8-methoxypsoralen reduces AKT phosphorylation, induces intrinsic and extrinsic apoptotic pathways, and suppresses cell growth of SK-N-AS neuroblastoma and SW620 metastatic colon cancer cells.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE:

8-methoxypsoralen (8-MOP) is a furanocoumarin and an active compound of a traditional Egyptian medicinal plant Ammi majus L, whose juice/fruit has been used for many years in folk phototherapy for the treatment of vitiligo or a hyperproliferative skin disorder, psoriasis. 8-MOP together with UVA light is also used as an anticancer drug for the treatment of cutaneous T-cell lymphoma. However, furanocoumarins exert anticancer activity even without UV irradiation.

AIM OF THE STUDY:

Evaluation UV-independent anticancer activity of 8-MOP in human cancer cell lines and identification of the mechanisms involved in this action. Results could provide new data about a potential role of 8-MOP in prevention and growth suppression in a broad spectrum of cancers.

MATERIALS AND METHODS:

8-MOP (99%, HPLC/MS assay) was isolated from A. majus fruits by chromatographic methods. The effect of 8-MOP on cell viability was evaluated by the MTT test in several human cancer cell lines. Anti-proliferative activity of 8-MOP was evaluated by the BrdU assay in neuroblastoma (SK-N-AS) and metastatic colon cancer (SW620) cells. The Hoechst/PI staining was used for morphological analysis of cell death. An annexin V-FITC/PI double labelling and Cell Death Detection ELISA kit were used to detect apoptosis. The expression of apoptosis-associated proteins and the AKT activation status were determined by Western blot analysis.

RESULTS:

8-MOP inhibited cell growth in several cancer cell lines. The SK-N-AS and SW620 cells were the most sensitive to the compound. 8-MOP reduced the phosphorylation of AKT308, decreased the expression of Bcl-2, increased the Bax protein level, and activated caspases -8, -9, and -3 in both cell lines.

CONCLUSIONS:

8-MOP impairs the PI3K/AKT signalling pathway and, independently of photoactivation, can inhibit the growth of neuroblastoma and colon cancer cells by induction of apoptosis via intrinsic and extrinsic pathways.

• Authors: Magdalena Bartnik, Adrianna Sławińska-Brych, Aleksandra Żurek, Martyna Kandefer-Szerszeń, Barbara Zdzisińska
• Journal: Journal of ethnopharmacology (J Ethnopharmacol) Vol. 207 Pg. 19-29 (Jul 31 2017) ISSN: 1872-7573 [Electronic] Ireland
• PMID: 28627461 (Publication Type: Journal Article)
• Copyright: Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents, Phytogenic
• Proto-Oncogene Proteins c-akt
• Methoxsalen

Topics

• Ammi (chemistry)
• Antineoplastic Agents, Phytogenic (isolation & purification, pharmacology)
• Apoptosis (drug effects)
• Cell Line, Tumor
• Cell Survival (drug effects)
• Chromatography, High Pressure Liquid (methods)
• Colonic Neoplasms (drug therapy, pathology)
• Egypt
• Enzyme-Linked Immunosorbent Assay
• Fruit
• Humans
• Mass Spectrometry (methods)
• Methoxsalen (isolation & purification, pharmacology)
• Neuroblastoma (drug therapy, pathology)
• Phosphorylation
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)