The anticancer effects of Cucurbitacin I inhibited cell growth of human non‑small cell lung cancer through PI3K/AKT/p70S6K pathway

Abstract

The present study aimed to identify potential anticancer effects of Cucurbitacin I regulators on cell growth of human non‑small cell lung cancer (NSCLC) and to explore their mechanism. The results indicated that the anticancer effects of Cucurbitacin I markedly attenuated cell proliferation, and induced apoptosis in NSCLC. Furthermore, Cucurbitacin I suppressed phosphatidylinositol‑4,5‑bisphosphate 3‑kinase (PI3K), phosphorylation (p)‑AKT and p‑p70S6K pathway in NSCLC. Then, (PI3K) inhibitor increased anticancer effects of Cucurbitacin I on NSCLC. In conclusion, the present results indicated that Cucurbitacin I inhibited cell growth of human NSCLC through PI3K/AKT/p70S6K signaling pathway.

Cucurbitacin I induces apoptosis in ovarian cancer cells through oxidative stress and the p190B‑Rac1 signaling axis

“…at present, in addition to surgery, the development of antitumor drugs is also very important. cucurbitacin i has a strong antitumor activity (6,7). cucurbitacin i has been reported to induce death in various types of tumor cells; for example it can induce apoptosis in non-small cell lung cancer cells and osteosarcoma cells by inhibiting the Pi3K/aKT/p70S6K and STaT3 signaling, respectively.…”

“…According to recent findings, cucurbitacin i, which is 1 of 12 variants of cucurbitacins, has demonstrated a potent anticancer effect on non-small cell lung cancer cells (6). cucurbitacin i has been reported to cause cancer cell death by inhibiting multiple signaling pathways, such as the Janus kinase (JaK)/STaT3, Pi3K/aKT/p70S6K and serine/threonine-protein kinase PaK1 (PaK1)/PaK4 pathways (7)(8)(9). However, the underlying mechanism for the anticancer effect of cucurbitacin i is not yet completely understood, and further studies are required to clarify it.…”

A Citrullus colocynthis fruit extract acutely enhances insulin-induced GLUT4 translocation and glucose uptake in adipocytes by increasing PKB phosphorylation

“…It also displays anticancer (Ganesan and Xu, 2017;He et al, 2016), insulinotropic (Folador et al, 2010) and α-glucosidase-inhibiting activity (Choo et al, 2012). Cucurbitacins B, E, I, at prolonged treatment, are all cytotoxic, inhibit STAT3 (Chan et al, 2010;Liu et al, 2020;Oi et al, 2016;Seo et al, 2014), disrupt cytoskeleton organization (Knecht et al, 2010;Sari-Hassoun et al, 2016;Yin et al, 2008), inhibit PKB phosphorylation (Si et al, 2019;Zhou et al, 2017;Zhu et al, 2018), and are particularly studied for their anti-microbial (Hussain et al, 2014) and anti-cancer effects (Garg et al, 2018;Li et al, 2018;Si et al, 2019). Cucurbitacin B was also found to display insulinotropic activity .…”

Cucurbitacin I induces pro‐death autophagy in A549 cells via the ERK‐mTOR‐STAT3 signaling pathway

“…As one of the 12 categories of cucurbitacins, cucurbitacin I, a selective inhibitor of JAK2/STAT3, has a potent anticancer effect on several types of cancer cells, including breast cancer, lung cancer, and glioma, which is comparable to cucurbitacin B and D, both of them suppress the proliferation of a variety of cancer cells in vitro and vivo . The inhibition of JAK/STAT3, PI3K/Akt/p70S6K, or PAK1/PAK4 signaling pathways, were recognized to be involved in the anti‐cancer action of cucurbitacin I. Zhang et al further confirmed that cucurbitacin I induced strong autophagy and autophagic death in cancer cells. In fact, the molecular and cellular mechanisms involved in the induction of cucurbitacin‐I in cancer cell death are very complex, which deserves further study to improve cancer chemotherapy, and reduce potential resistance.…”

“…6,7 As one of the 12 categories of cucurbitacins, cucurbitacin I, a selective inhibitor of JAK2/STAT3, has a potent anticancer effect on several types of cancer cells, including breast cancer, lung cancer, and glioma, which is comparable to cucurbitacin B and D, both of them suppress the proliferation of a variety of cancer cells in vitro and vivo. 8,9 The inhibition of JAK/ STAT3, 10 PI3K/Akt/p70S6K, 11 or PAK1/PAK4 signaling pathways, 12 were recognized to be involved in the anti-cancer Yinyun Ni and Sisi Wu contributed equally to this work and should be considered co-first authors. action of cucurbitacin I. Zhang et al 13 further confirmed that cucurbitacin I induced strong autophagy and autophagic death in cancer cells.…”