Abstract
Two kinds of naphthalimide derivatives were synthesized and evaluated for in vitro their anti-hepatocellular carcinoma properties. Compound 3a with a fused thiazole fragment to naphthalimide skeleton inhibited cell migration of SMMC-7721 and HepG2, and further in vivo trials with two animal models confirmed that compound 3a moderately inhibited primary H22 tumor growth (52.6%) and potently interrupted lung metastasis (75.7%) without obvious systemic toxicity at the therapeutic dose. Mechanistic research revealed that compound 3a inhibited cancerous liver cell growth mostly by inducing G2/M phase arrest. Western blotting experiments corroborated that 3a could up-regulate the cell cycle related protein expression of cyclin B1, CDK1 and p21, and inhibit cell migration by elevating the E-cadherin and attenuating integrin α6 expression. Our study showed that compound 3a is a valuable lead compound worthy of further investigation.
Highlights
Hepatocellular carcinoma (HCC), the most common malignancy of the liver, is the third most common cause of cancer-related deaths in the world [1,2]
The results showed that polyamine conjugates 3a–e with a 2-aminothiazole group fused to the naphthalimide skeleton were active forof alltarget testedcompounds tumor cells.against
In this study, we found that expression of cyclin B1 and CDK1 were both up-regulated in a we found that expression of cyclin B1 and CDK1 were both up-regulated in a dose-dependent manner dose-dependent manner (Figure 4C,D), which was similar to the effects of 6-methoxy-3-(3′,4′,5′(Figure 4C,D), which was similar to the effects of 6-methoxy-3-(30,40,50 -trimethoxybenzoyl)-1H-indole trimethoxybenzoyl)-1H-indole (BPR0L075) on colorectal cancer cells [35]
Summary
Hepatocellular carcinoma (HCC), the most common malignancy of the liver, is the third most common cause of cancer-related deaths in the world [1,2]. Some feasible and curative measures, including resection and liver transplant, are used in treating HCC. Once patients are diagnosed with HCC, the disease is often already at an advanced stage, and accompanied with micrometastases. In this case, surgical therapy is no longer a curative treatment option. Traditional chemotherapy treatment is irreplaceable and can be used alone or in combination with other therapies. Postoperative chemotherapy might improve survival time by reducing tumor size and eradicating micrometastases [3], current high HCC-associated mortality indicates that the design and synthesis of highly efficient antitumor agents which exert greater efficacy to HCC without obvious toxicity remain of significant importance [4]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
