Secondary Metabolites of Saussurea costus Leaf Extract Induce Apoptosis in Breast, Liver, and Colon Cancer Cells by Caspase-3-Dependent Intrinsic Pathway.

BACKGROUND: Apoptosis, a major form of programmed cell death, plays a vital role in regulating tissue development and maintenance of homeostasis in eukaryotes. Apoptosis can occur via a death receptor-dependent extrinsic or a mitochondrial-dependent intrinsic pathway and can be induced by various chemotherapeutic agents. In this study, the anticancer activity of Saussurea costus and its mode of intervention in human cancer cells of breast, colon, and liver were investigated. RESULTS: In this study, the bioactives of S. costus leaves were extensively extracted in five solvents of different polarity. The cytotoxicity and anticancer effect of the extracted secondary metabolites were investigated against breast (MCF-7), liver (HepG2), and colon (HCT116) cancer cell lines using a Sulphorhodamine B (SRB) assay. Secondary metabolites extracted using hexane, methanol, ethyl acetate, and chloroform had the highest cytotoxicity and thus the greatest anticancer effect on all the cancer cell lines tested (IC50; ranging from 0.25 to 2.5 µg/ml), while butanol was comparatively less active (IC50; ranging from 23.2 to 25.5 µg/ml). Further investigation using DNA flow cytometry and fluorescent microscopy revealed that the extract arrested the cells in the G1 phase of cell cycle and induced apoptosis. Furthermore, the elevated expression level of proapoptotic proteins and decreased expression level of antiapoptotic proteins confirmed that the intrinsic (mitochondrial) pathway was involved in mediating the apoptosis of cancer cells upon treatment with S. costus extract. These results altogether suggest that S. costus could be a potential anticancer agent. CONCLUSION: These results suggest that the S. costus extract is the potential source of the secondary metabolites that could be used as anticancer agent to treat diverse cancers of breast, colon, and liver.

Coexistence of diverse heavy metal pollution magnitudes: Health risk assessment of affected cattle and human population in some rural regions, Qena, Egypt.

OBJECTIVE: The purpose of this study was to measure the mean concentrations of heavy metals including aluminum (Al), arsenic, nickel (Ni), mercury, lead (Pb), and cadmium (Cd) and to assess the health hazards due to the exposure of cattle/human population to a distinct or the mixture of heavy metals through various sources. MATERIALS AND METHODS: A total of 180 samples including water sources, animal feed, and raw cows' milk from rural regions in Qena, Egypt, were examined using the inductively coupled plasma emission spectrometer (ICP; iCAP 6200). RESULTS: The data highlighted heavy metal pollution with variable concentrations among most of the investigated regions. All concentrations of Al, Ni, and Cd detected in the feeding stuff showed a strong correlation to their respective levels in milk rather than those detected in water (R 2= 0.072 vs. 0.039, 0.13 vs. 0.10, and 0.46 vs. 0.014, respectively) (p < 0.05). Anisocytosis and poikilocytosis with a tendency to rouleaux formation were evident, and basophilic stippling was a pathognomic indicator for heavy metal toxicity, especially Pb. Leukopenia and macrocytic anemia were shown in 50% and 65% of examined cattle, respectively. The target hazard quotients values were more than one (>1) for all heavy metals from water intake for both children and adults and Al and Cd in milk for children, and the hazard index values were indicated higher for noncarcinogenic health hazards. The target cancer risk values predispose people in the surveyed villages to higher cancerous risks due to exposures to the mixture of heavy metal through the consumption of water and milk. CONCLUSION: The bioaccumulation and transmission of heavy metal mixtures from water sources and feeding material have detrimental influences on milk pollution and cattle health which seem to be a serious issue affecting public health in those rural communities.