| Description: |
Isoalantolactone, an apoptosis inducer, possesses multiple biological activities including antifungal, anthelmintic, antimicrobial, anti-inflammatory, antitrypanosomal activities and antiproliferative effects on several cancer cell lines, such as colon, melanoma, ovary, prostate, lung, and leukemia. Isoalantolactone induces apoptosis, may be mediated through caspase-dependent apoptotic pathways, S phase arrest, inhibition of phosphorylation of PI3K/Akt, and downregulation of Bcr/Abl. |
| Targets: |
Bcr-Abl | PI3K | Akt | PARP | Caspase | ROS | MMP(e.g.TIMP) | NF-kB | p65 | Bcl-2/Bax | p38MAPK |
| In vitro: |
| Phytother Res. 2014 Nov;28(11):1679-86. | | Growth inhibition effects of isoalantolactone on K562/A02 cells: caspase-dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl.[Pubmed: 24865355] | Isoalantolactone, a sesquiterpene lactone, is the active component of Inula helenium (Compositae). It has been reported that isoalantolactone has the capacity to inhibit tumor cell growth through induction of apoptosis. The purposes of this study were to evaluate the effects of isoalantolactone on the human erythroleukemia drug-resistant cell line K562/A02 and to provide evidence of its function as a potent therapeutic agent in patients with chronic myelogenous leukemia with the Bcr/Abl phenotype.
METHODS AND RESULTS:
Our results showed that isoalantolactone significantly inhibited K562/A02 cell growth by downregulating Bcr/Abl expression. Isoalantolactone also induced apoptosis via increase generation of reactive oxygen species, modulation of the protein levels of Bcl-2 family members, caspase activation, poly ADP-ribose polymerase (PARP) cleavage, and release of cytochrome c. We also observed that isoalantolactone inhibited proliferation by inducing cell cycle arrest in the S phase.
CONCLUSIONS:
Taken together, all these findings support that growth inhibition effects of isoalantolactone on K562/A02 cells may be mediated through caspase-dependent apoptotic pathways, S phase arrest, and downregulation of Bcr/Abl. | | Crop Prot., 2006, 25(5):508-11. | | Repellent, insecticidal and phytotoxic activities of isoalantolactone from Inula racemosa.[Reference: WebLink] | Isoalantolactone, a natural product isolated from traditional Chinese medicinal herb roots of Inula racemosa Hook. f. (Fam. Compositae), has been shown to possess strong antifungal activities.
METHODS AND RESULTS:
The present investigation showed that isoalantolactone also exhibited repellent and toxic activities against rice weevil [Sitophilus oryzae (L.) (Coleoptera: Curculionidae)] based on a food preference apparatus and a poisoned food technique. The toxicity of isoalantolactone to rice weevil was dose dependent, whereas the repellency was not. Isoalantolactone showed strong phytotoxic effects on seed germination and seedling growth of wheat at a concentration of 500 μg ml−1 for 60 h; however, this side effect could be reduced markedly by shortening the treating time at this concentration.
CONCLUSIONS:
Results indicate that isoalantolactone might be considered for wheat seeds preservation in control of storage weevils. |
|
| In vivo: |
| Int J Biol Sci. 2012;8(4):533-47. | | Isoalantolactone induces reactive oxygen species mediated apoptosis in pancreatic carcinoma PANC-1 cells.[Pubmed: 22532787 ] | Isoalantolactone, a sesquiterpene lactone compound possesses antifungal, antibacteria, antihelminthic and antiproliferative activities.
METHODS AND RESULTS:
In the present study, we found that Isoalantolactone inhibits growth and induces apoptosis in pancreatic cancer cells. Further mechanistic studies revealed that induction of apoptosis is associated with increased generation of reactive oxygen species, cardiolipin oxidation, reduced mitochondrial membrane potential, release of cytochrome c and cell cycle arrest at S phase. N-Acetyl Cysteine (NAC), a specific ROS inhibitor restored cell viability and completely blocked Isoalantolactone-mediated apoptosis in PANC-1 cells indicating that ROS are involved in Isoalantolactone-mediated apoptosis. Western blot study showed that Isoalantolactone increased the expression of phosphorylated p38 MAPK, Bax, and cleaved caspase-3 and decreased the expression of Bcl-2 in a dose-dependent manner. No change in expression of phosphorylated p38 MAPK and Bax was found when cells were treated with Isoalantolactone in the presence of NAC, indicating that activation of these proteins is directly dependent on ROS generation.
CONCLUSIONS:
The present study provides evidence for the first time that Isoalantolactone induces ROS-dependent apoptosis through intrinsic pathway. Furthermore, our in vivo toxicity study demonstrated that Isoalantolactone did not induce any acute or chronic toxicity in liver and kidneys of CD1 mice at dose of 100 mg/kg body weight. Therefore, Isoalantolactone may be a safe chemotherapeutic candidate for the treatment of human pancreatic carcinoma. |
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