Background: Cancer stem cells (CSCs) are considered as the origin of tumor relapse. Here, we investigated the effects of Fructus Viticis total flavonoids (FVTF) on the characteristics of lung cancer stem-like cells (LCSLCs) derived from human small cell lung cancer NCI-H446 cell line and its potential mechanism. Methods: Human small cell lung cancer NCI-H446 cell line was cultured in vitro. The CD133 ⁺ cells were sorted from NCI-H446 cell line by magnetic separation. The suspended culture with stem cell-conditioned medium was used to amplify CD133 ⁺ sphere-forming cells (SFCs). The stem cell characteristics of CD133 ⁺ SFCs were evaluated using cell self-renewal capacity by tumor sphere formation assay, migration and invasion capacity by Transwell assay, tumorigenicity by xenograft model in nude mouse and cancer stem cell markers expression levels by western blot. The effects of FVTF on the properties of LCSLCs were examined by tumorsphere formation assay and transwell chamber assay. The expression level of p-Akt was determined by western blot analysis. Result: CD133 ⁺ SFCs derived from human small cell lung cancer NCI-H446 cells exhibited stemness properties of tumorsphere formation and tumorigenesis capacity comparing to the parental cells. FVTF relative selectively inhibited the proliferation of LCSLCs, suppressed tumor sphere forming capacity and migration and invasion of LCSLCs, and down-regulated the protein expression of stem cell markers (CD133, CD44 and ALDH1), self-renewal associated transcription factors (Bmi1, Nanog and OCT4) and invasion associated transcription factors (Twist1 and Snail1) in a dose-dependent manner. Moreover, we found that FVTF treatment could significantly decrease the phosphorylation level of Akt in LCSLCs. Meanwhile, LY294002 and FVTF synergistically inhibited the characteristics of LCSLCs. Conclusion: FVTF inhibits the characteristics of LCSLCs through down-regulating expression of p-Akt.

A novel synthetic derivative of quercetin, 8-trifluoromethyl- 3,5,7,3′,4′- O -pentamethyl-quercetin, inhibits bladder cancer growth by targeting the AMPK/mTOR signaling pathway A novel synthetic derivative of quercetin, 8-trifluoromethyl-3,5,7,3′,4′-O-pentamethyl-quercetin, inhibits bladder cancer growth by targeting the AMPK/mTOR signaling pathway

Cancer remains a leading global health challenge, necessitating the exploration of novel therapeutic strategies. Vitexin (apigenin-8-C-β-D-glucopyranoside), a natural flavonoid glycoside with a molecular weight of 432.38 g/mol, is derived from plants such as mung bean, beetroot, and hawthorn. This compound features a distinctive C-glycosidic bond at the 8-position of its apigenin backbone, contributing to its enhanced metabolic stability compared to O-glycosidic flavonoids. Preclinical studies demonstrate that vitexin modulates critical cellular processes such as cell cycle progression, apoptosis, autophagy, metastasis, angiogenesis, epigenetic modifications, and tumor glycolysis inhibition. It exerts its effects by targeting key signaling pathways, including phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/Akt/mTOR), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and signal transducer and activator of transcription 3 (STAT3), and shows potential for combination therapies to enhance efficacy and overcome resistance. Advances in nanotechnology further enhance its bioavailability and delivery potential. This review comprehensively examines the current evidence on vitexin’s anticancer mechanisms, highlighting its multi-target therapeutic potential and future research directions.

Breast cancer (BC) is a significant public health concern globally. Triple-negative breast cancer (TNBC) is considered the most challenging type, as it is defined by an absence of estrogen and progesterone receptor expression, along with a lack of HER2 overexpression. In the current study, we developed a novel thymoquinone (TQ), TQFL19, to control TNBC progression. Purpose: The current study aimed to investigate the anticancer potential of a newly synthesized TQFL19 against TNBC. Study design: To achieve our research goals, we meticulously developed both in vitro and in vivo studies focused on TNBC cell growth, metastasis, and invasion. Results: Characterization and ADMET properties prediction of TQFL19 were first performed before treating TNBC cells. TQFL19 exhibited more potent cytotoxicity than TQ against 4T1, BT-549, and MDA-MB-231 cells and induced apoptosis of 4T1 and MDA-MB-231, besides cell cycle arrest of MDA-MB-231. In vivo mice allograft of 4T1 revealed the ability of TQFL19 to hinder the growth, migration, and metastasis of TNBC cells. Conclusions: The results suggest that TQFL19 potentially inhibited TNBC growth, metastasis, and invasion. The results conclude that TQFL19 could be a viable candidate for TNBC therapy.