Marine Anthraquinones: Pharmacological and Toxicological Issues

Abstract

The marine ecosystem, populated by a myriad of animals, plants, and microorganisms, is an inexhaustible reservoir of pharmacologically active molecules. Among the multiple secondary metabolites produced by marine sources, there are anthraquinones and their derivatives. Besides being mainly known to be produced by terrestrial species, even marine organisms and the uncountable kingdom of marine microorganisms biosynthesize anthraquinones. Anthraquinones possess many different biological activities, including a remarkable antitumor activity. However, due to their peculiar chemical structures, anthraquinones are often associated with toxicological issues, even relevant, such as genotoxicity and mutagenicity. The aim of this review is to critically describe the anticancer potential of anthraquinones derived from marine sources and their genotoxic and mutagenic potential. Marine-derived anthraquinones show a promising anticancer potential, although clinical studies are missing. Additionally, an in-depth investigation of their toxicological profile is needed before advocating anthraquinones as a therapeutic armamentarium in the oncological area.

Keywords: anthraquinones; anticancer mechanisms; cytotoxicity; fungi; genotoxicity; in vitro studies; in vivo studies; marine organisms.

Figure 1

Timeline describing all the marine-derived agents approved as anticancer drugs.

Figure 2

Chemical structure of anthraquinones’ (a) and anthracyclines’ core (b).

Figure 3

Chemical structure of emodin.

Figure 4

Chemical structure of physcion.

Figure 5

Chemical structure of aspergiolide A.

Figure 6

Chemical structure of alterporriol A–Y.

Figure 7

Chemical structure of bostrycin.

Figure 8

Chemical structure of nidurufin.

Figure 9

Chemical structure of G503.

Figure 10

Chemical structure of SZ-685C.

Figure 11

Chemical structure of 1403P-3.

Figure 12

Chemical structure of 1’-deoxyrhodoptilometrin and (S)-(−)-rhodoptilometrin.

Figure 13

Chemical structure of tetracenomycin D, heliomycin and tetracenomycin X.

Figure 14

Chemical structure of galvaquinone A–C.

Figure 15

Chemical structure of marmycin A and marmycin B.

Figure 16

Chemical structure of saquayamycin B.

Figure 17

Cellular and molecular mechanisms modulated by AQs. ⊥: inhibition; ↓: decrease; ↑: increase; Akt: protein kinase B; Bax: Bcl-2-associated X protein: Bcl-2: B-cell lymphoma 2; Bcl-xL: B-cell lymphoma-extra large; ER: endoplasmic reticulum; FoxO1: forkhead box O1; FoxO3A: F forkhead box O3A; HDAC: histone deacetylase; ROS: reactive oxygen species; STAT3: signal transducer and activator of transcription 3; p27: cyclin-dependent kinase inhibitor 1B; PARP: poly-(ADP-ribose)-polymerase; PI3K: phosphoinositide 3-kinase; mTOR: mammalian target of rapamycin; ΔΨ: mitochondrial membrane potential.