of methyl protodioscin against human cancer cell lines in vitro. Cancer Invest. 2003 Jun;21(3):389-93.  [Content Brief]

  [2]. Bai Y, et al. Methyl protodioscin induces G2/M cell cycle arrest and apoptosis in A549 human lung cancer cells. Pharmacogn Mag. 2014 Jul;10(39):318-24.  [Content Brief]

  [3]. Chen J, et al. Anticancer Activity of Methyl Protodioscin against Prostate Cancer by Modulation of Cholesterol-Associated MAPK Signaling Pathway via FOXO1 Induction. Biol Pharm Bull. 2023;46(4):574-585.  [Content Brief]

  [4]. Chen L, et al. Natural Compound Methyl Protodioscin Suppresses Proliferation and Inhibits Glycolysis in Pancreatic Cancer. Evid Based Complement Alternat Med. 2018 Mar 15;2018:7343090.  [Content Brief]

  [5]. Zhang R, et al. Natural compound methyl protodioscin protects against intestinal inflammation through modulation of intestinal immune responses. Pharmacol Res Perspect. 2015 Mar;3(2):e00118.  [Content Brief]

  [6]. Chung YL, et al. Methyl Protodioscin, a Steroidal Saponin, Inhibits Neointima Formation in Vitro and in Vivo. J Nat Prod. 2016 Jun 24;79(6):1635-44.  [Content Brief]

  [7]. Lee JH, et al. Methyl Protodioscin from the Roots of Asparagus cochinchinensis Attenuates Airway Inflammation by Inhibiting Cytokine Production. Evid Based Complement Alternat Med. 2015;2015:640846.  [Content Brief]