A Novel Carbazole Derivative, BMVC: a Potential Antitumor Agent and Fluorescence Marker of Cancer Cells

Abstract

We have investigated a novel compound, 3,6-bis[2-(1-methylpyridinium)vinyl]carbazole diiodide (BMVC), for inhibiting telomerase activity and distinguishing human lung H1299 and oral Ca9-22 cancer cells from lung IMR90 and skin Detroit-551 normal fibroblast cells. The telomeric repeat amplification protocol (TRAP) assay shows that the concentration of BMVC that inhibits 50% of the telomerase activity (IC50) is ca. 0.05 microM. On the other hand, the cell-viability assay indicates that the cytotoxicity was less than 15% to the H1299 and Ca9-22 cancer cells, and almost negligible to the MRC-5 and Detroit-551 normal cells after incubation with 0.5 microM BMVC for 72 h. The low concentration of 0.05 microM of BMVC can inhibit telomerase activity but does not have general toxic effects to normal cells, implying that BMVC is a promising telomerase inhibitor. Moreover, wide-field fluorescence images of 0.1 microM BMVC-treated cells show bright fluorescence spots in the nuclei of the most H1299 and Ca9-22 cancer cells. Interestingly, similar fluorescence spots are hardly observed in the nuclei of the IMR90 and Detroit-551 normal cells, implying that BMVC might be a useful marker to distinguish tumor cells and normal cells.

G-Quadruplex Stabilizer 3,6-Bis(1-Methyl-4-Vinylpyridinium)Carbazole Diiodide Induces Accelerated Senescence and Inhibits Tumorigenic Properties in Cancer Cells

“…We have previously identified a carbazole derivative, BMVC, as a potent G-quadruplex stabilizer and telomerase inhibitor (25,26). BMVC has cationic charge on the two pendant groups of pyridinium rings of carbazole (Fig.…”

Telomere and telomerase as targets for anti-cancer and regeneration therapies

“…Moreover, cancer cells pretreated with BIBR1532 showed a reduced tumorigenic potential in the mouse xenograft model [26] . With the IC 50 value at nanomolar concentration, BIBR1532 and several other compounds should have the potential for further developments [26][27][28] . Targeting telomeres In humans, the G-rich telomeric DNA tails are capable of forming a planar structure, termed G-quadruplexes, through non-Watson-Crick Hoogsteen hydrogen bonding in vitro [29] .…”

“…Successful lead compounds that were identified include derivatives of proflavins [28] , porphyrins [34] , acridines [35] , anthraquinones [36] , triazines [37] , and carbazoles [27] . All of these identified compounds have planar aromatic rings.…”

“…For example, a carbazole derivative BMVC increases the melting temperature (Tm) of Gquadruplexes formed by human telomeric DNA by as much as 13 ºC [40] . It is interesting to note that these planar compounds appear to be very effective in affecting telomerase as several of these compounds have the IC 50 at the range of nanomolar concentration [27,28,37] .…”

A Dual Selective Antitumor Agent and Fluorescence Probe: the Binary BMVC–Porphyrin Photosensitizer

“…We recently synthesized a novel 3,6-bis-(1-methyl-4-vinylpyridinium)-carbazole diiodide (BMVC) compound with selectivity toward cancer cells over normal cells. [12,13] Specifically, the fluorescence of BMVC detected in cancer cells was found to be much stronger than that in normal cells. [14] Moreover, BMVC has a large cross-section for two-photon absorption around 820 nm, [15] a wavelength that is close to optimal for tissue penetration of the radiation needed to excite the photosensitizer.…”