Molecular mechanisms of action and chemosensitization of tumor cells in ovarian cancer by phytochemicals: A narrative review on pre-clinical and clinical studies.

Ovarian cancer is the second-leading cause of death among women with cancer of the genital tract. Currently, drugs derived from platinum and taxanes constitute the majority of ovarian cancer treatments. Patients undergoing this chemotherapy are susceptible to cumulative toxic effects and resistance to chemotherapy. Therefore, it is crucial to identify treatment options that are both more effective and better tolerated by patients. Phytochemicals in this context are plant-derived chemicals with antitumor activity that can be used as therapeutic or adjuvant agents in the treatment of ovarian cancer. Consequently, the purpose of this literature review is to demonstrate through existing pre-clinical and clinical trials the potential of phytochemicals in the treatment of ovarian cancer, the mechanisms of action involved, and to contribute to the development of new therapeutic options for ovarian cancer. For this review, the databases PubMed, Scopus, Science Direct, and ClinicalTrials.gov were queried between 2010 and 2022 using terms such as "ovarian cancer," "phytochemicals," "phenolic compounds," "terpenes," and "alkaloids." The present review summarized the possible molecular mechanisms of action by which phytochemicals, such as phenolic acids, flavonoids, diterpenes, triterpenes, saponins, and alkaloids, inhibit this type of cancer, specifically the ability of phytochemicals to induce cell growth regulation, apoptosis, oxidative stress reduction, anti-angiogenesis, and chemosensitization of tumors in ovarian cancer. As their action and cellular mechanism have already been demonstrated in several pre-clinical trials, the phytochemicals identified in our study have the potential to be investigated for the treatment of ovarian cancer. Through pre-clinical and clinical trials, our study demonstrates the potential of phytochemicals in the treatment of ovarian cancer, contributing to the development of novel therapeutic options for ovarian cancer.

Use of Stingless Bee Propolis and Geopropolis against Cancer-A Literature Review of Preclinical Studies.

Cancer is one of the major maladies affecting humankind and remains one of the leading causes of death worldwide. The investigation of the biological activities of stingless bee products, especially propolis and geopropolis, has revealed promising therapeutic properties, especially in the research on new antineoplastic agents. This literature review of preclinical trials, involving biological assays of antitumor activity and identification of the chemical composition of propolis and geopropolis of stingless bee species, describes the cytotoxicity in tumor lineages (breast, lung, ovarian, liver, mouth, pharynx, larynx, colon, stomach, colorectal, cervix, kidney, prostate, melanoma, human glioblastoma, canine osteosarcoma, erythroleukemia, human chronic myelocytic leukemia, and human promyelocytic leukemia) of propolis and geopropolis of 33 species of stingless bees. The chemical composition of propolis and geopropolis was identified, indicating that these belong to the chemical classes of phenolic acids, flavonoids, coumarins, benzophenones, anthraquinones, alkaloids, terpenes, steroids, saponins, fatty acids, and carbohydrates and are possibly responsible for the cytotoxicity in tumor cells. Apoptosis was one of the main mechanisms of cytotoxicity of extracts and substances isolated from stingless bee products. Although the results found are encouraging, other preclinical studies and clinical trials are essential for the discovery of new anticancer agents.

Cytotoxicity and Pro-Apoptotic, Antioxidant and Anti-Inflammatory Activities of Geopropolis Produced by the Stingless Bee Melipona fasciculata Smith.

Geopropolis is produced by some stingless bee species, such as Melipona fasciculata Smith, a native species from Brazil. This study aims to investigate the antioxidant and anti-inflammatory activities and cytotoxicity effects of geopropolis hydroethanolic extracts against lung (H460 and A549) and ovarian (A2780 and ES2) cancer cell lines and non-tumor (HUVEC) cell lines using chemical identification by LC/MS/MS analysis and in silico assays to determine which compounds are associated with bioactivity. The antioxidant activity of extracts and inhibitory activity against COX enzymes were assessed by in vitro assays; cytotoxicity effect was evaluated by the MTT assay; cell cycle was assessed by flow cytometry and apoptosis by Western blotting. The geopropolis extracts showed great radical scavenging potential, preferential inhibition of COX-2, decreased cancer cell viability, non-cytotoxic effects against the non-tumoral cell line, besides modulating the cell cycle and inducing cancer cell apoptosis through the activation of caspase-3 and PARP protein cleavage. The in silico study suggests that corilagin, typhaneoside, taraxerone and marsformosanone, identified by LC/MS/MS, can be associated with anti-inflammatory activity and cytotoxic effects. Thus, the current study suggests the potential of geopropolis concerning the research field of new pharmacological alternatives regarding cancer therapy.

Anti-Inflammatory and Antioxidant Activity of Pollen Extract Collected by Scaptotrigona affinis postica: in silico, in vitro, and in vivo Studies.

Bees are of great importance for plant diversity for being an important pollinating agents. Stingless bees such as Scaptotrigona affinis postica, is cultivated largely due to the products offered by it. Pollen is one of these products, which has been highlighted for exhibit various therapeutic properties. Considering the bioactivity of this natural product, this study investigated the antioxidant, anti-inflammatory, antinociceptive activities, and elucidated the chemical composition of pollen collected extract by Scaptotrigona affinis postica. Using in vitro assays, the antioxidant potential and inhibitory activity against the COX enzyme from pollen extract was evaluated. Additionally, tests were performed to measure the anti-inflammatory and antinociceptive activities in animal models. In our results, we found that pollen extract showed antioxidant effects and inhibitory activity against the COX enzyme. The in vivo assays showed that the extract acts on the nervous system in local and systemic levels and that the anti-inflammatory activity is due the prostanoids reducing. Chemical analyses recognize 10 molecules in the extract belonging to the polyphenol and flavonoids classes and the computational study suggests that is responsible for the observed results. Thus, it is reported for the first time the biological potential of S. aff. postica pollen extract and we conclude that this bee product can be considered as one source of potential new drugs.

Anti-Inflammatory and Antinociceptive Activity of Pollen Extract Collected by Stingless Bee Melipona fasciculata.

The stingless bee, Melipona fasciculata Smith (Apidae, Meliponini), is a native species from Brazil. Their products have high biotechnological potential, however there are no studies about the biological activities of pollen collected by M. fasciculata. In this context, the present study investigated the chemical composition, anti-oxidant, anti-inflammatory, and analgesic activities of hydroethanolic pollen extracts collected by M. fasciculata in three cities in Maranhão State, Brazil. We verified the antioxidant activity of the extracts and inhibitory activity against the cyclooxygenase enzyme using in vitro assays and in allowed to select the extract with higher efficiency to be used on in vivo assays. In these trials, the selected extract showed high anti-inflammatory activity as well as nociceptive effects at central and peripheral level, suggesting that this extract acts on inhibition of histamine release and decreased synthesis of prostaglandins and the in-silico study suggested that polyphenols and acids fatty acids in the extract may be associated with these activities. The results of the present study report the high biological potential of pollen extract and we conclude that the pollen collected by M. fasciculata can be considered as the object of research for new pharmacological alternatives.