The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention

Table 1 Compounds known to induce cyclin D1 degradation in mammalian cell lines.

Compound	Conc.	T286 dependent?^a	Cell line	Proteasome inhibitor
All-trans retinoic acid (RA)	4–10 μM	Yes	BEAS-2B, NT2/D1	Lactacystin, LLnL^b
Differentiation-inducing factor-1 and 3 (DIF-1 and DIF-3)	30 μM	Yes^c	SCC, HeLa	MG132
1-Methyl-4-phenylpyridinium ion (MPP⁺)	300 nM	Yes	MG63	MG132
hypothemycin	0.5 μg/Ml	N.D.	NIH3T3-DT	Lactacystin
O-methyl deoxybouvardin (RA-VII)	100 nM	N.D.	DLD-1	Lactacystin
GL331	10 μM	N.D.	CL1-5	N-CBZ-L-L-L-AL
Resveratrol	300 μM	N.D.	SW480	LLnL^b
Diferuloylmethane (curcumin)	25 μM	N.D.	LnCap, various breast cancer derived	Lactacystin
Lovastatin	10 μM		PC-3-M	LLnL^{b, d}
Aspirin	5 nmol/L	Yes^e	SW480, HT-29	MG132
Cycloheximide	50 μM	No	MCF-7	MG132
15-deoxy-Δ^12,14 prostaglandin J₂ (PGJ2)^f	5–20 μM	N.D.	MCF-7	MG132, PSII
Ciglitazone^f	30–40 μM	N.D.	MCF-7	MG132, PSII
Troglitazone^f	40 μM	No	MCF-7	MG132, lactacystin, epoxomicin
Δ2-TG^g	5 μM	No	MCF-7	MG132, lactacystin, epoxomicin
Rapamycin	100 nmol/L	Yes	MCF-7, MDA-MB-468	LLnL^b
Trichostatin A (TSA)^h	1 μM	Yes/noⁱ	MCF-7, MDA-MB-231, KNRK	MG132, ALLN, lactacystin, NLVS^j
Sodium chloride (NaCl), calcium chloride (CaCl₂), magnesium chloride (MgCl₂)	50 mM	Yes^e	Granta 519	LLnL^b, lactacystin, MG132

a) T286 phosphorylation requirement, b) LLnL (ALLN, Calpain inhibitor 1, N-acetyl-leucyl-leucyl-norleucinal, MG101), c) Mirk/Dyrk 1b mediated T288 phosphorylation required, d) Lactacystin failed to abolish lovastatin induced cyclin D1 degradation, e) p38^SAPK2 mediated T286 phosphorylation, f) PGJ2, ciglitazone and troglitazone are PPARγ agonists, g) Δ2-TG is structurally related to troglitazone but lacks PPARγ agonist activity, h) TSA is a prototype HDAC inhibitor, i) partial requirement for GSK3β in TSA induced cyclin D1 degradation, j) NLVS (NIP-leu₃-vinyl sulphone)

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