OSW-1: a Natural Compound With Potent Anticancer Activity and a Novel Mechanism of Action

Abstract

The naturally occurring compound 3beta,16beta,17alpha-trihydroxycholest-5-en-22-one 16-O-(2-O-4-methoxybenzoyl-beta-D-xylopyranosyl)-(1-->3)-(2-O-acetyl-alpha-L-arabinopyranoside) (OSW-1) is found in the bulbs of Ornithogalum saudersiae and is highly cytotoxic against tumor cell lines. Using various human cancer and nonmalignant cell lines, we investigated the anticancer activity and selectivity of OSW-1 and its underlying mechanisms of action. OSW-1 exhibited extremely potent cytotoxic activity against cancer cells in vitro. Nonmalignant cells were statistically significantly less sensitive to OSW-1 than cancer cells, with concentrations that cause a 50% loss of cell viability 40-150-fold greater than those observed in malignant cells. Electron microscopy and biochemical analyses revealed that OSW-1 damaged the mitochondrial membrane and cristae in both human leukemia and pancreatic cancer cells, leading to the loss of transmembrane potential, increase of cytosolic calcium, and activation of calcium-dependent apoptosis. Clones of leukemia cells with mitochondrial DNA defects and respiration deficiency that had adapted the ability to survive in culture without mitochondrial respiration also were resistant to OSW-1. In vitro analysis revealed that OSW-1 effectively killed primary leukemia cells from chronic lymphocytic leukemia patients with disease refractory to fludarabine. The promising anticancer activity of OSW-1 and its unique mechanism of action make this compound worthy of further investigation for its potential to overcome drug resistance.

Effective cytotoxic activity of OSW-1 on colon cancer by inducing apoptosis in vitro and in vivo

“…OSW-1 is a natural compound that has shown considerable anticancer activity in several kinds of cancer cells, including pancreatic cancer, ovarian cancer, leukemia, human hepatomas, and malignant brain tumors (5,39). Herein we showed that OSW-1 can also inhibit colon cancer cells more powerfully than other drugs.…”

“…OSW-1 is classified as cholestane glycoside chemical structure formula: [3β,16β,17α-trihydroxycholest-5-en-22-one16-O-(2-O-4-methoxybenzoyl-β-D-xylopyranosyl)-(1→3)-(2-O-acetyl-α-Larabinopyranoside)]. Several studies have suggested that OSW-1 has a potent anti-proliferative effect against a variety of tumor cell lines, such as leukemia, pancreatic cancer, malignant brain tumor, and hepatocellular carcinoma cells, but is less toxic to non-malignant cells in vitro (5,6); however, it is so difficult to isolate the compound in certain stages that the application is restricted to research. Recent studies have shown that the synthesis of OSW-1 and its derivatives has gradually improved; however, this finding provides the premise for a possible therapeutic application for OSW-1 in the future (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24).…”

Enantioselective Synthesis of (+)-Cephalostatin 1

“…5 Three other molecules, ritterazine B (2), 6 OSW-1 (3) 7 and schweinfurthin A (4) 8 have cytotoxicity patterns resembling 1, suggesting that all three compounds share similar mechanisms. 9 The cellular target and mechanism of 1 (or 2-4) has not been elucidated, although an increasing amount of research is being focused on these issues. 10 The unusually large and complex structure of 1 has been the target of many synthesis studies, with one synthesis reported by Fuchs.…”

Applications of the Single-probe: Mass Spectrometry Imaging and Single Cell Analysis under Ambient Conditions

“…SCMS was also applied to experiments where cells were treated with anticancer drugs ( e.g. , OSW-1, paclitaxel, and doxorubicin) 19 . The corresponding drugs can be detected within HeLa cells after 4-hour treatment at a series of concentrations ( i.e.…”