Catha edulis (Khat) Induces Cell Death by Apoptosis in Leukemia Cell Lines

Abstract

Khat is the Celastraceus edulis plant, a flowering evergreen tree or large shrub, which grows in the Horn of Africa and southwestern Arabia. Khat use has been associated with development of oral cancer, but its molecular effects remain controversial. This study describes a novel cytotoxic effect of whole khat extract on three leukemia cell lines. Cells were exposed to khat extract and harvested for analysis by fluorescent and electron microscopy, trypan blue exclusion, as well as immunoblotting to characterize the mode of cell death. In a separate series, cells were pretreated with a panel of caspase inhibitors for possible inhibitory effects. Khat induced a rapid cell death effect in HL-60, Jurkat, and NB4 cells that occurred within 2 h of exposure. The treated cells retained their ability to exclude trypan blue dye, a key feature in the apoptotic process. Exposed cells consistently developed morphological features of manifest apoptosis. Z-VAD, a pan-caspase inhibitor, completely inhibited toxic activity for up to 8 h, with partial inhibition by other caspase-specific agents. Western blot analysis showed specific cleavage of caspase-3 in khat-exposed cells. This study shows that khat induces cell death by apoptosis in a process sensitive to inhibition by caspase inhibitors, suggesting that subcellular interactions could be of particular relevance for the biological effects of khat in the cell death process and possibly carcinogenesis.

Anti-inflammatory, pro-apoptotic, and anti-proliferative effects of a methanolic neem (Azadirachta indica) leaf extract are mediated via modulation of the nuclear factor-κB pathway

“…[51], Arnebia nobilis [64], Cimicifuga foetida [65], Brassica oleracea [35], Calendula officinalis [25], Pereskia bleo (Kunth) DC. (Cactaceae) [61], and Catha edulis (Khat) [16].…”

The burden of oral cancer in sub-Saharan Africa

“…32,33 Potentially malignant white lesions such as Khat-induced leukoplakia have been described in chewers with higher prevalence among those who simultaneously consume tobacco 34 and alcohol. [35][36][37] A large part of the Indian ethnic population in Africa (Kenya, South Africa in particular) still consume areca nut, commonly embedded in betel quid containing shredded tobacco, scented products and slaked lime (Paan masala). It was reported in 1993 that the areca nut is chewed alone by 93% of Indian women in South Africa.…”

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

“…In rats, a decreased serum level of free radical metabolising/ scavenging enzymes and glucose has been observed after oral administration, suggesting a deranged systemic capacity to handle oxidative radicals after khat use (Al-Qirim et al, 2002). It has also been reported that khat induces cytotoxic effects in cells (Al-Ahdal et al, 1988;Al-Meshal et al, 1991;Al-Mamary et al, 2002;Dimba et al, 2003) and in lymphoid tissue, and in the liver and kidney after per oral administration to white rabbits (Al-Meshal et al, 1991;Al-Mamary et al, 2002), but the mode of cell death has not so far been addressed.…”