Antitumor Activity of Liposomal Naphthoquinone Esters Isolated from Thai Medicinal Plant: Rhinacanthus nasutus KURZ.

Abstract

Rhinacanthus nasutus KURZ. (family Acanthaceae), has been used in Thai traditional medicine for the treatment of various diseases such as eczema, pulmonary tuberculosis, herpes, hepatitis, diabetes, hypertension and various skin diseases, and its active components were widely investigated. 1-7)R. nasutus KURZ. has also been used for cancer treatment. [8][9][10] The main bioactive compounds were revealed to be naphthoquinone; rhinacanthins (A-D, G-Q), rhinacanthone and lignan groups. [1][2][3][4][5][6][7][8]10,11) Antitumor activity of R. nasutus KURZ. extracts,8) and that of rhinacanthone in the in vivo study were reported. 11) We previously reported that rhinacanthins-M, -N and -Q and related naphthoquinone esters as well as synthetic compounds, 1,2-naphthoquinones and 1,4-naphthoquinones, selectively suppressed the growth of KB, HeLa and HepG2 human cancer cells, and normal Vero cells. 12,13) We also performed mechanistic study and observed that synthetic rhinacanthins-N and -Q inhibited DNA topoisomerase II.13) A naphthoquinone compound b-lapachone, that was also derived from natural products and has a similar structure to rhinacanthone, was reported to be a potent inhibitor of DNA topoisomerase I and II, [14][15][16] and to induce apoptosis of various cancer cells. [17][18][19][20][21] Recently, we observed that rhinacanthins-C, -N and -Q suppressed human cervical carcinoma HeLaS3 cells through induction of apoptosis. 22)Therefore, in the present study, we attempted to determine actual antitumor activity of rhinacanthins in tumor-bearing mice.Since rhinacanthins-C, -N and -Q are hydrophobic compounds, they are not able to inject into bloodstream without solubilization. For in vivo use of the drugs, we attempted to solubilize them in liposomes. By the way, liposomes have been widely used in the field of drugs delivery systems (DDS): Liposomalization reduces side effects and toxicities of drugs encapsulated, and improves their bioavailability. Therefore, liposomes tended to be used for cancer treatment, since most of anticancer drugs accompany severe side effects. [23][24][25] Furthermore, liposomes with long circulating characteristics are known to accumulate in interstitial spaces of tumor tissues of which blood vessels are highly permeable. 26,27) For the purpose of DDS, liposomes having rather rigid lipid bilayer are favorable, and they are usually composed of phospholipids with saturated fatty acyl chains and cholesterol. On the other hand, liposomes have been used for the injection of hydrophobic drugs, since hydrophobic materials can be encapsulated into the lipid bilayer of the liposomes. For example, Visudyne, a liposomal formulation of benzoporphyrin derivative monoacid ring A (BPD-MA), is being used clinically in photodynamic therapy for age-related macular degeneration. In Visudyne, liposomes are used as a "solvent" of BPD-MA for the purpose of injection of the drug into bloodstream.28) In such case, liposomes having rather fluid lipid bilayer are used, and the injected drug in the bloodstream is t...

Roles of Plant Extracts and Constituents in Cervical Cancer Therapy

“…The same group have also shown that when these naphthoquinone esters are liposomalized with egg yolk phosphatidylcholine (EPC) and egg yolk phosphatidylglycerol (EPG), there was significant increase in the antiproliferative effects on HeLa cells as measured by cell proliferation assay (Siripong et al, 2006b). The proliferation of the cells was significantly inhibited by rhinacanthins when the concentration of these drugs was increased from 3-300 mM and the exposure time was prolonged to 24-72 h. The IC 50 values of rhinacanthins-C, -N and -Q were 32, 17 and 70 mM for 24 h; 19, 17 and 52 mM for 48 h; and 2.7, 2.0 and 5.0 mM for 72 h incubation, respectively.…”

Ethyl acetate extract fromGlycosmis parvaleaf induces apoptosis and cell-cycle arrest by decreasing expression of COX-2 and altering BCL-2 family gene expression in human colorectal cancer HT-29 cells

“…Major attention has been focused on identifying phytochemicals that can inhibit tumor development processes (Siripong et al, 2006(Siripong et al, , 2009. Glycosmis parva Craib (Rutaceae) is a wild small shrub found in Thailand.…”

Anti-oxidant properties and anti-hemolytic activity of Psidium guajava, Pandanous odorus and Rhinacanthus nasutus

“…Siripong and coworkers reported that among rhinacanthins, rhinacanthin-N significantly suppressed tumor growth in vivo (Siripong et al, 2006). It has been reported that rhinacanthone isolated from R. nasutus roots induced apoptosis in human cervical carcinoma cells (Siripong et al, 2009).…”