Tenacigenin B derivatives reverse P-glycoprotein-mediated multidrug resistance inHepG2/Dox cells.
Tenacissimoside A (1) and 11alpha-O-benzoyl-12beta- O-acetyltenacigenin B (2), two derivatives of tenacigenin B (3) from the plant Marsdenia tenacissima, reversed multidrug resistance in P-glycoprotein (Pgp)-overexpressing multidrug-resistant cancer cells. The sensitivity of HepG2/Dox cells to the antitumor drugs doxorubicin, vinblastine, puromycin, and paclitexel was increased by 18-, 10-, 11-, and 6-fold by 20 microg/mL (or 25 microM) of 1 and 16-, 53-, 16-, and 326-fold by 20 microg/mL (or 39 microM) of 2, respectively. A preliminary mechanistic study has suggested that 1 might modulate Pgp-mediated multidrug resistance through directly interacting with the Pgp substrate site.
Research Group of Pharmaceutical Sciences, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, People's Republic of China. yingjiehu@163.net
Ying-Jie
YJ
Hu
Xiao-Ling
XL
Shen
Hong-Long
HL
Lu
Yu-Hu
YH
Zhang
Xin-An
XA
Huang
Lin-Chun
LC
Fu
Wang-Fun
WF
Fong
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D006801:Humans; D031101:Marsdenia / Q000737:chemistry*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D011691:Puromycin / Q000494:pharmacology; D013256:Steroids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D004317:Doxorubicin; D004365:Drugs, Chinese Herbal; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D017239:Paclitaxel; D011691:Puromycin; D013256:Steroids; D014747:Vinblastine; C531263:11alpha-O-benzoyl-12beta-O-acetyltenacigenin B; C531264:tenacigenin B; C531262:tenacissimoside A