Background/Aims: Mitoxanthrone (MX) is an anthracenedione antineoplastic agent. Whether this drug and other related compounds have any effects on ion currents in osteoclasts remains largely unclear. Methods: In this study, the effects of MX and other related compounds on inwardly rectifying K⁺ current (I_K(IR)) were investigated in RAW 264.7 osteoclast precursor cells treated with lipopolysaccharide. Results: The I_K(IR) in these cells are blocked by BaCl₂ (1 mM). MX (1-100 µM) decreased the amplitude of I_K(IR) in a concentration-dependent manner with an IC₅₀ value of 6.4 µM. MX also slowed the time course of I_K(IR) inactivation elicited by large hyperpolarization. Doxorubicin (10 µM), 17β-estradiol (10 µM) and tertiapin (1 µM) decreased the I_K(IR) amplitude in these cells. In bafilomycin A₁-treated cells, MX-mediated block of I_K(IR) still existed. In cell-attached configuration, when the electrode was filled with MX (10 µM), the activity of inwardly rectifying K⁺ (Kir) channels was decreased with no change in single-channel conductance. MX-mediated reduction of channel activity is accompanied by a shortening of mean open time. Under current-clamp conditions, addition of MX resulted in membrane depolarization. Therefore, MX can interact with the Kir channels to decrease amplitude and to depolarize the membrane in these cells. Conclusion: The block by ^{the I}K(IR)this drug of Kir2.1 channels appears to be one of the important mechanisms underlying its actions on the resorptive activity of osteoclasts, if similar results occur in vivo. Targeting at Kir channels may be clinically useful as an adjunctive regimen to anti-cancer drugs (e.g., MX or doxorubicin) in influencing the resorptive activity of osteoclasts.

The androgen receptor (AR) poly‐glutamine polymorphism (AR‐Q) was reported to play role in endometrial cancer (EMCA) development, yet controversial. Environmental factors interact with genetic variation have been reported in EMCA. Aerosol toxins, polycyclic aromatic hydrocarbon benzo[a]pyrene (BaP), are EMCA facilitators. This report examined the interplay between AR‐Qs and BaP in EMCA. During analysing patient AR‐Q polymorphism and Aryl hydrocarbon Receptor (AhR) expressions, we found overall survival (OS) benefit is ascending with AR‐Q lengths (5‐year OS of 61.3% in Q length <20 and 88% in Q length >23). And AhR is higher expressed in short AR‐Q tumour compared to that in long AR‐Q patient. In vitro study found androgen‐response element (ARE) activity descends with AR‐Qs length (Q13 > Q25 > Q35), whereas BaP suppresses ARE activities in EMCA cells. Furthermore, AR‐Q13 (but not AR‐Q25, or ‐35) enhances BaP‐induced dioxin‐responsive element (DRE) activity. Lastly, AR‐Q13 exerts higher colony‐forming capacity than other AR‐Qs, and knock‐down AhR abolished AR‐Q13‐mediated colony numbers. This study demonstrated a possible interaction of gene (AR‐Q polymorphism) and environmental toxins (e.g. BaP) to affect cancer progression. A large‐scale epidemiology and public health survey on the interaction of environmental toxin and AR poly‐Q in EMCA is suggested.

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