Selective cytotoxic activity of the marine-derived batzelline compounds against pancreatic cancer cell lines

Abstract

Pancreatic cancer is the fourth leading cause of cancer death in the United States. The prognosis of the disease is very negative since the cancer has usually metastasized by the time a patient manifests symptoms. Although combination therapy shows some promise, new drugs to treat the disease are needed. Given our interest in finding new therapies for pancreatic cancer, we sought to determine whether the known cytotoxic activity of the batzellines extended to pancreatic cancer cell lines. The batzellines are pyrroloiminoquinones alkaloids obtained from the deep water Caribbean sponge Batzella sp (family Esperiopsidae, order Poecilosclerida). We show here that batzellines exhibit selective cytotoxicity towards the pancreatic cancer cell lines AsPC-1, Panc-1, BxPC-3, and MIA PaCa2 compared to the normal African green monkey cell line Vero. The batzellines cause cytotoxicity by inducing cell cycle arrest that is mediated by their ability to intercalate into DNA and/or inhibit Topoisomerase II activity. The cytotoxic abilities of Isobatzellines A and C against pancreatic cancer cell lines, their low toxicity against normal cells and their reported ability to be synthesized makes them interesting compounds with potential chemotherapeutic effects that may merit further research.

Structure elucidation of the new citharoxazole from the Mediterranean deep‐sea sponge Latrunculia (Biannulata) citharistae

“…Indeed, one quaternary carbon was not observed in the 13 C NMR spectrum probably because of slow spin relaxation, which thus required HMBC data for its assignment. A first HMBC experiment optimized for 5 Hz (500 MHz) was performed.…”

“…Importantly we noticed that for all reported examples, 3 J H1 CNC values always range between 8.2 and 10.7 Hz, whereas 3 J H1 COC are smaller with values between 3.5 and 5.6 Hz. [17] Instead of running non decoupled 13 C carbon experiments which would have been difficult to interpret, we used the relation between the intensity of the HMBC correlation and the J HC corresponding value in order to assess the 3 J H1 CXC coupling constant values of 1. Using standard mathematical equations linking the intensity of the HMBC correlation with 3 J CH , the 3 J H1 COC theoretical intensity will always be higher than the 3 J H1 CNC intensity with a mixing time of τ = 125 ms (4 Hz optimized HMBC experiment), the intensity ratio being inverted with τ = 250 ms (2 Hz optimized HMBC experiment) (Fig.…”

“…[11,12] Interesting cytotoxic activities are associated with some of these aromatic alkaloids. [13] In the Mediterranean sea, only one species of the Latrunculia genus has been described. Latrunculia (Biannulata) citharistae Vacelet, 1969, was found at depths around 130-150 m in the western Mediterranean sea, [14] and no chemical study has been reported for this species so far.…”

Spongiatriol Inhibits Nuclear Factor Kappa B Activation and Induces Apoptosis in Pancreatic Cancer Cells

“…Discalamide A is related to these compounds and to the theopederins, the latter of which have also been reported to inhibit protein synthesis [13]. Isobatzelline C intercalates into DNA and secobatzelline A inhibits topoisomerase II activity [14]; both of these activities would lead to transcriptional inhibition. Therefore, of the actives from the primary assay, spongiatriol and discorhabdin A may show specific inhibition of NFκB and warrant further investigation.…”

Anticancer Drugs Discovery and Development from Marine Organisms

“…The batzellines cause cytotoxicity by inducing cell cycle arrest that is mediated by their ability to intercalate into DNA and/or inhibit topoisomerase II activity. The cytotoxic abilities of isobatzellines A and C against pancreatic cancer cell lines, their low toxicity against normal cells, and their reported ability to be synthesized makes them interesting compounds with potential chemotherapeutic effects that may merit further research [50]. Sipholenol A, a sipholane triterpene isolated from the Red Sea sponge, Callyspongia siphonella, potently reversed multidrug resistance (MDR) in cancer cells that overexpressed P-glycoprotein (P-gp).…”