Resina Draconis extract exerts anti-HCC effects through METTL3-m6A-Survivin axis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Herbal medicines have become an important treasure reservoir for anti-HCC drugs because of their high efficiency and low toxicity. Herein, we investigated whether a 75% ethanol extract from Resina Draconis (ERD) exhibited comprehensive anti-HCC effects both in vivo and in vitro. We revealed that ERD effectively inhibited proliferation and triggered apoptosis of HCC cells in a dose- and time-dependent maner, posing no apparent apoptotic toxicity to normal liver cells. Moreover, ERD significantly inhibited the migration, invasion and metastasis of HCC cells. Importantly, ERD treatment effectively inhibited the growth of xenograft HCC in nude mice with low toxicity and low side effects. Molecular mechanism analysis showed that ERD strongly reduced the expression of anti-apoptotic protein Survivin, ultimately leading to the cleavage activation of apoptosis executive proteins such as Caspase 3 and Poly (ADP-ribose) polymerase (PARP). Survivin gene silencing apparently sensitized the apoptotic effect induced by ERD. Further experiments revealed that ERD inhibited N6-methyladenosine (m6 A) modification in Survivin mRNA by downregulating Methyltransferase-like 3 (METTL3) expression and reducing the binding rate of METTL3 and Survivin mRNA. Together, our findings suggest that ERD can be severed as a novel anti-HCC natural product by targeting METTL3-m6 A-Survivin axis.

Foeniculum vulgare seed extract induces apoptosis in lung cancer cells partly through the down-regulation of Bcl-2.

The factors behind the pathogenesis of lung cancer are not clear, and treatment failure is generally caused by drug resistance, recurrence, and metastasis. Development of new therapeutic agents to overcome drug-resistance remains a challenge clinically. Various extracts of Foeniculum vulgare have shown promising anticancer activity; however, effects on lung cancer and the underlying molecular mechanisms of action are not clear. In the present study, we found that the ethanol extract of Foeniculum vulgare seeds (EEFS) significantly reduced lung cancer cell growth in vitro and in vivo. EEFS decreased the viability of and triggered apoptosis in the lung cancer cell lines NCI-H446 and NCI-H661. EEFS induced apoptosis mainly through inhibition of Bcl-2 protein expression, reduction of mitochondrial membrane potential, and release of Cytochrome C. Moreover, EEFS significantly inhibited colony formation and cell migration in lung cancer cells. EEFS also effectively inhibited the growth of xenograft tumors derived from NCI-446 cells by reducing Bcl-2 protein expression and inducing apoptosis. Taken together, these findings suggest that EEFS exerts anti-lung cancer activity by targeting the Bcl-2 protein and may have potential as a therapeutic drug for lung cancer.

Foeniculum vulgare seed extract exerts anti-cancer effects on hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The prognosis of HCC is very poor due to the absence of symptoms and a lack of effective treatments. Studies have shown that various Foeniculum vulgare (fennel) extracts exhibit anti-cancer effects on malignant tumors such as skin cancer and prostate cancer. However, the anti-tumor activity of Foeniculum vulgare and its underlying molecular mechanisms towards HCC are unknown. Here, we provide fundamental evidence to show that the 75% ethanol extract of Foeniculum vulgare seeds (FVE) reduced cell viability, induced apoptosis, and effectively inhibited cell migration in HCC cells in vitro. HCC xenograft studies in nude mice showed that FVE significantly inhibited HCC growth in vivo. Mechanistic analyses showed that FVE reduced survivin protein levels and triggered mitochondrial toxicity, subsequently inducing caspase-3 activation and apoptosis. Survivin inhibition effectively sensitized HCC cells to FVE-induced apoptosis. Moreover, FVE did not induce a decrease in survivin or apoptotic toxicity in normal liver cells. Collectively, in vivo and in vitro results suggest that FVE exerts inhibitory effects in HCC by targeting the oncoprotein survivin, suggesting FVE may be a potential anti-cancer agent that may benefit patients with HCC.