title: Involvement of substance p/neurokinin-1 receptor in the analgesic and anticancer activities of minimally toxic fraction from the traditional Chinese medicine Liu-Shen-Wan in vitro.
abstract: Liu-Shen-Wan (LSW), an ancient preparation used to treat localized infection with pain, was recently reported to possess anticancer activity. The mechanism responsible for LSW's analgesic and anticancer activity is unclear. In the present study, we obtained a LSW supernatant (LSWS) fraction from ultrasound-assisted ethanol extraction (yield 15.9%) which proved to be safer than LSW in terms of hepatotoxicity. The LSWS (1 and 10 µg/mL) exhibited a potent inhibitory effect on the bradykinin-evoked rapid release of substance P from dorsal root ganglion (DRG) cells. At concentrations of 0.1 µg/mL and higher, the LSWS resulted in a concentration-related growth inhibitory effect on HepG2, a representative cancer cell lines. The LSWS significantly down-regulated the neurokinin-1 (NK-1) receptor expression in both HepG2 and bradykinin-treated DRG cells. In addition to the NK-1 receptor-dependent growth inhibition in HepG2 cells (0.1-100 µg/mL), the LSWS induced mitochondria-mediated apoptosis at a higher concentration (1-100 µg/mL). In conclusion, we recently isolated a safer LSW fraction which maintained its analgesic and anticancer activity, and found that the substance P/NK-1 receptor system was partly responsible for these effects. Our findings will be useful for developing more effective and less toxic LSW preparations.
authors.affiliation: Department of Pharmacology, College of Pharmacy, South-Central University for Nationalities.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Li
authors.forename: Mei-Mei
authors.initials: MM
authors.lastname: Jia
authors.forename: Yu-Sang
authors.initials: YS
authors.lastname: Li
authors.forename: Yan-Ling
authors.initials: YL
authors.lastname: Yang
authors.forename: Xian-Qing
authors.initials: XQ
authors.lastname: Mao
authors.forename: He-Bin
authors.initials: HB
authors.lastname: Tang
mesh_terms: D000700:Analgesics / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis; D001920:Bradykinin / Q000494:pharmacology; D045424:Complex Mixtures / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005727:Ganglia, Spinal / Q000187:drug effects; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D008928:Mitochondria / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism*; D008517:Phytotherapy; D018040:Receptors, Neurokinin-1 / Q000378:metabolism*; D013373:Substance P / Q000378:metabolism*
chemical_list: D000700:Analgesics; D000970:Antineoplastic Agents; D045424:Complex Mixtures; C513610:Liu-Shen-Wan; D018040:Receptors, Neurokinin-1; D013373:Substance P; D001920:Bradykinin