Cucurmosin induces apoptosis of BxPC-3 human pancreatic cancer cells via inactivation of the EGFR signaling pathway

Abstract

Abstract. Pancreatic cancer remains the fourth most common cause of cancer-related death in the United States. Potent therapeutic strategies are urgently needed for pancreatic cancer. Cucurmosin is a novel type 1 ribosome-inactivating protein (RIP) isolated from the sarcocarp of Cucurbita moschata (pumpkin). Due to its cytotoxicity, cucurmosin can inhibit tumor cell proliferation through induction of apoptosis on tumor cells, but the specific mechanism is still unclear. We explored the function of cucurmosin in BxPC-3 pancreatic cancer cells using multiple cellular and molecular approaches such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry, reverse transcription polymerase chain reaction (RT-PCR), Western blotting and transmission electron microscopy for observing typical changes and formation of apoptotic bodies. We found that cucurmosin inhibited the proliferation of BxPC-3 cells in a time-and dose-dependent manner, and increased the cell population in the G0-G1 phase. With increasing concentration of cucurmosin, the expression of EGFR, p-PI3K, Akt, p-Akt, mTOR, p-mTOR, P70S6K-α, p-P70S6K-α, 4E-BP1 and p-4E-BP1 at the protein level was decreased, whereas the expression of p-Bad and caspase-9 was elevated. However, the mRNA expression of EGFR did not change. These findings suggest that cucurmosin can downregulate the expression of EGFR by targeting. Cucurmosin induces the apoptosis of BxPC-3 pancreatic cancer cells via the PI3K/Akt/mTOR signaling pathway.

Pumpkin (Cucurbita moschata) Fruit Extract Improves Physical Fatigue and Exercise Performance in Mice

“…These studies demonstrated that C . moschata has extensive bioactivities, such as hepatoprotection [ 5 ], anti-diabetes [ 6 ], anti-cancer [ 7 ], and anti-obesity properties [ 8 ]. Although more detailed and clinical studies are needed to confirm the medicinal effects in light of rational bioactivity function, C .…”

Tendril extract of Cucurbita moschata suppresses NLRP3 inflammasome activation in murine macrophages and human trophoblast cells

“…Increased levels of IL-1β have a detrimental effect on pregnancy, leading to complications such as chorioamnionitis, preeclampsia, and preterm birth [47][48][49][50]. CMD has been widely used in traditional herbal remedies and foods and has received considerable attention due to its extensive bioactivity as an anti-diabetic [51], anti-cancer [52], anti-obesity [53], and anti-inflammatory agent [35]. However, the efficacy of TCMD has not been fully understood.…”

Medicinal bioactivites and allergenic properties of pumpkin seeds: review upon a pediatric food anaphylaxis case report

“…Because of their antimutagenic and immunomodulatory activity, pumpkin seeds have also been associated with lower risk of gastric, breast, lung, prostate and colorectal cancers (6,17,19,20). The ribosome-inactivating proteins Moschatin and Cucurmosin from the mature seeds of pumpkin (C. moschata) were reported to inhibit melanoma cell proliferation as well as leukemia, lung adenocarcinoma and pancreas cancer cell proliferation for the latter (21)(22)(23). Pumpkin albumin 2 S was shown to exhibit a strong anticancer activity toward breast adenocarcinoma (MCF-7), ovarian teratocarcinoma (PA-1), prostate cancer (PC-3 and DU-145) and hepatocellular carcinoma (HepG2) cell lines (17).…”