Propafenone

Propafenone (SA-79), a sodium-channel blocker, acts an antiarrhythmic agent. Propafenone also has high affinity for the β receptor (IC50=32 nM)[1]. Propafenone blocks the transient outward current (Ito) and the sustained delayed rectifier K current (Isus) with IC50 values of 4.9 μm and 8.6 μm, respectively[2]. Propafenone suppresses esophageal cancer proliferation through inducing mitochondrial dysfunction and induce apoptosis[3].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Cancer

Research Areas >> Cardiovascular Disease

Signaling Pathways >> GPCR/G Protein >> Adrenergic Receptor

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Propafenone (5-25 μM) inhibits esophageal squamous cell carcinoma (ESCC) cell proliferation[3]. Propafenone causes mitochondrial dysfunction by a decreased mitochondrial membrane potential and reduced expression of Bcl-xL and Bcl-2[3]. Propafenone (10 and 20 μm) treatment significantly down regulates the expression levels of the anti-apoptotic proteins Bcl-xL and Bcl-2 in ESCC cells. Propafenone also reduces expression of p-ERK[3]. Cell Proliferation Assay[3] Cell Line: The human ESCC cell lines KYSE30, KYSE150 and KYSE270 Concentration: 5, 10, 15, 20, and 25 μm Incubation Time: 24, 48, and 72 hours Result: Gradually decreased cell proliferation over time and potently inhibited cell proliferation with increasing concentrations in KYSE30, KYSE150 and KYSE270 cells. Western Blot Analysis[3] Cell Line: The human ESCC cell lines KYSE30, KYSE150 and KYSE270 Concentration: 0, 10, and 20 μm Incubation Time: 72 hours Result: Significant downregulation of Bcl-xL and Bcl-2 expression levels was observed.

Propafenone (20 mg/kg; intraperitoneal injection every other day) markedly suppresses the tumor burden with a decrease of 69.2%[3]. Propafenone also significantly inhibits tumor cell proliferation (mean index decreased from 56.3±6.7% in the DMSO-treated group to 20.7±5.1% in the 10 mg/kg propafenone-treated group and 11.3±4.0% in the 20 mg/kg propafenone-treated group)[3]. Animal Model: Female BALB/c nude mice bearing KYSE270-derived xenografts (6-8 weeks)[3] Dosage: 10 mg/kg or 20 mg/kg Administration: Intraperitoneally injected Result: Exerted a significantly inhibitory effect on the growth of tumor xenografts.

[1]. J T Lee, et al. The role of genetically determined polymorphic drug metabolism in the beta-blockade produced by propafenone. N Engl J Med. 1990 Jun 21;322(25):1764-8.

[2]. A Seki, et al. Effects of propafenone on K currents in human atrial myocytes. Br J Pharmacol. 1999 Mar;126(5):1153-62.

[3]. Wei-Bin Zheng, et al. Propafenone suppresses esophageal cancer proliferation through inducing mitochondrial dysfunction. Am J Cancer Res. 2017 Nov 1;7(11):2245-2256.

MOLECULAR FORMULA :

C21-H27-N-O3

MOLECULAR WEIGHT :

341.49

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

36 mg/kg/3D-I

TOXIC EFFECTS :

Behavioral - hallucinations, distorted perceptions Behavioral - toxic psychosis Behavioral - alteration of classical conditioning

REFERENCE :

JCLPDE Journal of Clinical Psychiatry. (Physicians Postgraduate Press, Inc., POB 240008, Memphis, TN 38124) V.39- 1978- Volume(issue)/page/year: 46,104,1985

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

2346 mg/kg/1Y-I

TOXIC EFFECTS :

Peripheral Nerve and Sensation - sensory change involving peripheral nerve

REFERENCE :

MACPAJ Mayo Clinic Proceedings. (Room 1035, Plummer Bldg., Mayo Clinic, Rochester, MN 55905) V.39- 1964- Volume(issue)/page/year: 70,469,1995

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - woman

DOSE/DURATION :

1404 mg/kg/78D-I

TOXIC EFFECTS :

Skin and Appendages - dermatitis, allergic (after systemic exposure)

REFERENCE :

AIMEAS Annals of Internal Medicine. (American College of Physicians, 4200 Pine St., Philadelphia, PA 19104) V.1- 1927- Volume(issue)/page/year: 104,589,1986

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human - man

DOSE/DURATION :

116 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - coma Cardiac - EKG changes not diagnostic of specified effects

REFERENCE :

AEMED3 Annals of Emergency Medicine. (American College of Emergency Physicians, 1125 Executive Circle, Irving, TX 75038) Volume(issue)/page/year: 24,98,1994

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

440 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JJTOEX Japanese Journal of Toxicology. (Yakugyo Jihosha, Hokushin Bldg., 2-36 Jinbo-cho, Kanda, Chiyoda-ku, Tokyo, 101, Japan) V.1- 1988- Volume(issue)/page/year: 4,121,1991