Crude alkaloid extract of Rhazya stricta inhibits cell growth and sensitizes human lung cancer cells to cisplatin through induction of apoptosis

Abstract

There is an urgent need to improve the clinical management of non-small cell lung cancer (NSCLC), one of the most frequent causes of cancer-related deaths in men and women worldwide. Rhazya stricta, an important medicinal plant used in traditional Oriental medicine, possesses anti-oxidant, anti-carcinogenic and free radical scavenging properties. This study was done to explore the potential anticancer activity of a crude alkaloid extract of R. stricta (CAERS) against the NSCLC line A549. CAERS markedly suppressed the growth of A549 cells and considerably enhanced the anti-proliferative potential of cisplatin. CAERS-mediated inhibition of A549 cell growth correlated with the induction of apoptosis that was accompanied by numerous morphological changes, DNA fragmentation, an increase in the Bax/Bcl-2 ratio, the release of mitochondrial cytochrome c, activation of caspases 3 and 9 and cleavage of poly(ADP-ribose)-polymerase. CAERS reduced the constitutive expression of anti-apoptotic proteins (Bcl-2, Bcl-XL, Mcl-1 and Survivin) and cell cycle regulating proteins (cyclin D1 and c-Myc), but enhanced expression of the proapoptotic proteins Noxa and BAD. These observations indicate that CAERS induced apoptosis and sensitized NSCLC to cisplatin via a mitochondria-mediated apoptotic pathway. These data provide a rationale for using a combination of CAERS and CDDP to treat NSCLC and other CDDP-resistant tumors.

Biochemical and histological evidences for the antitumor potential of <i>Teucrium Oliverianum</i> and <i>Rhazya stricta</i> in chemically-induced hepatocellular carcinoma

“…This may be attributed to indole alkaloids in R. stricta which have been found to possess numerous biological activities and anticancer potentiality (Gilani et al, 2007). It has been found that a crude alkaloid extract from R. stricta inhibited cell growth and sensitized human lung cancer cells, A549, to cisplatin through induction of apoptosis (Elkady, 2013). Photomicrograph of liver tissue section of rat in HCC group showed hepatic parenchyma with foci of anaplastic hepatocellular carcinoma as well as other foci of cystic cholangio carcinoma associated with areas of telangictasis with haemorrhage as well as individual hepatocellular necrosis (Fig.…”

“…This may be the underlying mechanism for the reduction of these tumor markers by R. stricta extract supplementation. Also, it has been found that a crude alkaloid extract from R. stricta inhibited cell growth and sensitized human lung cancer cells, A549, to cisplatin through induction of apoptosis (Elkady, 2013).…”

Antibacterial activities of Rhazya stricta leaf extracts against multidrug-resistant human pathogens

“…[24] Briefly, fresh R. stricta leaves were washed and dried under shade. Dried leaves (350 g) were soaked in 80% ethanol for three days and then filtered and evaporated using a rotary evaporator (Buchi, Switzerland).…”

“…An equal volume of chloroform was added, and the solution was shaken for 3 h. Finally, two layers were formed, one the chloroform layer, from which alkaloids were extracted, and the other the aqueous layer, from which non-alkaloids were extracted; the separate contents of both layers were immediately freeze-dried. [24] Preparation of whole aqueous extract from R. stricta leaves WAE was prepared according to our laboratory protocol as described by Kabli et al [23] In brief, washed fresh leaves of R. stricta were cut into small pieces and 96 g were taken along with 1 L of distilled water in a blender The mixture was left for 24 h in a shaker at room temperature. The mixture was later filtered with filter paper (125 mm), and then with membrane filters (0.22 mm).…”

The aqueous extract of cinnamon bark ameliorated cisplatin-induced cytotoxicity in vero cells without compromising the anticancer efficiency of cisplatin

“…For rNa extraction and reverse transcriptase-pcr, gene-specific primers were used as previously described 26,27 .…”