Pyrones isolated from Annona acutiflora exhibit promising cytotoxic effects on cancer cell lines.

This work discusses the ongoing challenge of cancer, focusing on therapy issues such as chemotherapy resistance and adverse drug effects. It emphasizes the need for new anticancer agents with improved efficacy and fewer side effects, exploring natural products from plant sources. The Annonaceae family, specifically the Annona genus, is highlighted for its medicinal properties, including anti-inflammatory and anticancer effects. The study focuses on the isolation and elucidation of the substances present in Annona acutiflora leaves. The methodology involves chromatographic and spectroscopy techniques. The isolated compounds, (6S)-5'-oxohepten-1'E,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (1), (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (2) and (6R)-5'-oxohepten-1'Z,3'E-dienyl)-5,6-dihydro-2H-pyran-2-one (3) were investigated for cytotoxicity assays on cancer cell lines and normal cells. Results show promising cytotoxic activity, particularly with compound 3, demonstrating potential activity against oral cancer (43.18µM), hepatocarcinoma (17.24µM), melanoma (5.39µM), and colon cancer (59.03µM). The compound outperforms carboplatin in selectivity against oral cancer (S.I. 2.15) and melanoma (S.I. 17.22). The study concludes by suggesting the potential of these α-pyrones as effective and less toxic alternatives for cancer therapy.

A Novel MDM2-Binding Chalcone Induces Apoptosis of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) represents ~90% of all oral cancers, being the eighth most common cancer in men. The overall 5-year survival rate is only 39% for metastatic cancers, and currently used chemotherapeutics can cause important side effects. Thus, there is an urgency in developing new and effective anti-cancer agents. As both chalcones and 1,2,3-triazoles are valuable pharmacophores/privileged structures in the search for anticancer compounds, in this work, new 1,2,3-triazole-chalcone hybrids were synthesized and evaluated against oral squamous cell carcinoma. By using different in silico, in vitro, and in vivo approaches, we demonstrated that compound 1f has great cytotoxicity and selectivity against OSCC (higher than carboplatin and doxorubicin) and other cancer cells in addition to showing minimal toxicity in mice. Furthermore, we demonstrate that induced cell death occurs by apoptosis and cell cycle arrest at the G2/M phase. Moreover, we found that 1f has a potential affinity for MDM2 protein, similar to the known ligand nutlin-3, and presents a better selectivity, pharmacological profile, and potential to be orally absorbed and is not a substrate of Pg-P when compared to nutlin-3. Therefore, we conclude that 1f is a good lead for a new chemotherapeutic drug against OSCC and possibly other types of cancers.

New substances of Equisetum hyemale L. extracts and their in vivo antitumoral effect against oral squamous cell carcinoma.

ETHNOBOTANICAL RELEVANCE: Equisetum hyemale is used in traditional medicine as an anti-inflammatory, antioxidant, diuretic and anticancer agent. Recent studies have observed antiproliferative activity of this species in some tumor cell lines. AIM OF THE STUDY: The aim of this study was to evaluate the antiproliferative activity of the ethanol extract of E. hyemale and its partitions in oral squamous carcinoma cell lines, the death pathways induced by the most active partition, the acute toxicity and therapeutic activity, and the identification of the main compounds. MATERIALS AND METHODS: The ethanol crude extract was prepared from the stems of E. hyemale and partitions were obtained from this extract with n-hexane, dichloromethane and ethyl acetate. Cytotoxicity assays were performed using MTT on human oral tumor lines SCC-9, SCC4 and SCC-25, and normal primary fibroblasts. The main pathways of programmed cell death were analyzed. Acute toxicity in mice was performed using the most active partition, ethyl acetate. Antitumor activity was accessed in xenotransplants grafts of SCC-9 cells in Balb/nude mice. Phytochemical analysis was performed using UHPLC-MS/MS and dereplication was done using Global Natural Product Social Molecular Networking (GNPS) analysis. RESULTS: Ethanol extract, n-hexane and ethyl acetate partitions showed dose-dependent activity and selectivity towards oral tumor cells, with the ethyl acetate being the most bioactive. This medium polarity partition was shown to induce tumor cell death through apoptosis due to the presence of activated caspase 3/7, DNA fragmentation, chromatin condensation and phosphatidylserine exposure. The ethyl acetate partition also produced low toxicity in mice, provoking mild hepatic changes, but without causing necrosis and significantly reduced tumors volume and weight in xenotransplants of SCC-9 cells. Phytochemical analysis allowed identification of kaempferol glycosides and cinnamic acid derivatives previously described for E. hyemale. In addition it was possible to identify 6 new non-glycolyzed flavonoids 5-Hydroxy-3',4',7,8-tetramethoxyflavone (14), 5,4'-Dihydroxy-7,8,3'-trimethoxyflavone (15), 5,7-Dihydroxy-3',4'-dimethoxyflavone (16), 3',4,5,7-Tretramethoxyflavone (17), 5-Hydroxy-3'4',7-trimethoxyflavone (18), and 5,4'-Dihydroxy-3'-7'-dimethoxyflavone (19); besides 5 compounds already determined to be cytotoxic in other species, Isoferulic acid (1), Ferulic acid (2), Atractylenolide III (6), Dihydroxy-3',4'-dimethoxyflavone (16), and 5-Hydroxy-3'4 ',7-trimethoxyflavone (18). CONCLUSION: The results indicate that the E. hyemale extract and partitions inhibited 3 different cell lines of OSCC in a highly selective nontoxic way by inducing apoptosis of the cells. We identified 6 new non-glycosylated flavonoids and 5 other substances in this species.

Cytotoxic effect of pure compounds from Piper rivinoides Kunth against oral squamous cell carcinoma.

The oral squamous cell carcinoma (OSCC) is the eighth more common cancer in men. The development of new and more efficient drugs is needed. Plants of the genus Piper are popularly used in the treatment of many diseases. This study evaluated the antitumor effect of extract, fraction and isolated compounds from leaves of P. rivinoides in oral cancer. The isolated compounds (conocarpan, eupomatenoid-5 and eupomatenoid-6) were effective in inducing cell death in OSCC cell lines (SCC4, SCC9 and SCC25) compared to the standard chemotherapeutic agent carboplatin, and this effect was time-dependent. Conocarpan was more selective and stable than eupomatenoid-5 and eupomatenoid-6, resembling the stability of carboplatin. There was a significant presence of pyknotic nuclei and active caspase-3 expression under conocarpan treatment, suggesting cell death through apoptosis. In conclusion, conocarpan was the most effective compound against OSCC cells and might be considered for future cancer studies.