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Ethnopharmacological Relevance: Hypericum roeperianum is a medicinal spice traditionally used in West Africa to treat female sterility, fungal infections, and cancer. It has previously been reported that H. roeperianum exhibits cytotoxic potential by reducing the viability of cancer cells involving multidrug-resistant phenotypes, but its underlying molecular mechanism remains unknown., Aim of the Study: The mechanistic involvement of H. roeperianum methanolic crude extract (HRC) in attenuating breast cancer progression by exploring the effects on mitochondrial apoptosis and epithelial-mesenchymal transition (EMT) was investigated., Materials and Methods: In the present study, we examined the anticancer properties of HRC through MTT assay, colony formation, wound healing assay, spheroid formation, DNA fragmentation and flow cytometry for cell cycle arrest, apoptosis (Annexin V/PI staining) and mitochondrial membrane potential (MMP) (JC-1) detection. In addition, western blot analysis of various proteins and quantitative real time PCR of various genes involved in apoptosis, EMT and the PI3K/Akt/mToR signal transduction pathway were performed., Results: This study revealed that HRC treatment significantly decreased breast cancer cell viability, colony forming efficiency and reduced the ability of cell migration and spheroid formation. HRC also induced apoptosis in MDA-MB-231 and MCF-7 via promoting G0/G1 cell cycle arrest, disruption of mitochondrial membrane potential and induction of DNA damage. The crude extract induced apoptosis by activating the intrinsic pathway with a stronger effect that relies on the combined potency of associated molecular markers including Bax, Bad, Bcl-2, cytochrome C, caspase-9, and cleaved-PARP. It was also found that HRC regulates the PI3K/Akt/mToR pathway. In addition, HRC inhibited EMT by expressional alteration of Vimentin and E-cadherin, as well as the regulatory transcription factors such as Snail and Slug. The in vitro findings reflected similar mechanistic approach in 4T1 cell induced syngeneic mice model, indicating the reduction of tumor volume along with the significant expressional alteration of EMT and apoptotic markers., Conclusion: Taken together the findings concluded that H. roeperianum is a potential source of cytotoxic phytochemicals that exhibit abortifacient effect on breast cancer, both in vitro and in vivo, thus could further be utilized in breast cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

o‐Aminoazotoluene (OAT), capable of photoisomerization, and o‐vanillin, a potent comutagen, have been used to synthesize a new ligand, HL, [C6H4(CH3)N=NC6H3(CH3)N=CHC6H3(OH)(OCH3)], which, upon complexation with copper(II), results in a new copper(II) complex‐Cu(L)2, [Cu{C6H4(CH3)N=NC6H3(CH3)N=CHC6H3(OCH3)O}2]. Both HL and Cu(L)2 have been characterized by single‐crystal X‐ray diffraction measurements along with other analytical techniques, for example, IR spectroscopy, NMR spectroscopy, UV–Vis spectroscopy, elemental analysis and mass spectrometry. These compounds were tested with different in vitro anticancer assay as well as with in silico studies. A comparative study has been demonstrated on anticancer activity of HL and Cu(L)2 with the ligand HAZ, {C6H5N=NC6H4N=CHC6H3(OH)(OCH3)} and its Cu‐complex, [Cu(AZ)2, Cu{C6H5N=NC6H4N=CHC6H3(OCH3)O}2]. The sensing properties of HAZ, along with the synthesis and structural properties of both HAZ and Cu(AZ)2, have been reported by our group earlier. Cytotoxicity measurements on MCF7 cell lines show that Cu(L)2 and Cu(AZ)2 have higher anticancer activity than their corresponding ligands. The apoptotic effect of Cu‐complex was studied through nuclear fragmentation assay and AO/EB dual‐staining assay on MCF7 cell line. The IC50 value of Cu(L)2 in 0.01% DMSO/water after 24‐h treatment was found 4.2 μM, which is one of the lowest values with this response time compared to the other analogous anticancer compounds. Finally, we have evaluated the expression of hERα protein with respect to Cu‐complexes, and it was observed that Cu(L)2 caused more down‐regulation of hERα as compared to Cu(AZ)2. [ABSTRACT FROM AUTHOR]

Basis: Our learning from the limited trajectory of biomarker guided and genomic assay based response prediction to inform clinical action ability of cancers led to the strategic rethinking of developing and validating robust and individualized platform (CANScript) that make prediction based on multiple phenotypic inputs. Methods: Accelerated CANScript Enabled Personalized Treatment (ACCEPT) is an investigator initiated study aiming to predict response to anticancer drugs at clinic. Surgically resected tumors from primary breast cancer patients (n=30) were cultured in slices and treated with Epirubicin, Cyclophosphamide and 5FU in CANScript platform for three days in presence of autologous growth factors, immune milieu and indication specific matrix support where patient tumor microenvironment was extensively preserved. The outcome was measured by integrating both pathological (tumor content, viability, proliferation and induction of apoptosis) and kinetic endpoints (cell viability and metabolism) into a single data trained M score algorithm as described (Majumder B et al., Nature Commun, 2015, Brijwani N et al., Scientific Reports, 2017). After 6 cycles of therapy, following surgery, patients were clinically evaluated for response based on multiple criteria including radiological examination. This short-term clinical response was compared with CANScript driven response prediction. Results: Out of 25 evaluable patients, outcome is available for ten patients (40%) till today. Data indicate that CANScript derived predictive scores for responders and non-responders were highly correlated with clinical observation. For all six clinical non-responders, CANScript guided outcome was found to be matched with clinical outcome. Similarly, for rest 4 patients, while CANScript predicted response, 3 patients showed clinical response. These preliminary data from an ongoing study are encouraging and more patients will be enrolled and follow up data will be collected. Conclusion: Phenotypic assay based platform technologies are emerging as a new frontier of individual response prediction based on the complex and dynamic interplay of tumor and stroma including immune network. CANScript guided prediction of response showed encouraging results to understand the response of drugs at clinic, would offer further opportunity to incorporate phenotypic inputs for informed treatment decision in an adjuvant setting. [ABSTRACT FROM AUTHOR]

Basis: Our learning from the limited trajectory of biomarker guided and genomic assay based response prediction to inform clinical action ability of cancers led to the strategic rethinking of developing and validating robust and individualized platform (CANScript) that make prediction based on multiple phenotypic inputs. Methods: Accelerated CANScript Enabled Personalized Treatment (ACCEPT) is an investigator initiated study aiming to predict response to anticancer drugs at clinic. Surgically resected tumors from primary breast cancer patients (n=30) were cultured in slices and treated with Epirubicin, Cyclophosphamide and 5FU in CANScript platform for three days in presence of autologous growth factors, immune milieu and indication specific matrix support where patient tumor microenvironment was extensively preserved. The outcome was measured by integrating both pathological (tumor content, viability, proliferation and induction of apoptosis) and kinetic endpoints (cell viability and metabolism) into a single data trained M score algorithm as described (Majumder B et al., Nature Commun, 2015, Brijwani N et al., Scientific Reports, 2017). After 6 cycles of therapy, following surgery, patients were clinically evaluated for response based on multiple criteria including radiological examination. This short-term clinical response was compared with CANScript driven response prediction. Results: Out of 25 evaluable patients, outcome is available for ten patients (40%) till today. Data indicate that CANScript derived predictive scores for responders and non-responders were highly correlated with clinical observation. For all six clinical non-responders, CANScript guided outcome was found to be matched with clinical outcome. Similarly, for rest 4 patients, while CANScript predicted response, 3 patients showed clinical response. These preliminary data from an ongoing study are encouraging and more patients will be enrolled and follow up data will be collected. Conclusion: Phenotypic assay based platform technologies are emerging as a new frontier of individual response prediction based on the complex and dynamic interplay of tumor and stroma including immune network. CANScript guided prediction of response showed encouraging results to understand the response of drugs at clinic, would offer further opportunity to incorporate phenotypic inputs for informed treatment decision in an adjuvant setting. [ABSTRACT FROM AUTHOR]