Organosilicon Compounds, SILA-409 and SILA-421, as Doxorubicin Resistance-Reversing Agents in Human Colon Cancer Cells

Abstract

Multidrug resistance (MDR) that occurs in cancer cells constitutes one of the major reasons for chemotherapy failure. The main molecular mechanism of MDR is overexpression of protein transporters from the ATP-binding cassette (ABC) superfamily, such as ABCB1 (multidrug resistance protein 1 (MDR1), P-glycoprotein). At the expense of ATP hydrolysis, ABCB1 pumps a diverse range of substrates (including anticancer drugs) out of the cell, thereby reducing their intracellular concentration. In the present study, the ability of two patented disiloxanes (SILA-409 and SILA-421) to reverse drug resistance in human colon adenocarcinoma cell lines LoVo and LoVo/Dx was investigated. It was demonstrated that both compounds in concentrations of 0.5–1 µM strongly increased the sensitivity of LoVo/Dx cells to doxorubicin. By means of an accumulation test in which rhodamine 123 was used as an ABCB1 substrate analogue, both organosilicon compounds were also shown to inhibit ABCB1 transport activity. The intracellular accumulation of doxorubicin was also increased, and more drug entered the cellular nuclei of resistant cells in the presence of the studied compounds. In conclusion, both SILA-409 and SILA-421 were demonstrated to be effective MDR reversal agents in resistant human colon cancer cells.

TMPE Derived from Saffron Natural Monoterpene as Cytotoxic and Multidrug Resistance Reversing Agent in Colon Cancer Cells

“…Intracellular doxorubicin accumulation was measured using a LS-5 spectrofluorimeter (Perkin-Elmer, Beaconsfield, UK) as described previously [ 50 ]. Excitation and emission wavelengths were 475 and 553 nm, respectively.…”

Silicon switch: Carbon–silicon Bioisosteric replacement as a strategy to modulate the selectivity, physicochemical, and drug‐like properties in anticancer pharmacophores

“…A number of other silicon‐containing molecules have been evaluated for their anticancer properties. Wesołowska and coworkers developed a series of water‐soluble disiloxanes, with SILA‐409 ( 52 ) and SILA‐421 ( 53 ) (Figure 11) displaying a strong potency as potential doxorubicin resistance‐reversing agents in human colon adenocarcinoma cell lines LoVo and LoVo/Dx (Wesolowska et al, 2020).…”

An edge-based statistical analysis of long non-coding RNA expression profiles reveals a negative association between Parkinson’s disease and colon cancer

“…Figure 3 presents the enriched KEGG pathways and GO terms, along with their corresponding FDRs. Of these pathways, many have been found to be associated with both PD and CC, such as MAPK signaling pathway [36,37], ATP binding pathway [38,39], and cAMP signaling pathway [40][41][42]. Therefore, the investigation of the hub genes harnessed more evidence to support the link between PD and CC.…”