Lowering the apoptotic threshold in colorectal cancer cells by targeting mitochondria

This study showed dose-dependent cytotoxic effects of cisplatin, oxaliplatin and doxycycline in HT29 colorectal cancer cells. Doxycycline showed inhibition of cytochrome-c-oxidase activity in these cells over a time-period. The pre-treatment of doxycycline reported statistically significant increased cytotoxicity of cisplatin and oxaliplatin compared to cisplatin and oxaliplatin alone. The caspase studies revealed significantly less expression and activity of caspase 3 in HT29 cells pre-treated with doxycycline compared to the cells treated with cisplatin and oxaliplatin alone.It was concluded that doxycycline lowered the apoptotic threshold in HT 29 cells by targeting mitochondria. This also raised possible caspase-independent mechanisms of apoptosis in HT29 cells when pre-treated with doxycycline however this needs further research work.Tetracyclines (TCNs) have long been used widely in clinical practice as antibiotics in various bacterial, mycoplasma, chlamydiae, rickettsiae and protozoan infections. Their main mechanism of action involves inhibition of protein synthesis by restricting binding of aminoacyl t-RNA to 30 S ribosomes. TCNs are believed to interfere in mitochondrial protein synthesis that let to the discovery of other effects of TCNs independent of their antimicrobial actions[1]. Recently, a renewed interest in study of TCNs has evolved due to their ability to inhibit matrix metalloproteinases (MMPs) in various cancers such as prostate[2], melanoma[3], osteosarcoma[4], breast[5], leukaemia [6] and colorectal cancers[7]. Some of TCNs have been shown to work as apoptotic inducers[8]. Despite TCNs' emerging role as anti-invasive and anti-proliferative drugs in cancer treatment, their apoptotic mechanisms are yet to be precisely defined.Apoptosis is the mechanism by which chemotherapeutic agents induce cancer cell death[9]. There are two main mechanisms of apotptosis; the intrinsic and extrinsic pathways. Caspases, the proteolyic enzymes, cysteine proteas