Oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl protect PC12 pheochromocytoma cells from oxidative stress and apoptosis induced by doxorubicin

Abstract

Background and purpose: Doxorubicin (DOX) as a chemotherapeutic agent has been widely used in the treatment of various types of cancer. However, DOX exerts a toxic effect on normal tissues such as the brain. Furanocoumarins reduce the risk of cardiovascular and brain diseases because of their antioxidant activities. This study has been designed, for the first time, to evaluate the effect of known furanocoumarins oxypeucedanin and isoimperatorin extracted from Prangos ferulacea (L.) Lindl on oxidative stress and apoptosis induced by DOX toward pheochromocytoma cell line (PC12). Experimental approach: NMR and MASS spectrometers were used to characterize the isolated compounds. The protective effects of isolated compounds on DOX-induced cytotoxicity in PC12 cells were examined by MTT assay. PC12 cells were pretreated with oxypeucedanin and isoimperatorin for 2 and 21 h, respectively, subsequently exposure to DOX at IC 50 concentration. Then, mitochondrial membrane potential (MMP), Bax and Bcl2 mRNA expressions, caspase-3 activation, and the generation of intracellular reactive oxygen species (ROS) were measured after 24 h. Findings/Results: Pretreatment with oxypeucedanin and isoimperatorin significantly decreased DOX-induced apoptosis through reduction of caspase-3 activity and ROS generation and an increase in MMP. In addition, our finding showed pretreatment with these compounds leads to regulation of Bcl-2. Conclusion and implications: Taken together our observation indicated that oxypeucedanin and isoimperatorin have a protective effect against apoptosis induced by DOX in PC12 cells by inhibition of ROS production.

INVESTIGATION OF CYTOTOXIC AND APOPTOTIC EFFECTS OF PRANGOS HEYNIAE H. DUMAN & M. F. WATSON EXTRACTS ON HEPG2 CELLS

“…Previous studies suggested that OXY, OST, and ISO led to anticancer activities and induced apoptosis by activating caspase-3, -8, and -9 proteins in various types of human cancer cells, including DU145 [33], CD133 [34], PC-3, H1299 [35]. In contrast, one study revealed that OXY and ISO decrease caspase-3 activity, increase MMP, and demonstrate a protective effect against doxorubicin-induced apoptosis and neurotoxicity in PC-12 cells [36]. As seen in Fig.…”

Oksipösedanin kaynaklı antikanser aktivitenin in siliko ve in vitro değerlendirilmesi: Mitotoksisite?

“…3,4 OXY was reported to have anti-mutagenic, cytotoxic, and antiproliferative activities against several cancer cells, including colon, breast, liver, and lung cancers. [5][6][7] Cancer cells need more significant biosynthetic components and building blocks, including amino acids and nucleotides, than normal cells due to their uncontrolled and highly proliferative cell division characteristics. Also, the expression of proapoptotic proteins is lower in cancer cells than in normal cells, which makes cancer cells more resistant to anti-cancer treatments and molecules.…”