Kahalalide F preferentially induces cell death via oncosis in tumor cells

(Breast and Prostate Cancer-February 5, 2004)

According to a study from Spain, "Kahalalide F is a novel antitumor drug of marine origin under clinical investigation that showed a potent cytotoxic activity against a panel of human prostate and breast cancer cell lines, with IC50 ranging from 0.07 microm (PC3) to 0.28 microm (DU145, LNCaP, SKBR-3, BT474, MCF7).

"Importantly, nontumor human cells (MCF10A, HUVEC, HMEC-1, IMR90) were 5-40 times less sensitive to the drug (IC50 = 1.6-3.1 micro M). KF cytotoxicity did not correlate with the expression level of the multidrug resistance MDR1 and of the tyrosine kinase HER2/NEU, and only slightly by the antiapoptotic BCL-2 protein," wrote Y. Suarez and colleagues, University of Autonoma Madrid, CSIC.

"KF action was triggered rapidly by short pulse treatments (15 min caused 50% maximum cytotoxicity). Neither a general caspase inhibitor (Z-VAD-fmk) nor transcription or translation inhibitors (actinomycin D, cycloheximide) blocked KF action. Flow cytometry analysis revealed that KF induced neither cell-cycle arrest nor apoptotic hypodiploid peak. Using mitochondrial (JC-1)- and lysosomal (LysoTracker Green, Acridine Orange)-specific fluorophores, we detected loss of mitochondrial membrane potential and of lysosomal integrity following KF treatment," the researchers wrote.

"Confocal laser and electron microscopy revealed that KF-treated cells underwent a series of profound alterations including severe cytoplasmic swelling and vacuolization, dilation, and vesiculation of the endoplasmic reticulum, mitochondrial damage, and plasma membrane rupture," they added.

The researchers concluded: "In contrast, the cell nucleus showed irregular clumping of chromatin into small, condensed masses, while chromatin disappeared from other nuclear domains, but the nuclear envelope was preserved and no DNA degradation was detected. Together, these data indicate that KF induces cell death via oncosis preferentially in tumor cells."

Suarez and colleagues published the results of their research in Molecular Cancer Therapeutics (Kahalalide F, a new marine-derived compound, induces oncosis in human prostate and breast cancer cells. Mol Cancer Ther, 2003;2(9):863-872).

The information in this article comes under the major subject areas of Urology and Oncology. This article was prepared by Women's Health Weekly editors from staff and other reports.

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