The natural compound sulforaphene, as a novel anticancer reagent, targeting PI3K-AKT signaling pathway in lung cancer

Abstract

Lung cancer is one of the leading causes of cancer death worldwide. Isothiocyanates from cruciferous vegetables been shown to possess anticarcinogenic activities in lung malignances. We previously found sulforaphene (4-methylsufinyl-3-butenyl isothiocyanate, SFE), one new kind of isothiocyanates, existing in a relative high abundance in radish seeds. An efficient methodology based on macroporous resin and preparative high-performance liquid chromatography was developed to isolate SFE in reasonably large quantities, high purity and low cost. However, it is still largely unclear whether SFE could function as an antineoplastic compound, especially in lung cancer. In this study, we systematically investigated the anti-cancer effects of SFE in vitro as well as its possible underling molecular mechanisms in lung cancer. The acute toxicity tests and pharmacokinetics tests for SFE were performed to evaluate its drugability in mice. Also, we evaluated the in vivo anti-cancer effects of SFE using nude Balb/C mice with lung cancer xenograft. SFE can induce apoptosis of multiple lung cancer celllines and, thus, inhibited cancer cell proliferation. Lung cancer cells treated with SFE exhibit significant inhibition of the PI3K-AKT signaling pathway, including depressed PTEN expression and inhibition of AKT phosphoralation. At well-tolerated doses, administration of SFE to mice bearing lung cancer xenografts leads to significant inhibitions of tumor growth. In summary, our work identifies SFE as a novel natural broad-spectrum small molecule inhibitor for lung cancer.

Apoptosis induction by Pleurotus sajor-caju (Fr.) Singer extracts on colorectal cancer cell lines

“…These results suggest that the PSC-hex components disrupt multiple tumoral signaling pathways, including growth arrest (associated to proteins p21 and p53) and/or apoptosis pathways (associated to proteins Bax, Bcl-2 and p53). These results are in line with recent findings, showed that many natural compounds found in mushrooms have pro-apoptotic activities (Yang et al, 2016). Moreover, literature supports that mushroom constituents such as sterols may contribute to the antitumoral effects observed in this study (Heleno et al, 2015).…”

A formulation of pancreatic pro-enzymes provides potent anti-tumour efficacy: a pilot study focused on pancreatic and ovarian cancer

“…Intra venous injection of the pro-enzymes resulted in maximum detectable levels in plasma at 15–30 min that decline in the first hour and were still present in low levels after three hours post-dose. These observations are similar to time-concentration profiles found in previous pharmacokinetic studies with potential therapeutic agents for human cancers, including pancreas 37 , 38 and also in current chemotherapeutics used in the clinic such as gemcitabine 39 . Moreover, examination of the tissue distribution demonstrated that proenzymes perfused into organs, including the heart, liver, spleen, lung, kidney and entire gastrointestinal tract which indicated a wide tissue distribution of the pro-enzymes 40 .…”

Cucurbitacin D Overcomes Gefitinib Resistance by Blocking EGF Binding to EGFR and Inducing Cell Death in NSCLCs

“…Naturally occurring dietary compounds have increased the interest in the prevention of various types of cancers (14)(15)(16), including lung cancer (17)(18)(19)(20). Cucurbitacin is commonly found in the cucurbitaceae family and has been used in traditional medicine (21).…”