Method for increasing sensitivity to chemically induced terminal differentiation

DETAILED DESCRIPTION OF THE INVENTION The present invention provides a method of selectively inducing terminal differentiation of neoplastic cells and thereby inhibiting proliferation of such cells which comprises treating the cells so as to render them resistant to an antitumor agent and contacting the resulting resistant cells under suitable conditions with an amount of a compound effective to selectively induce terminal differentiation of such cells.
The compound has a structure: [R-A]-B-[A.
sub.
1 -B.
sub.
1 -].
sub.
a [A.
sub.
2 -B.
sub.
2 -].
sub.
b [A.
sub.
3 -R.
sub.
1 ] wherein each of A, A.
sub.
1, A.
sub.
2, and A.
sub.
3 represent a polar group which comprises a nitrogen, sulfur or oxygen atom and wherein each of A, A.
sub.
1, A.
sub.
2, and A.
sub.
3 may independently be the same as, or different from, the others of A, A.
sub.
1, A.
sub.
2, and A.
sub.
3 ; wherein each of R and R.
sub.
1 is a hydrogen atom; a lower alkyl, alkenyl, or alkynyl group; or a group having the structure: ##STR2## each R.
sub.
2 and R.
sub.
3 being a hydrogen atom or a lower alkyl, alkenyl, or alkynyl group; and wherein each of R, R.
sub.
1, R.
sub.
2 and R.
sub.
3 may independently be the same as, or different from, the others of R, R.
sub.
1, R.
sub.
2, and R.
sub.
3 ; wherein each [R-A] and [A.
sub.
3 -R.
sub.
1 ] have a dipolar moment greater than about 2.
7 Debye units; wherein each of B, B.
sub.
1, and B.
sub.
2 represents a nonpolar group which comprises at least 4 atoms in a chain, the termini of which chains are attached to A and A.
sub.
1, A.
sub.
1 and A.
sub.
2, and A.
sub.
2 and A.
sub.
3 respectively; wherein each such atom is oxygen, nitrogen, carbon, or sulfur and wherein each of B, B.
sub.
1, and B.
sub.
2 may independently be the same as, or different from, the others of B, B.
sub.
1, and B.
sub.
2 ; and wherein each of a and b is independently 0 or 1.
The antitumor agent may be one of numerous chemotherapy agents such as an alkylating agent, an antimetabolite, a hormonal agent, an antibiotic, colchicine, a vinca alkaloid, L-asparaginase, procarbazine, hydroxyurea, mitotane, nitrosoureas or an imidazole carboxamide