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REVIEW Podophyllotoxin's anticancer property can be attributed to the inhibition of tubulin polymerization. As podophyllotoxin binds to the tubulin, microtubule formation is prevented. Consequently, podophyllotoxin arrests the cell cycle in the metaphase. Podophyllotoxin derivatives display binding activity to the enzyme topoisomerase II during the late S and early G2 stage. For instance, etoposide binds and stabilizes the temporary break caused by the enzyme, disrupts the reparation of the break through which the double-stranded DNA passes, and consequently stops DNA unwinding and replication. Mutants resistant to either podophyllotoxin, or to its topoisomerase II inhibitory derivatives such as etoposide (VP-16), have been described in Chinese hamster cells. The mutually exclusive cross-resistance patterns of these mutants provide a highly specific mean to distinguish the two kinds of podophyllotoxin derivatives. Mutant Chinese hamster cells resistant to podophyllotoxin are affected in a protein P1 that was later identified as the mammalian HSP60 or chaperonin protein.
REFERENCES
[1]
Gensler, Walter J.; Johnson, Francis Compounds related to podophyllotoxin. XIV. Isopodophyllotoxin and epiisopodophyllotoxin Journal of the American Chemical Society (1963), 85(22), 3670-3.
[2]
Yamaguchi, Hideo; Arimoto, Masao; Nakajima, Syunji; Tanoguchi, Mariko; Fukada, Yoshinari Studies on the constituents of the seeds of Hernandia ovigera L. V. Syntheses of epipodophyllotoxin and podophyllotoxin from desoxypodophyllotoxin Chemical & Pharmaceutical Bulletin (1986), 34(5), 2056-60.
[3]
Kaneko, Takushi; Wong, Henry S. L Preparation of the antineoplastic agent podophyllotoxin and intermediates thereof Eur. Pat. Appl. (1987), EP 224938 A2 19870610.
[4]
Gupta, R.S., Ho, T.K.W., Moffat, M.R.K. and Gupta, R. (1982). Podophyllotoxin-resistant mutants of Chinese hamster ovary cells. Alteration in a microtubule-associated protein. J. Biol. Chem. 257: 1071-1078.
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