DNA damage, lysosomal degradation and Bcl-xL deamidation in doxycycline- and minocycline-induced cell death in the K562 leukemic cell line

Abstract

We investigated mechanisms of cytotoxicity induced by doxycycline (doxy) and minocycline (mino) in the chronic myeloid leukemia K562 cell line. Doxy and mino induced cell death in exposure-dependent manner. While annexin V/propidium iodide staining was consistent with apoptosis, the morphological changes in Giemsa staining were more equivocal. A pancaspase inhibitor Z-VAD-FMK partially reverted cell death morphology, but concurrently completely prevented PARP cleavage. Mitochondrial involvement was detected as dissipation of mitochondrial membrane potential and cytochrome C release. DNA double strand breaks detected with γH2AX antibody and caspase-2 activation were found early after the treatment start, but caspase-3 activation was a late event. Decrement of Bcl-xL protein levels and electrophoretic shift of Bcl-xL molecule were induced by both drugs. Phosphorylation of Bcl-xL at serine 62 was ruled out. Similarly, Bcr/Abl tyrosine kinase levels were decreased. Lysosomal inhibitor chloroquine restored Bcl-xL and Bcr/Abl protein levels and inhibited caspase-3 activation. Thus, the cytotoxicity of doxy and mino in K562 cells is mediated by DNA damage, Bcl-xL deamidation and lysosomal degradation with activation of mitochondrial pathway of apoptosis.

Fabrication, Characterization and Response Surface Method (RSM) Optimization for Tetracycline Photodegration by Bi3.84W0.16O6.24- graphene oxide (BWO-GO)

“…Traditionally, it was not regarded as environmental pollutants; however, its occurrence in aquatic systems has attracted more and more attention as biological impacts and potential risks to the environment, as well as to human health, have been reported1234. Recently, photocatalytic TC degradation has attracted more and more concentration, as the photocatalysis technology is economic, environmental and nontoxic and owns considerable application.…”

“…Many Bi 3+ - and Bi 5+ -containing compounds have been found to possess a narrow band gap and exhibit visible light photocatalytic activity because of the hybridized O2p and Bi6s2 valence bands9101112, such as Bi 2 MoO 6 13, BiOI14, Bi 2 WO 6 15, Bi 2 O 2 CO 3 16. However, all these Bi-based photocatalysts don’t show great photocatalytic performance.…”

Modified‐release oral pellets for duodenum delivery of doxycycline hyclate

“…DOXY was chemically active with three pKa values (c.a., 3, 8, and 9) (Fares, Abedi‐Valugerdi, Hassan, & Potacova, ; Hoseini & Bagheri Gh, ). The chemical instability of DOXY was a concern that must be addressed (Borghi et al, ; Rasimick et al, ; Suarez et al, ).…”

Doxycycline directly targets PAR1 to suppress tumor progression

“…Endothelial cells originate from the mesoderm and have a similar origin and similar biomarkers to those of melanoma, sarcoma, neurogenic tumors (oat cell cancer) and triple-negative breast cancer [29]. Doxycycline was found to inhibit cell progression and tumor growth of cells with high PAR1 expression both in vitro and in vivo .…”