Evaluation of carcinogenic substances from the environment is a challenge for scientists. Recently, a novel approach based on 10 key characteristics of human carcinogens classified by the International Agency for Research on Cancer (IARC) has emerged. Carcinogenesis depends on different mechanisms and factors, including genetic, infectious (bacteria, viruses) and environmental (chemicals) factors. Endocrine disruptors are exogenous chemicals that can interfere and impair the function of the endocrine system due to their interaction with estrogen receptors or their estrogen signaling pathways inducing adverse effects in the normal mammary development, originating cancer. They are heterogeneous chemicals and include numerous synthetic substances used worldwide in agriculture, industry and consumer products. The most common are plasticizers, such as bisphenol A (BPA), pesticides, such as dichlorodiphenyltrichloroethane, and polychlorinated biphenyls (PCBs). Xenoestrogens appear to serve an important role in the increased incidence of breast cancer in the United States and numerous other countries. Several studies have demonstrated the role of organochlorine xenoestrogens in breast cancer. Therefore, the overall cumulative exposure of women to estrogens results in an increased risk for this type of cancer. Factors like lifestyle and diet also serve a role in the increased incidence of this disease. The aim of the present study was to analyze these chemical compounds based on the key characteristics given by the IARC, with a special focus on breast cancer, to establish whether these compounds are carcinogens, and to create a model for future analysis of other endocrine disruptors.
Breast cancer is one of the major health issues confronting women; however, treatment with conventional chemotherapeutic drugs is limited. Currently, paclitaxel is used as a therapeutic clinical agent to treat breast cancer that exerts antitumor activity in numerous types of cancer cell. Curcumin (diferuloylmethane), a polyphenol derived from turmeric (Curcuma longa), possesses several properties that could enable it to exert an anticancer effect. Previous reports have demonstrated the synergistic effects of several chemotherapeutic drugs in combination with curcumin. Therefore, the aim of the current study was to evaluate cell death induced by curcumin and paclitaxel alone and in combination in human breast cancer cell lines: MCF7, an epithelial and luminal-like adenocarcinoma cell line triple positive for estrogen and progesterone receptor, and MDA-MB-234, a metastatic human breast cancer cell line triple negative for such receptors, as well as MCF-10F as a normal breast cell line. The results indicated that curcumin and paclitaxel induced apoptosis and necrosis, which was demonstrated through multiple methods, including assays of caspase-3/7 activity, Annexin V, poly(ADP-ribose) polymerase-1 activation and protein expression of caspase-3, nuclear factor (NF)-κB transcription factor and proliferating cell nuclear antigen. The results identified that the combination of curcumin and paclitaxel had a decreased effect on apoptosis in the malignant MDA-MB-231 cell line compared with in MCF7 or MCF-10F. It was demonstrated that the combined treatment with curcumin and paclitaxel resulted in a higher level of apoptosis compared with either substance alone in breast cancer cell lines. Therefore, breast cancer treatment may benefit from the use of a combination of drugs in chemotherapy.
Cervical, anogenital, and some head and neck cancers (HNC) are etiologically associated with high-risk human papillomavirus (HR-HPV) infection, even though additional cofactors are necessary. Epidemiological studies have established that tobacco smoke (TS) is a cofactor for cervical carcinogenesis because women who smoke are more susceptible to cervical cancer when compared to non-smokers. Even though such a relationship has not been established in HPV-related HNC, a group of HPV positive patients with this malignancy are smokers. TS is a complex mixture of more than 4500 chemical compounds and approximately 60 of them show oncogenic properties such as benzo[α]pyrene (BaP) and nitrosamines, among others. Some of these compounds have been evaluated for carcinogenesis through experimental settings in collaboration with HR-HPV. Here, we conducted a comprehensive review of the suggested molecular mechanisms involved in cooperation with both HR-HPV and TS for epithelial carcinogenesis. Furthermore, we propose interaction models in which TS collaborates with HR-HPV to promote epithelial cancer initiation, promotion, and progression. More studies are warranted to clarify interactions between oncogenic viruses and chemical or physical environmental factors for epithelial carcinogenesis.
MicroRNAs (miRNAs) constitute a subclass of non-coding RNAs that exert substantial influence on gene-expression regulation. Their tightly controlled expression plays a pivotal role in various cellular processes, while their dysregulation has been implicated in numerous pathological conditions, including cancer. Among cancers affecting women, breast cancer (BC) is the most prevalent malignant tumor. Extensive investigations have demonstrated distinct expression patterns of miRNAs in normal and malignant breast cells. Consequently, these findings have prompted research efforts towards leveraging miRNAs as diagnostic tools and the development of therapeutic strategies. The aim of this review is to describe the role of miRNAs in BC. We discuss the identification of oncogenic, tumor suppressor and metastatic miRNAs among BC cells, and their impact on tumor progression. We describe the potential of miRNAs as diagnostic and prognostic biomarkers for BC, as well as their role as promising therapeutic targets. Finally, we evaluate the current use of artificial intelligence tools for miRNA analysis and the challenges faced by these new biomedical approaches in its clinical application. The insights presented in this review underscore the promising prospects of utilizing miRNAs as innovative diagnostic, prognostic, and therapeutic tools for the management of BC.