2 research outputs found
Additional file 1: of Estrogenic and cytotoxic potentials of compounds isolated from Millettia macrophylla Benth (Fabaceae): towards a better understanding of its underlying mechanisms
Figure S1. 1H NMR (600 MHz, CD3OD) spectrum of compound 6. Figure S2. ESI-MS (negative mode ionization) spectrum of compound 6. Figure S3. 1H NMR (600 MHz, CD3OD) spectrum of compound 13. Figure S4. ESI-MS (positive mode ionization) spectrum of compound 13. (DOC 112 kb
Antitumoral Activity of a Trichloromethyl Pyrimidine Analogue: Molecular Cross-Talk between Intrinsic and Extrinsic Apoptosis
Acute
lymphoblastic leukemia (ALL) is a malignant disorder caused
by the proliferation of lymphoid progenitor cells and is the most
common cancer in children. Cytotoxic nucleoside analogues are important
chemotherapeutic agents, which are used in many cancers, including
leukemias. In this study, we investigated the effects of the synthetic
nucleoside analogue 1-(5,5,5-trichloro-2-methoxy-4-oxopenten-2-yl)-4-trichloromethyl-pyrimidin-2(1<i>H</i>)-one, named compound 3 or <b>C3</b>, on leukemia
cell lines. The compound stimulated cell death by apoptosis, evidenced
by DNA fragmentation, phosphatidylserine externalization, and caspase-3
activation. Compound 3 seemed to trigger several cell death pathways.
The mitochondrial pathway was evidenced through a disturbance of mitochondrial
membrane potential, strong cytochrome <i>c</i> liberation,
decrease of antiapoptotic Bcl-2 protein expression, and caspase-9
activation. The <b>C3</b> also induced caspase-8 and -12 activation,
an increase in the intracellular calcium level, and an overproduction
of reactive oxygen species. Increased caspase 8 activity suggests
that the extrinsic pathway was activated and that the ROS production
and enzyme activity alteration (glutathione <i>S</i>-transferase,
glutathione peroxidase, catalase, and glutathione reductase) might
be related to oxidative stress. Finally, the increase in calcium release,
CHOP expression, and caspase-12 activity might characterize endoplasmic
reticulum stress. Compound 3 was likewise cytotoxic to leukemic and
melanoma human cell lines. Taken together, the results contribute
to further understanding the new pyrimidine analogue as a potential
chemotherapeutic drug or lead molecule