Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT

Mechanism of Action of Two Flavone Isomers Targeting Cancer Cells with Varying Cell Differentiation Status

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Apoptosis can be triggered in two different ways, through the intrinsic or the extrinsic pathway. The intrinsic pathway is mediated by the mitochondria via the release of cytochrome C while the extrinsic pathway is prompted by death receptor signals and bypasses the mitochondria. These two pathways are closely related to cell proliferation and survival signaling cascades, which thereby constitute possible targets for cancer therapy. In previous studies we introduced two plant derived isomeric flavonoids, flavone A and flavone B which induce apoptosis in highly tumorigenic cancer cells of the breast, colon, pancreas, and the prostate. Flavone A displayed potent cytotoxic activity against more differentiated carcinomas of the colon (CaCo-2) and the pancreas (Panc28), whereas flavone B cytotoxic action is observed on poorly differentiated carcinomas of the colon (HCT 116) and pancreas (MIA PaCa). Apoptosis is induced by flavone A in better differentiated colon cancer CaCo-2 and pancreatic cancer Panc 28 cells via the intrinsic pathway by the inhibition of the activated forms of extracellular signal-regulated kinase (ERK) and pS6, and subsequent loss of phosphorylation of Bcl-2 associated death promoter (BAD) protein, while apoptosis is triggered by flavone B in poorly differentiated colon cancer HCT 116 and MIA PaCa pancreatic cancer cells through the extrinsic pathway with the concomitant upregulation of the phosphorylated forms of ERK and c-JUN at serine 73. These changes in protein levels ultimately lead to activation of apoptosis, without the involvement of AKT

The Youngest Victims of Violence: Examining the Mental Health Needs of Young Children Who Are Involved in the Child Welfare and Juvenile Justice Systems

Children placed in the state\u27s custody due to neglect, abuse or maltreatment are one of America\u27s most vulnerable populations. Seventy-five percent of child victims of maltreatment are under the age of 12. Not only is their suffering a problem, these children are also at increased risk for delinquent behavior later in life. While research has documented the potential long-term consequences of child abuse and neglect, the mental health needs of young children involved in the foster care and juvenile justice systems have been largely overlooked. This study examined the social, emotional and behavioral difficulties of 670 children, age 3-11, who were involved in the child welfare and juvenile justice systems. Children in this study were living in residential treatment facilities, group homes, foster care homes or were receiving intensive home-based services. To assess the children\u27s mental health needs caregivers completed the parent form of the Strengths and Difficulties Questionnaire (Goodman, Journal of Child Psychology and Psychiatry 38:581-586, 1997). The findings indicated a high prevalence of mental health problems, with 81 % of the children in the sample having a total difficulties score in the borderline or abnormal range and 90 % of the children having borderline or abnormal scores on at least one of the subscales (conduct, emotional, peer or attention problems). When characteristics such as gender, race and age were considered significant differences were found among boys and girls, Caucasian and minority children, and age groups. The findings highlight the importance of mental health assessment and interventions that are gender and culturally sensitive and developmentally appropriate. © 2012 Springer Science+Business Media New York

Child Welfare and Juvenile Justice: Examining the Unique Mental Health Needs of Girls

This study investigated the prevalence of mental health problems among girls who are involved in child welfare or juvenile justice systems. The sample consisted of 1,193 girls ranging in age from 4 to 18, the majority (82.3%, n = 982) of which were older than age 12. Differences based on race/ethnicity and developmental age groups were examined. Consistent with other research, this study found that the mental health needs of girls involved in the child welfare or juvenile justice systems are several times higher than in the general population. Intervention approaches must be developed that take into consideration differences in gender, age, and racial and ethnic group. © 2013 Copyright Taylor and Francis Group, LLC

Increased cytotoxicity of 3,5 dihydroxy -7- methoxyflavone in MIA PaCa-2 and Panc28 pancreatic cancer cells when used in conjunction with proliferative compound 3,5 dihydroxy-7-methoxyflavanone both derived from Chromolaena leivensis (Hieron)

Over 5000 flavonoids have been identified so far and many of these are known to have antineoplastic properties. The relationships between the targeting activities by these compounds on cancer cells and the specific features that determine their molecular structures are not completely elucidated. Here we report the differential cytotoxic effects of two unsubstituted ring B flavonoids that differ solely in the presence of a C2, C3 double bond in ring C, on human cancer cells of the lung (A549), pancreas (MIA PaCa-2, Panc28), colon (HCT 116, CaCo-2), Liver (HepG2), and breast (SKBr3). These compounds were extracted from Chromolaena leivensis (Hieron) a plant belonging to the genus Chromolaena reputed to have antitumor activities. 3, 5 dihydroxy-7-methoxyflavone induce apoptosis in cancer cells of the lung A549, pancreas MIA PaCa-2 and Panc28, and colon HCT116, but not on Caco-2; whereas 3,5 dihydroxy-7-methoxyflavanone display proliferative effects in A549, Panc 28, MIA PaCa, and HCT116 cells at low concentrations, and slight cytotoxicity only on CaCo-2, a cancer cell line with a higher differentiation status than other cells tested. At the concentrations studied (5-80µM) neither compound demonstrated activity against cancer cells of the liver (HepG2) or breast (SKBr3) as indicated by MTT cell viability assays. When used in combination with 3,5 dihydroxy-7-methoxyflavone in pancreatic cancer cells, the targeting preference of 3, 5 dihydroxy-7-methoxyflavanone is altered, and a significant increase in inhibition of cell viability is observed 48 hours after dosing. The presence or absence of the C2, C3 double bond in ring C, accounts for electrochemical and structural changes that dictate differential specificity towards cancer cells. 3,5 dihydroxy-7-methoxyflavone has a more planar structure, whereas the absence of the double bond in C2, C3 causes ring B to adopt a perpendicular orientation to the plane formed by rings A and C and the OH group at C3

Increased Cytotoxicity of 3,5 Dihydroxy -7- Methoxyflavone in MIA PaCa-2 and Panc28 Pancreatic Cancer Cells When Used in Conjunction With Proliferative Compound 3,5 Dihydroxy-7-Methoxyflavanone Both Derived From Chromolaena Leivensis (Hieron)

Over 5000 flavonoids have been identified so far and many of these are known to have antineoplastic properties. The relationships between the targeting activities by these compounds on cancer cells and the specific features that determine their molecular structures are not completely elucidated. Here we report the differential cytotoxic effects of two unsubstituted ring B flavonoids that differ solely in the presence of a C2, C3 double bond in ring C, on human cancer cells of the lung (A549), pancreas (MIA PaCa-2, Panc28), colon (HCT 116, CaCo-2), Liver (HepG2), and breast (SKBr3). These compounds were extracted from Chromolaena leivensis (Hieron) a plant belonging to the genus Chromolaena reputed to have antitumor activities. 3, 5 dihydroxy-7-methoxyflavone induce apoptosis in cancer cells of the lung A549, pancreas MIA PaCa-2 and Panc28, and colon HCT116, but not on Caco-2; whereas 3,5 dihydroxy-7-methoxyflavanone display proliferative effects in A549, Panc 28, MIA PaCa, and HCT116 cells at low concentrations, and slight cytotoxicity only on CaCo-2, a cancer cell line with a higher differentiation status than other cells tested. At the concentrations studied (5-80µM) neither compound demonstrated activity against cancer cells of the liver (HepG2) or breast (SKBr3) as indicated by MTT cell viability assays. When used in combination with 3,5 dihydroxy-7-methoxyflavone in pancreatic cancer cells, the targeting preference of 3, 5 dihydroxy-7-methoxyflavanone is altered, and a significant increase in inhibition of cell viability is observed 48 hours after dosing. The presence or absence of the C2, C3 double bond in ring C, accounts for electrochemical and structural changes that dictate differential specificity towards cancer cells. 3,5 dihydroxy-7-methoxyflavone has a more planar structure, whereas the absence of the double bond in C2, C3 causes ring B to adopt a perpendicular orientation to the plane formed by rings A and C and the OH group at C3