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In an effort to identify novel anti-cancer agents, we employed a well-established High Throughput Screening (HTS) assay to assess the cytotoxic effect of compounds within the ChemBridge DIVERSet Library on a lymphoma cell line. This screen revealed a novel thiophene, F8 (methyl 5-[(dimethylamino)carbonyl]-4-methyl-2-[(3-phenyl-2-propynoyl) amino]-3-thiophenecarboxylate), that displays anti-cancer activity on lymphoma, leukemia, and other cancer cell lines. Thiophenes and thiophene derivatives have emerged as an important class of heterocyclic compounds that have displayed favorable drug characteristics. They have been previously reported to exhibit a broad spectrum of properties and varied uses in the field of medicine. In addition, they have proven to be effective drugs in various disease scenarios. They contain anti-inflammatory, anti-anxiety, anti-psychotic, anti-microbial, anti-fungal, estrogen receptor modulating, anti-mitotic, kinase inhibiting and anti-cancer activities, rendering compounds with a thiophene a subject of significant interest in the scientific community. Compound F8 consistently induced cell death at a low micromolar range on a small panel of cancer cell lines after a 48 h period. Further investigation revealed that F8 induced phosphatidylserine externalization, reactive oxygen species generation, mitochondrial depolarization, kinase inhibition, and induces apoptosis. These findings demonstrate that F8 has promising anti-cancer activity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Swain et al. 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.)

Reactive oxygen species are frequently associated with various cancers including pancreatic ductal adenocarcinomas (PDACs). Superoxide dismutase 2 (SOD2) is an enzyme that plays an important role in reactive oxygen species (ROS) signaling. Investigating the molecular function and biological functions of SOD2 can help us develop new therapeutic options and uncover new biomarkers for PDAC diagnosis and prognosis. Here, we show that nimbolide (NB), a triterpene limonoid, effectively blocks the growth and metastasis of PDACs by suppressing the expression and activity of SOD2. To identify the role of SOD2 in NB-induced anticancer activity, we used RNA interference to silence and plasmid transfection to overexpress it. Silencing SOD2 significantly reduced the growth and metastatic characteristics like epithelial-to-mesenchymal transition, invasion, migration, and colony-forming capabilities of PDACs, and NB treatment further reduced these characteristics. Conversely, the overexpression of SOD2 enhanced these metastatic characteristics. ROS signaling has a strong feedback mechanism with the PI3K/Akt signaling pathway, which could be mediated through SOD2. Finally, NB treatment to SOD2-overexpressing PDAC xenografts resulted in significant inhibition of tumor growth and metastasis. Overall, this work suggests that NB, a natural and safe phytochemical that silences SOD2 to induce high levels of ROS generation, results in increased apoptosis and reduced growth and progression of PDACs. The role of SOD2 in regulating NB-induced ROS generation presents itself as a therapeutic option for PDACs.

Cancer remains the second most common cause of death in the US. Due to a recurrent problem with anticancer drug resistance, there is a current need for anticancer drugs with distinct modes of action for combination drug therapy We have tested two novel piperidone compounds, named 2608 (1-dichloroacetyl - 3,5-bis(3,4-difluorobenzylidene)-4-piperidone) and 2610 (1-dichloroacetyl-3,5-bis(3,4-dichlorobenzylidene)-4-piperidone), for their potential cytotoxicity on numerous human cancer cell lines. We found that both compounds were cytotoxic for breast, pancreatic, leukemia, lymphoma, colon, and fibroblast cell lines, with a cytotoxic concentration 50% (CC 50 ) in the low micromolar to nanomolar concentration range. Further assays focused primarily on an acute lymphoblastic lymphoma and colon cancer cell lines since they were the most sensitive and resistant to the experimental piperidones. The cell death mechanism was evaluated through assays commonly used to detect the induction of apoptosis. These assays revealed that both 2608 and 2610 induced reactive oxygen species (ROS) accumulation, mitochondrial depolarization, and activated caspase-3/7. Our findings suggest that the piperidones induced cell death via the intrinsic apoptotic pathway. Additional assays revealed that both piperidones cause cell cycle alteration in lymphoma and colon cell lines. Both piperidones elicited DNA fragmentation, as evidenced by an increment in the sub-G0/G1 subpopulation in both cell lines. Similar to other related compounds, both piperidones were found to act as proteasome inhibitors by increasing the levels of poly-ubiquitinated proteins in both lymphoma and colon cell lines. Hence, the two piperidones exhibited attractive cytotoxic properties and suitable mechanisms of action, which makes them good candidates as anticancer drugs., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This study tested predictions from restraint theory [Herman & Polivy (1984). A boundary model for the regulation of eating. In: A. J. Stunkard, & E. Stellar (Eds.), Eating and its disorders (pp. 141-156) New York: Raven Press.] and the three-factor model of dieting [Psychol. Bull. 114 (1993) 100.] using an eating regulation paradigm. Participants were 42 obese, nonbinge eaters assigned to either a weight loss group (restrictive dieters or RDs) or a group designed to eliminate dieting ("undieters" or UDs). Participants took part in an ostensible ice cream taste test with or without a preload, both before and after the weight control intervention. At pretest, restraint theory's prediction that participants would engage in counter-regulatory eating was not supported. At posttest, after 8 weeks of the dieting interventions, RDs increased and UDs decreased their intake following a preload, a pattern most consistent with the predictions of restraint theory. This counter-regulatory trend was observed in spite of a significant decrease in RDs' Disinhibition scale scores following treatment. Implications of these findings for restraint theory, the three-factor model of dieting, and relapse in obesity treatment were discussed.

Background: Previous studies showed that resting energy expenditure (REE) is lower in obese African American women than in obese white women. It is unknown, however, whether there are racial differences in how REE responds to weight loss and energy restriction., Objective: We assessed REE, body composition, and respiratory quotient before and after weight loss in obese black and white women., Design: We measured REE by indirect calorimetry and body composition by densitometry before and after 20-24 wk of treatment with a 3870-4289-kJ/d diet. Subjects were 109 obese females (24 black, 85 white) with a mean (+/-SD) body mass index (in kg/m2) of 36.3+/-5.0, weight of 95.7+/-12.6 kg, and age of 42.3+/-8.1 y., Results: Before treatment, REE, adjusted for body composition, was significantly lower in black than in white subjects (P = 0.001). Black subjects lost significantly less weight during treatment than did white subjects (13.4+/-5.9 kg or 14.2+/-5.7% compared with 16.4+/-5.6 kg or 17.0+/-5.7%, respectively; P = 0.04). Analyses that controlled for initial REE and changes in fat mass and fat-free mass showed that blacks had significantly greater decreases in REE after treatment than did whites (9.9+/-7.3% compared with 6.3+/-7.4%; P = 0.02)., Conclusion: This study suggests that weight loss results in greater reductions in REE in obese black women than in obese white women. These data underscore the need to consider both biological and behavioral factors when setting expectations and assessing outcomes for obesity treatment in African American women.