Table 1.

Marine derived compounds with TRAIL-overcoming resistance activity and/or able to regulate TRAIL signaling components or inhibitors.

Chemical Class	Drug	Marine Source	Target Cell Line	Effects	Restores or Enhances TRAIL-Induced Apoptosis
Alkaloid	Manzamine A	Marine Sponge	AsPC-1 [180]	Inhibition of GSK3β and NF-κB	Yes
	Trabectedin	Marine Tunicate	MCF-7 & MDA-MB-453 [181]	Up-regulation of DR4, DR5, FADD, Bax, Bad Down-regulation of Bcl-2, Bcl-xL, XIAP and survivin	Yes
	Aplidin	Marine Tunicate	Multiple Myeloma cell lines and tumors [179]	Activation of p38 and JNK MAPK Down regulation of Mcl-1, Survivin Up-regulation of TRAIL	Not Tested
Aureolic acid	Chromomycins A2 Chromomycins A3	Actinomycetes	AGS [182]	Inhibition of wnt/β-catenin	Yes
Carotenoids	Halocynthiaxanthin	Oysters and Sea Squirts	DLD-1 [183]	Up-regulation of DR5	Yes
	Peridinin	Squirt Botrylloides	DLD-1 [183]	Up-regulation of DR5	Yes
	Siphonaxanthin	Green Algae	HL-60 [184]	Up-regulation of DR5 Down-regulation of Bcl-2	Not Tested
Macroloactones	Pectenotoxin-2	Marine Sponge	Hep3B & HepG2 [185]	Up-regulation of DR4, DR5, and Bax. Down-regulation of Bcl-2 and Bcl-xL	Not Tested
Sesquiterpene	Aplysin	Seaweed	MCF-7 [122]	Inhibition of p38 MAPK/ survivin pathway.	Yes
	Ilimaquinone	Marine Sponge	HCT116 & HT29 [126]	Up-regulation of DR4 and DR5 through ERK/p38 and CHOP	Yes
Sphingosine	Sphingoid bases	Sea Cucumber	HepG2 [186]	Up-regulation DR5 and Bax, Down-regulation of Akt/(PKB).	Not Tested