Abstract

Breast cancer is a global health problem being the most common and the leading cause of cancer death among women, which mandates the development of novel strategies for its treatment and prevention. Rhazya stricta Decne (Harmal) is an important medicinal plant used in traditional oriental medicine. It has anti-oxidant, anti-carcinogenic, and free radical scavenging properties. Our purpose was to confirm the potential anticancer activity of Harmal against human breast cancer cells in vitro and to elucidate the mechanism of its activity. We found that ethanol extract of Harmalpotently inhibited cellular growth and colony formation of human breast cancer cell lines, MCF-7 and MDA-MB-231, in a dose- and time-dependent manner. Furthermore, it induced sequences of events marked by apoptosis, accompanied by a loss of cell viability, chromatin condensation, DNA fragmentation and proteolytic cleavage of poly (ADP-ribose) polymerase. Harmal-dependent apoptotic mechanisms involved an increase in the Bax/Bcl-2 ratio and down-regulation of all c-myc, human telomerase reverse transcriptase, and cyclin D1 proteins. From these results, we conclude that Harmal exerts antiproliferative action on breast cancer cells through apoptosis induction, and that it may be a potentially effective chemopreventive or therapeutic agent against breast cancer.

Key words: Chemoprevention, medicinal plants, breast cancers, apoptosis, cell cycle.

Abbreviation

PARP, Poly (ADP-ribose) polymerase; hTERT, human telomerase reverse transcriptase; RT-PCR, reverse transcription-polymerase chain reaction;HPRT1, hypoxanthine-guanine phosphoribosyl transferase; IC₅₀, 50% inhibitoryconcentration.