Hepatocellular carcinoma (HCC) is the third most common cancer in terms of mortality and the sixth in incidence worldwide. Treatment varies by tumor stage, but low survival rates are common across all stages. Due to these poor outcomes, there is a critical need for new treatment options and lead compounds, prompting an active search. Geopropolis has been identified as a source of bioactive compounds with various pharmacological activities, including anticancer effects against different types of cancer. Since stingless bees may be selective for native botanical species, the geopropolis they produce can have an unusual chemical profile. In this study, we report the antioxidant properties and anticancer potential of geopropolis extracts produced by Melipona bicolor, M. marginata, and M. mondury using 2D- and 3D- cell culture models. The chemical profile of these samples using UPLC-QTOF HRMS/MS indicated ferreirin and dihydrokaempferide as the main flavonoids, along with cupressic acid and 15-acetoxyisocupressic acid as the most abundant diterpenoids. Interestingly, artepillin C, a main component of green propolis, was also detected. The geopropolis extracts showed good cell viability inhibition and selectivity indices in comparison to cisplatin used as an HCC treatment option. The antioxidant capacity of the geopropolis extracts was high and correlated with the cytotoxic effect against the HCC cells. Investigations into the mechanisms show the ability of the extracts to induce apoptosis and suppress the clonogenic potential of these cell lines. We also observed an inhibition of spheroid formation, viability, and morphology alterations. This is the first time the effects of geopropolis are described in a panel of HCC cell lines.

Breast cancer stands as one of the foremost cause of cancer-related deaths globally, characterized by its varied molecular subtypes. Each subtype requires a distinct therapeutic strategy. Although advancements in treatment have enhanced patient outcomes, significant hurdles remain, including treatment toxicity and restricted effectiveness. Here, we explore the anticancer potential of novel 1,4-naphthoquinone/4-quinolone hybrids on breast cancer cell lines. The synthesized compounds demonstrated selective cytotoxicity against Luminal and triple-negative breast cancer (TNBC) cells, which represent the two main molecular types of breast cancer that depend most on cytotoxic chemotherapy, with potency comparable to doxorubicin, a standard chemotherapeutic widely used in breast cancer treatment. Notably, these derivatives exhibited superior selectivity indices (SI) when compared to doxorubicin, indicating lower toxicity towards non-tumor MCF10A cells. Compounds 11a and 11b displayed an improvement in IC₅₀ values when compared to their precursor, 1,4-naphthoquinone, for both MCF-7 and MDA-MB-231 and a comparable value to doxorubicin for MCF-7 cells. Also, their SI values were superior to those seen for the two reference compounds for both cell lines tested. Mechanistic studies revealed the ability of the compounds to induce apoptosis and inhibit clonogenic potential. Additionally, the irreversibility of their effects on cell viability underscores their promising therapeutic utility. In 3D-cell culture models, the compounds induced morphological changes indicative of reduced viability, supporting their efficacy in a more physiologically relevant model of study. The pharmacokinetics of the synthesized compounds were predicted using the SwissADME webserver, indicating that these compounds exhibit favorable drug-likeness properties and potential as antitumor agents. Overall, our findings underscore the promise of these hybrid compounds as potential candidates for breast cancer chemotherapy, emphasizing their selectivity and efficacy.