title: Antitumor activity of liposomal naphthoquinone esters isolated from Thai medicinal plant: Rhinacanthus nasutus KURZ.
abstract: We previously observed that rhinacanthins-C, -N and -Q, three main naphthoquinone esters isolated from the roots of Thai medicinal plant; Rhinacanthus nasutus KURZ. (Acanthaceae) induced apoptosis of human cervical carcinoma HeLaS3 cells. Since these rhinacanthins showed limited solubility in aqueous medium, we attempted to entrap them into liposomal membrane: Liposomalization enabled injection of the drugs and the drugs were expected to transfer to lipoproteins in the bloodstream. Liposomal formulations of rhinacanthins-C, -N and -Q showed strong antiproliferative activity against HeLaS3 cells with the IC50 values of 32, 17, 70 microM; 19, 17, 52 microM and 2.7, 2.0 and 5.0 microM for the exposure time of 24, 48, and 72 h, respectively. These liposomes suppressed the tumor growth in Meth-A sarcoma-bearing BALB/c mice at the dose of 5.0 mg/kg/d for 10 d. Among rhinacanthins, liposomal rhinacanthin-N significantly suppressed solid tumor growth. Based on these results, our findings demonstrated that rhinacanthin-N suppressed tumor growth in vivo, and suggested that liposomes are useful for preparing injectable formulation of hydrophobic drugs.
authors.affiliation: Natural Products Research Section, Research Division, National Cancer Institute, Bangkok, Thailand.
authors.forename: Pongpun
authors.initials: P
authors.lastname: Siripong
authors.forename: Jantana
authors.initials: J
authors.lastname: Yahuafai
authors.forename: Kosuke
authors.initials: K
authors.lastname: Shimizu
authors.forename: Kanae
authors.initials: K
authors.lastname: Ichikawa
authors.forename: Sei
authors.initials: S
authors.lastname: Yonezawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Asai
authors.forename: Kwanjai
authors.initials: K
authors.lastname: Kanokmedakul
authors.forename: Somsak
authors.initials: S
authors.lastname: Ruchirawat
authors.forename: Naoto
authors.initials: N
authors.lastname: Oku
mesh_terms: D027901:Acanthaceae / Q000737:chemistry*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001201:Ascites / Q000473:pathology / Q000517:prevention & control; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004952:Esters; D006367:HeLa Cells; D006801:Humans; D017705:Lignans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008081:Liposomes; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015394:Molecular Structure; D009285:Naphthoquinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009368:Neoplasm Transplantation / Q000379:methods; D008517:Phytotherapy / Q000379:methods; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D018517:Plant Roots / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*; D012513:Sarcoma, Experimental / Q000473:pathology / Q000517:prevention & control; D016019:Survival Analysis; D013785:Thailand
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004952:Esters; D017705:Lignans; D008081:Liposomes; D009285:Naphthoquinones; D010936:Plant Extracts; C515072:rhinacanthin-N