Correction: Salehi et al. Cucurbits Plants: A Key Emphasis to Its Pharmacological Potential. Molecules 2019, 24, 1854

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There was an error in the original publication [1]. Section 4.2. Anticancer Activities of Cucurbita Plants, contained uncommon terminology and linguistic inconsistencies that affected clarity and readability. This section has been thoroughly revised to improve clarity, accuracy, and adherence to standard scientific language while maintaining the original meaning. This revision was carried out with the assistance of a native English-speaking medical expert to ensure precise and appropriate terminology.

A correction has been made to Section 4.2. Anticancer Activities of Cucurbita Plants. The corrected text is as follows:

4.2. Anticancer Activities of Cucurbita Plants

Cucurbitacins are a distinct class of triterpenoids characterized by a cucurbitane-based structure, which contributes to their diverse biological activities, particularly their anticancer potential. Cucurbitacins have been identified as major secondary metabolites within the Cucurbitaceae family. They possess a biogenetically derived 10α-cucurbit-5-ene [19(10→19β) abeo-10α-lanostane] skeleton, which is closely linked to their cytotoxic effects. Several studies have attributed both in vitro and in vivo cytotoxic effects to cucurbitacins [79,80]. Jayaprakasam et al. [81] demonstrated the anticancer properties of cucurbitacins B, D, E and I, isolated from Cucurbita andreana Naudin, against colon, breast, lung, and central nervous system cancer cell lines. Among these, cucurbitacin B has been extensively investigated, with multiple studies confirming its efficacy in various cancer models, including in vivo tumor xenografts [82–85]. The precise mechanisms underlying its anticancer activity remain debated. The suppression of the oncogene Signal Transducer and Activator of Transcription 3 (STAT3) appears to play a key role in tumor growth inhibition [86], although alternative mechanisms may also contribute. Cancer remains a leading cause of mortality, accounting for approximately 12% of global deaths. Current therapeutic options include chemotherapy, surgical interventions, and radiation therapy. However, chemotherapy is often limited by drug resistance, toxicity, side effects, and insufficient selectivity for tumor cells [87]. Consequently, there is significant interest in exploring plant-derived bioactive compounds as promising sources for novel anticancer agents.

In Vitro Anticancer/Antitumor Effects

To date, over forty cucurbitacins have been isolated from the Cucurbitaceae family and other related medicinal plants. The proapoptotic effects of cucurbitacins are attributed to their ability to modulate gene expression, transcriptional activity via nuclear signaling, and mitochondrial membrane potential. Additionally, cucurbitacins can either activate or inhibit key apoptotic regulators. They are potent inhibitors of the JAK/STAT signaling pathway and also impact alternative apoptotic pathways, including PARP cleavage, MAPK signaling, and caspase-3 activation. Cucurbitacins have been shown to downregulate JAK3 and pSTAT3 levels, as well as several STAT3-regulated proteins involved in cell cycle progression, such as Bcl-2, Mcl-1, cyclin D3, and Bcl-xL [88]. C. pepo alcohol extract demonstrated cytotoxic activity against HepG2 and CT26 cancer cell lines, with IC_50_ values of 132.6 µg/mL and 167.2 µg/mL, respectively. Similarly, the ethanol extract of C. pepo exhibited a dose-dependent inhibitory effect on HeLa cell proliferation [89]. Cucurbita glycosides A and B, isolated from C. pepo ethanol extract, exhibited cytotoxic activity in vitro against HeLa cells, with IC_50_ values of 17.2 µg/mL and 28.5 µg/mL, respectively [90]. Cucurbitacins B and E, isolated from C. pepo cv dayangua, demonstrated antiproliferative effects against MCF-7, HCT-116, SF-268, A549, and NCI-H460 cancer cell lines [81]. The antiproliferative effects of 23,24-dihydrocucurbitacin F on human prostate cancer (PCa) cells may be attributed to the induction of cofilin–actin rod formation, leading to actin aggregation, cytokinesis failure, and cell cycle arrest at the G2/M phase, followed by apoptosis [91]. Furthermore, 23,24-dihydrocucurbitacin F has been shown to inhibit Epstein–Barr virus activation, induced by the tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA), and exerts significant antitumor-promoting effects in murine skin cancer models [88].

Treatment with cucurbitacins B and E resulted in apoptosis and cell cycle arrest in MDA-MB-231 and MCF-7 breast cancer cell lines. Additionally, these compounds modulated the expression of proteins involved in cell cycle regulation in both estrogen-independent (MDA-MB-231) and estrogen-dependent (MCF-7) human breast cancer cell lines. Cucurbitacin B was found to inhibit tumor growth and exert cytotoxic effects on SKBR-3 and MCF-7 breast cancer cell lines, primarily through G2/M phase arrest and apoptosis. Cucurbitacin B treatment also downregulated the expression of Cyclin D1, c-Myc, and β-catenin and prevented the nuclear translocation of β-catenin and galectin-3. Western blot analysis revealed increased PARP cleavage, suggesting caspase activation, and a reduction in Wnt signaling-related proteins such as galectin-3, β-catenin, c-Myc, and cyclin D1, along with modifications in phosphorylated GSK-3β levels [92].

Cucurbitacin E disrupted the cytoskeletal architecture of actin and vimentin, thereby inhibiting prostate cancer cell proliferation. Additionally, cucurbitacins suppressed endothelial cell proliferation by disrupting F-actin and tubulin microfilaments. Moreover, they exhibited antiangiogenic and antimetastatic properties by reducing T-lymphocyte proliferation and cellular motility [93]. Current research suggests that secondary metabolites from C. pepo possess significant anticancer activity, highlighting their potential role in the development of novel chemotherapeutic agents for tumor prevention and treatment.