The Use of Naphthoquinones and Furano-naphthoquinones as Antiinvasive Agents

Abstract

Cancer is a leading cause of mortality in the world and metastasis is to blame. Invasion is the initial step of metastasis. Therapies targeting epithelial-mesenchymal transition (EMT), cancer stem cells (CSCs) and signal transducer and activator of transcription 3 (STAT3) signaling pathways can reduce stemness of cancer cells and thus inhibit cancer invasion. A large number of anti-cancer naphthoquinones (NQs) can target cancer invasion by acting on EMT, CSCs and STAT3 signaling. Furano-naphthoquinones (FNQs) belong to a class of NQ derivatives commonly characterized by a naphthoquinone fused with a furano ring. A study indicated that the corporation of the furano ring improved the anticancer potency as compared to the other classes of NQs. BBI608, a natural FNQ, which can be found in the woods or barks of several Tabebuia species, has entered phases I and II clinical trials. It has been regarded as a potential candidate for new-generation lead compound acting directly on CSCs to overcome the chemotherapy resistance. Apart from the natural plant sources, there are a number of synthetic FNQ derivatives that are effective in reducing stemness of cancer cells and thus are anti-invasive. In this review, the anti-invasion mechanisms of NQs and the more powerful FNQs, together with their natural origins, synthetic derivatives as well as their synthetic routes are discussed.

Ventilagolin Suppresses Migration, Invasion and Epithelial-Mesenchymal Transition of Hepatocellular Carcinoma Cells by Downregulating Pim-1

“…24,25 In the family of quinones, 1.4-naphthoquinones are the most important, as their derivatives exhibit a wide variety of biological properties, 26 and some of them (eg, shikonin, plumbagin) have been found to act against invasion and metastasis in a variety of cancers, such as leukemia, breast, colon and lung cancers. 27 In this study, we demonstrated the effects of a natural 1.4-naphthoquinone derivative Ventilagolin on migration, invasion and EMT of human HCC and determined the possible underlying mechanism. We showed that Ventilagolin inhibited the proliferation of HepG2 and SMMC-7721 cells and suppressed HCC tumor growth of nude mice in a dose-dependent manner.…”

“… 24 , 25 In the family of quinones, 1.4-naphthoquinones are the most important, as their derivatives exhibit a wide variety of biological properties, 26 and some of them (eg, shikonin, plumbagin) have been found to act against invasion and metastasis in a variety of cancers, such as leukemia, breast, colon and lung cancers. 27 …”

Synthetic Naphthofuranquinone Derivatives Are Effective in Eliminating Drug-Resistant Candida albicans in Hyphal, Biofilm, and Intracellular Forms: An Application for Skin-Infection Treatment

“…There are only four classes of USFDA-approved antifungal drugs to treat candidiasis, including the structures of flucytosines, azoles, echinocandins, and polyenes. Naphthofuranquinones are a quinine subclass possessing some bioactivities such as antimicrobial, anti-inflammatory, and antitumor potencies (Tsang et al, 2018). Previous studies (Gershon and Shanks, 1975;Nagata et al, 1998;Neto et al, 2014;Rejiniemon et al, 2014;Hassan et al, 2016;Xie et al, 2016) demonstrated that naphthofuranquinones showed the capability to eradicate Candida species.…”

Avaliação da atividade antiproliferativa de extratos hidroalcoólicos de plantas em linhagens celulares humanas de câncer de mama, fígado e próstata

“…Seus efeitos em linhagens celulares de câncer são bastante citados na literatura e, corroborando com nossos estudos, de forma geral apresentam atividade em diversos tipos de câncer como: mama, endométrio, ovário, próstata, cólon, pulmão, pâncreas, esôfago, bexiga, linfoma, fígado (CHANG et al, 2003;DEEP et al, 2016;KIM et al, 1998;LIAW et al, 2002;LIU et al, 2016;QAZI et al, 2018;RIESER et al, 1996;SUN et al, 2014;TORRES et al, 2012;YANG;LEE, 2016;YAP et al, 2017). furano-naftoquinonas, com maior destaque para o lapachol e a β-lapachona (LEE et al, 2015;TSANG et al, 2017). Estudos de citotoxicidade em linhagens de câncer mostraram pouco ou nenhum efeito em relação aos efeitos de extratos de malva.…”