Cervical cancer is the second most common cancer in women worldwide. Human papillomavirus (HPV) infection appears to be a necessary factor in the development of almost all cases (>95%) of cervical cancer. HPV E6 induces a change of control of p53 stabilization from Hdm2 to E6/E6AP in HPV-infected cells. It is well known that the LxxLL motif of cellular ubiquitin ligase E6AP binds to the pocket of E6 and causes a conformational change to enable E6 to bind p53 competently. In the ternary complex E6/E6AP/p53, p53 is polyubiquitinated by E6AP and subsequently degraded by a proteasome. Therefore, these cells are deficient in the processes regulated by p53, including apoptosis, damaged DNA repair, and the cell cycle. In the present study, it was demonstrated that quercetin induced G2 phase cell cycle arrest and apoptosis in both HeLa and SiHa cells, accompanied by an increase of p53 and its nuclear signal. It was also observed that quercetin increased the level of the p21 transcript and the pro-apoptotic Bax protein, which are two p53-downstream effectors. However, quercetin did not alter the expression of the HPV E6 protein in cervical cancer cells; therefore, the increase in p53 occurred in an E6 expression-independent manner. Furthermore, molecular docking demonstrated that quercetin binds stably in the central pocket of E6, the binding site of E6AP. These data suggest that quercetin increases the nuclear localization of p53 by interrupting E6/E6AP complex formation in cervical cancer cells.

Paclitaxel (PTX) is currently used as a front-line chemotherapeutic agent for several types of cancer, including ovarian carcinoma; however, PTX-resistance frequently arises through multiple mechanisms. The development of new strategies using natural compounds and PTX in combination has been the aim of several prior studies, in order to enhance the efficacy of chemotherapy. In this study, we found the following: (i) gallic acid (GA), a phenolic compound, potentiated the capacity of PTX to decrease proliferation and to cause G2/M cycle arrest in the PTX-resistant A2780AD ovarian cancer cell line; (ii) GA exerted a pro-oxidant action by increasing the production of reactive oxygen species (ROS), and co-treatment with the antioxidant agent N‑acetyl-L‑cysteine (NAC) prevented GA+PTX-induced cell proliferation inhibition and G2/M phase arrest; (iii) PTX stimulated ERK phosphorylation/activation, and co-treatment with the MEK/ERK inhibitor PD98049 potentiated the proliferation inhibition and G2/M phase arrest; (iv) and finally, GA abrogated the PTX-induced stimulation of ERK phosphorylation, a response that was prevented by co-treatment with NAC. Taken together, these results indicate that GA sensitizes PTX-resistant ovarian carcinoma cells via the ROS‑mediated inactivation of ERK, and suggest that GA could represent a useful co-adjuvant to PTX in ovarian carcinoma treatment.

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Caesalpinia coriaria (C. coriaria), also named cascalote, has been known traditionally in México for having cicatrizing and inflammatory properties. Phytochemical reports on Caesalpinia species have identified a high content of phenolic compounds and shown antineoplastic effects against cancer cells. The aim of this study was to isolate and identify the active compounds of a water:acetone:ethanol (WAE) extract of C. coriaria pods and characterize their cytotoxic effect and cell death induction in different cancer cell lines. The compounds isolated and identified by chromatography and spectroscopic analysis were stigmasterol, ethyl gallate and gallic acid. Cytotoxic assays on cancer cells showed different ranges of activities. A differential effect on cell cycle progression was observed by flow cytometry. In particular, ethyl gallate and tannic acid induced G2/M phase cell cycle arrest and showed interesting effect on microtubule stabilization in Hep3B cells observed by immunofluorescence. The induction of apoptosis was characterized by morphological characteristic changes, and was supported by increases in the ratio of Bax/Bcl-2 expression and activation of caspase 3/7. This work constitutes the first phytochemical and cytotoxic study of C. coriaria and showed the action of its phenolic constituents on cell cycle, cell death and microtubules organization.

The demand for metallic nanoparticles synthesized using green methods has increased due to their various therapeutic and clinical applications, and plant biotechnology may be a potential resource facilitating sustainable methods of AgNPs synthesis. In this study, we evaluate the capacity of extracts from Randia aculeata cell suspension culture (CSC) in the synthesis of AgNPs at different pH values, and their activity against pathogenic bacteria and cancer cells was evaluated. Using aqueous CSC extracts, AgNPs were synthesized with 10% (w/v) of fresh biomass and AgNO3 (1 mM) at a ratio of 1:1 for 24 h of incubation and constant agitation. UV-vis analysis showed a high concentration of AgNPs as the pH increased, and TEM analysis showed polydisperse nanoparticles with sizes from 10 to 90 nm. Moreover, CSC extracts produce reducing agents such as phenolic compounds (162.2 ± 27.9 mg gallic acid equivalent/100 g biomass) and flavonoids (122.07 ± 8.2 mg quercetin equivalent/100 g biomass). Notably, AgNPs had strong activity against E. coli, S. pyogenes, P. aeruginosa, S. aureus, and S. typhimurium, mainly with AgNPs at pH 6 (MIC: 1.6 to 3.9 µg/mL). AgNPs at pH 6 and 10 had a high antiproliferative effect on cancer cells (IC50 < 5.7 µg/mL). Therefore, the use of cell suspension cultures may be a sustainable option for the green synthesis of AgNPs.