Effects of taxoids from Taxus cuspidata on microtubule depolymerization and vincristine accumulation in MDR cells

Kobayashi, Jun’ichi; Hosoyama, Hirokazu; Wang, Xiaoxia; Shigemori, Hideyuki; Koiso, Yukiko; Iwasaki, Shigeo; Sasaki, Takuma; Naito, Mikihiko; Tsuruo, Takashi

doi:10.1016/s0960-894x(97)00029-2

Cited by 50 publications

(29 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, compounds 1, 2, and 3 reduced the binding activity of P-gp with azidopine in multidrug-resistant 2780AD cells as well as verapamil, while compound 4 and taxol (6) were inactive. 5) These results suggest that taxoids (1, 2, and 3) bind to the same site as that of azidopine to P-gp. Recently, we found that taxuspine C (1) given i.p.…”

Section: Discussionmentioning

confidence: 80%

“…4,5) More recently, we found that taxuspine C (1) enhanced the chemotherapeutic effect of VCR in VCR-resistant murine leukemia P388/VCR-bearing mice. 6) In this paper, we report that the non-taxol-type taxoids 1-3 showed remarkable MDR reversal activity on colchicine-resistant human epidermoid carcinoma KB-C2 cells, which overexpress P-gp, when co-administered with colchicine, VCR, or taxol.…”

mentioning

confidence: 95%

See 1 more Smart Citation

Multidrug Resistance Reversal Activity of Taxoids from Taxus cuspidate in KB‐C2 and 2780AD Cells

Kobayashi

Shigemori

Hosoyama

et al. 2000

Japanese Journal of Cancer Research

Self Cite

View full text Add to dashboard Cite

Some non-taxol-type taxoids having neither an oxetane ring at C-4 and C-5 nor an N-acylphenylisoserine group at C-13, such as taxuspine C, 2′ ′ ′ ′-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J, which were isolated from the Japanese yew Taxus cuspidata, increased cellular accumulation of vincristine (VCR) in multidrug-resistant 2780AD cells as potently as verapamil, and efficiently inhibited [ 3 H]azidopine photolabeling of P-glycoprotein (P-gp). Taxuspine C, 2′ ′ ′ ′-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J at 10 µ µ µ µM completely reversed the resistance to colchicine, VCR, and taxol in KB-C2 cells, which overexpress P-gp, while taxinine and taxinine M showed no effect. Taxuspine C, 2′ ′ ′ ′-desacetoxyaustrospicatine, and 2-desacetoxytaxinine J may be candidate pharmaceuticals for reversing multidrug resistance (MDR) and also may be good modifiers of MDR in cancer chemotherapy.

show abstract

Section: Discussionmentioning

confidence: 80%

mentioning

confidence: 95%

Multidrug Resistance Reversal Activity of Taxoids from Taxus cuspidate in KB‐C2 and 2780AD Cells

Kobayashi

Shigemori

Hosoyama

et al. 2000

Japanese Journal of Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…These results suggested that many taxoids could be substrates of P-glycoprotein and some of them might be useful for overcoming multidrug resistance. 31,[35][36][37] …”

Section: Increased Cellular Accumulation Of Vincristine In Multidrmentioning

confidence: 99%

Bioactive taxoids from the Japanese yew Taxus cuspidata

Kobayashi

Shigemori

2002

Medicinal Research Reviews

Self Cite

View full text Add to dashboard Cite

A series of new taxoids, named taxuspines A-H and J-Z (1-25) and taxezopidines A-H and J-L (26-36), have been isolated together with 37 known taxoids (37-73) including paclitaxel (53) from the Japanese yew, Taxus cuspidata Sieb. et Zucc. (Taxaceae). These new taxoids possess various skeletons containing 5/7/6, 6/10/6, 6/5/5/6, 6/8/6, or 6/12-membered ring systems. Among the new taxoids, some non-taxol-type compounds remarkably reduced CaCl(2)-induced depolymerization of microtubules, or increased cellular accumulation of vincristine in multidrug-resistant tumor cells as potent as verapamil. On the other hand, chemical derivatization of taxinine (37), one of major taxoids obtained from this yew, led to the discovery of unusual reactions of taxinine derivatives. Here we describe our recent results on the isolation, structure elucidation, and bioactivity of these new and known taxoids and the formation of unexpected products of the unusual reactions of taxinine.

show abstract

“…Stimulated by the interesting results on the photoaffinity labeling of P-GP with BzDC-paclitaxel analogs and from reports that some noncytotoxic natural taxanes were increasing the accumulation of the anticancer drug vincristine in MDR tumor cells (24,25), we have developed a range of "taxane MDR reversal agents (TRAs)" based on the baccatin III skeleton, which is a crucial component of paclitaxel and other taxane anticancer agents, modified with BzDC, Bz-Cinnamoyl, and other planar hydrophobic group(s) at the C-7 and C-10 positions (26). Several of these compounds exhibited excellent MDR-reversal activities when co-administered with paclitaxel, which were better than those of verapamil and cyclosporine A against both LCC6-MDR and MCF7-MDR cell lines.…”

Section: Overcoming P-gp-related Multidrug Resistance (Mdr)mentioning

confidence: 99%

Medicinal Chemistry and Chemical Biology of New Generation Taxane Antitumor Agents

et al. 2002

View full text Add to dashboard Cite

show abstract

Effects of taxoids from Taxus cuspidata on microtubule depolymerization and vincristine accumulation in MDR cells

Cited by 50 publications

References 7 publications

Multidrug Resistance Reversal Activity of Taxoids from Taxus cuspidate in KB‐C2 and 2780AD Cells

Multidrug Resistance Reversal Activity of Taxoids from Taxus cuspidate in KB‐C2 and 2780AD Cells

Bioactive taxoids from the Japanese yew Taxus cuspidata

Medicinal Chemistry and Chemical Biology of New Generation Taxane Antitumor Agents

Contact Info

Product

Resources

About