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.
Hu
Ying-Jie
YJ
Research Group of Pharmaceutical Sciences, Tropical Medicine Institute, Guangzhou University of Chinese Medicine, Guangzhou 510405, People's Republic of China. yingjiehu@163.net
Shen
Xiao-Ling
XL
Lu
Hong-Long
HL
Zhang
Yu-Hu
YH
Huang
Xin-An
XA
Fu
Lin-Chun
LC
Fong
Wang-Fun
WF
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