Pharmacological basis and new insights of deguelin concerning its anticancer effects.

Deguelin is a rotenoid of the flavonoid family, which can be extracted from Lonchocarpus, Derris, or Tephrosia. It possesses the inhibition of cancer cell proliferation by inducing apoptosis through regulating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, the NF-κB signaling pathway, the Wnt signaling pathway, the adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway and epidermal growth factor receptor (EGFR) signaling, activating the p38 mitogen-activated protein kinase (MAPK) pathway, repression of Bmi1, targeting cyclooxygenase-2 (COX-2), targeting galectin-1, promotion of glycogen synthase kinase-3ß (GSK3ß)/FBW7-mediated Mcl-1 destabilization and targeting mitochondria via down-regulating Hexokinases II-mediated glycolysis, PUMA-mediation, which are some crucial molecules which modulate closely cancer cell growth and metastasis. Deguelin inhibits tumor cell propagation and malignant transformation through targeting angiogenesis, targeting lymphangiogenesis, targeting focal adhesion kinase (FAK), inhibiting the CtsZ/FAK signaling pathway, targeting epithelial-mesenchymal transition (EMT), the NF-κB signaling pathway, regulating NIMA-related kinase 2 (NEK2). In addition, deguelin possesses other biological activities, such as targeting cell cycle arrest, modulation of autophagy, inhibition of hedgehog pathway, inducing differentiation of mutated NPM1 acute myeloid leukemia etc. Therefore, deguelin is a promising chemopreventive agent for cancer therapy.

Investigating into anti-cancer potential of lycopene: Molecular targets.

Lycopene, the main pigment of tomatoes, possess the strongest antioxidant activity among carotenoids. Lycopene has unique structure and chemical properties. We searched the literature, via PubMed, Embase, Web of Science and Google database so on to screen citations from inception to Oct 2020 for inclusion in this study. We found that as a common phytochemical, it did not attract much attention in the past few years. However, recent studies have indicated that, in addition to antioxidant activity and the second stage of detoxification, the anticancer of lycopene is also considered to be an important determinant of tumor development including the inhibition of cell proliferation, inhibition of cell cycle progression, induction of apoptosis, inhibition of cell invasion, angiogenesis and metastasis. The effect mechanisms of lycopene are related to the regulation of several signal transduction pathways, such as PI3K/Akt pathway, modulation of insulin-like growth factors system, the suppression of activity of sex steroid hormones, the modification of relevant gene expression, and the alteration of mitochondrial function. These novel findings have suggested that lycopene acts as a promising functional natural pigment, and may be associated with a decreased risk of different types of cancer. This review presents the latest knowledge with respect to its molecular mechanisms and its molecular targets of the inhibitory effects on carcinogenesis.

The dual induction of apoptosis and autophagy by SZC014, a synthetic oleanolic acid derivative, in gastric cancer cells via NF-κB pathway.

Oleanolic acid (OA) possesses various pharmacological activities, such as antitumor and anti-inflammation; however, its clinical applications are limited by its relatively weak activities and low bioavailability. In this study, we evaluated the cytotoxic activity of seven novel OA derivatives, one of which, SZC014 [2-(pyrrolidine-1-yl) methyl-3-oxo-olean-12-en-28-oic acid], exhibited the strongest antitumor activity; its anticancer effect on gastric cancer cells and action mechanisms were investigated. The viability of OA and seven synthesized derivatives treating gastric cancer cells was detected using tetrazolium (MTT). Among them, SZC014 exhibited the strongest cytotoxic activity against gastric cancer cells (SGC7901, MGC803, and MKN-45). The effect of SZC014 on cell cycle was identified by propidium iodide (PI) staining assay. The cellular apoptosis induced by SZC014 was tested by annexin V/PI. The cellular morphological changes and ultrastructural structures affected by SZC014 were observed and imaged through inverted phase contrast microscope and transmission electron microscopy. Western blotting was performed to explore the expression of proteins associated with apoptosis (caspase 3, caspase 9, Bax, Bcl-2, and Bcl-xL), autophagy (Beclin 1 and ATG 5), and nuclear factor-κB (NF-κB) signal pathway, respectively. The cytotoxic activities of all the seven synthesized OA derivatives were stronger than that of OA against gastric cancer cells. SZC014 exhibited stronger cytotoxic activity than other OA derivatives, inhibited the proliferation of gastric cancer cells, besides, induced G2/M phase cell cycle arrest in SGC7901 cells. Both apoptosis and autophagy were found simultaneously in SZC014-treated SGC7901 cells. Caspase-dependent apoptosis induced by SZC014 was confirmed to be associated with upregulation of Bax and downregulation of Bcl-2 and Bcl-xL, while upregulation of Beclin 1 and ATG 5 was inferred to be involved in SZC014-induced autophagy. Moreover, treating cells with SZC014 resulted in a decrease in phosphorylation of IκBα and NF-κB/p65 and NF-κB/p65 nuclear translocation. The cytotoxic activities of seven OA derivatives were generally stronger than that of OA, among which, SZC014 possessed the most potent anticancer activity in SGC7901 cells and would be a promising chemotherapic agent for the treatment of gastric cancer.