10H-3,6-Diazaphenothiazines triggered the mitochondrial-dependent and cell death receptor-dependent apoptosis pathways and further increased the chemosensitivity of MCF-7 breast cancer cells via inhibition of AKT1 pathways.

Breast cancer is one of the leading causes of death in cancer categories, followed by lung, colorectal, and ovarian among the female gender across the world. 10H-3,6-diazaphenothiazine (PTZ) is a thiazine derivative compound that exhibits many pharmacological activities. Herein, we proceed to investigate the pharmacological activities of PTZ toward breast cancer MCF-7 cells as a representative in vitro breast cancer cell model. The PTZ exhibited a proliferation inhibition (IC50 = 0.895 µM) toward MCF-7 cells. Further, cell cycle analysis illustrated that the S-phase checkpoint was activated to achieve proliferation inhibition. In vitro cytotoxicity test on three normal cell lines (HEK293 normal kidney cells, MCF-10A normal breast cells, and H9C2 normal heart cells) demonstrated that PTZ was more potent toward cancer cells. Increase in the levels of reactive oxygen species results in polarization of mitochondrial membrane potential (ΔΨm), together with suppression of mitochondrial thioredoxin reductase enzymatic activity suggested that PTZ induced oxidative damages toward mitochondria and contributed to improved drug efficacy toward treatment. The RT2 PCR Profiler Array (human apoptosis pathways) proved that PTZ induced cell death via mitochondria-dependent and cell death receptor-dependent pathways, through a series of modulation of caspases, and the respective morphology of apoptosis was observed. Mechanistic studies of apoptosis suggested that PTZ inhibited AKT1 pathways resulting in enhanced drug efficacy despite it preventing invasion of cancer cells. These results showed the effectiveness of PTZ in initiation of apoptosis, programmed cell death, toward highly chemoresistant MCF-7 cells, thus suggesting its potential as a chemotherapeutic drug.

The dilemma of diagnosing wound botulism in an infant: A rare case of paralysis with topical application of honey.

Botulism is a form of paralysis caused by a neurotoxin produced by the bacterium Clostridium botulinum. It is well known that natural honey contains Clostridium botulinum spores; controversy arises when a honey-related product is being used for wound care, where the possibility occurs of applying these spores to an open wound. To our knowledge, no reported cases of medical-grade honey have been associated with wound botulism. Given this fact, do we feel secure regarding the safety of this product, and will it be enough to alleviate our concern? We present a case of an infant with an infected umbilical stump, which required a surgical wound debridement. This infant developed a sudden progressive flaccid paralysis a few days after the application of topical medical grade honey for wound care. Even though suspicion of wound botulism is high, confirmation of the diagnosis, detection of neurotoxin, and isolating the organism remains a challenge.