Growth Inhibition of Various Human Cancer Cell Lines by Imperatorin and Limonin from Poncirus Trifoliata Rafin. Seeds

Abstract

We examined the anticancer effects of limonin and imperatorin on various human cancer cells by MTT assay, and the results showed that imperatorin inhibited the cell growth of SNU 449 (liver cancer) and HCT-15 (colon cancer) cells in a dose-dependent manner, while limonin had less effect. Exposure of different concentrations of limonin and imperatorin caused morphological changes in cancer cells, but not in normal dermal fibroblast cells. Limonin and imperatorin induced apoptotic cell death concurrent to cell cycle arrest in SNU 449 and HCT-15 cells. Limonin and imperatorin up regulated proapoptotic protein Bax expression and down regulated anti-apoptotic protein Bcl-2 expression in a dose-dependent manner in HCT-15 and SNU 449 cells. In conclusion, our data demonstrate that limonin and imperatorin have anticancer potential which is associated with promoting cell apoptosis through expression of apoptosis-related proteins.

Anticancer effect of Limonin against benzo(a)pyrene‐induced lung carcinogenesis in Swiss albino mice and the inhibition of A549 cell proliferation through apoptotic pathway

“…Thus, the growth inhibitory potential of limonin against A549 cells certainly resulted, at least, in part, from its capability to enhance apoptosis. Previous studies suggested that the anticancer effect of limonin was studied in various cancer cell lines, such as HCT‐15 (colon cancer) and SNU 449 (liver cancer) . The morphological changes of cancer cells, including chromatin condensation, nuclear fragmentation, and cellular shrinkage were observed, whereas cells treated with limonin altered the morphological changes in the cancer cells.…”

“…Limonin is a dietary phytochemical, which has been reported in many biological activities such as insect antifeedant, insecticidal, antimalarial, hepatoprotective, the growth‐regulating activity of insects, antiviral, antilipidemic, and antioxidant . Limonin displaying the anticancer effects in vitro and suppressive properties of the development of preneoplastic lesions in vivo has been reported . The intention of our present examination is the anticancer effects of limonin on lung cancer induced by B(a)P in Swiss albino mice and A549 lung cancer cell lines.…”

Imperatorin acts as a cisplatin sensitizer via downregulating Mcl-1 expression in HCC chemotherapy

“…Imperatorin, a linear furanocoumarin compound, is the major active ingredientis isolated from the root of Angelica dahurica which is the traditional Chinese medicine [8]. The reported pharmacological activities of imperatorin include analgesic, anti-inflammatory, anti-coagulant, and inhibition of myocardial hypertrophy [9,10].…”

Phytotherapeutic effects of the fruits of Poncirus trifoliata (L.) Raf. on cancer, inflammation, and digestive dysfunction

“…Neohesperidin, a flavonoid abundant in MF, also induces apoptotic cell death through the activation of proapoptotic regulators, namely, B‐cell lymphoma 2 and B‐cell lymphoma 2‐associated X protein, in breast adenocarcinoma (MDA‐MB‐231) cells (F. Xu et al, ). Similarly, limonin and imperatorin isolated from the seeds of MF, up‐regulate the expression of B‐cell lymphoma 2‐associated X protein, and suppress the growth of liver (SNU 449) and colon cancer (HCT‐15) cells (Rahman, Siddiqui, Jakhar, & Kang, ). In addition, β‐sitosterol and 2‐hydroxy‐1,2,3‐propanetricarboxylic acid 2‐methyl ester isolated from the acetone extract of MF inhibit proliferation of human colon cancer (HT‐29) cells, without exhibiting any cytostatic effects on noncancerous fibroblast (COS‐1) cells (Jayaprakasha et al, ).…”