Costunolide Induces G1/S Phase Arrest and Activates Mitochondrial-mediated Apoptotic Pathways in SK-MES 1 Human Lung Squamous Carcinoma Cells

Overview

Journal Oncol Lett

Specialty Oncology

Date 2016 Apr 14

PMID 27073552

Citations 19

Authors

Peiyan Hua

Guangxin Zhang

Yifan Zhang

Mei Sun

Ranji Cui

Xin Li

Bingjin Li

Xingyi Zhang

Affiliations

Soon will be listed here.

Abstract

Despite the availability of several therapeutic options, a safer and more effective modality strategy is required for the treatment of lung cancer. Costunolide, a sesquiterpene lactone which isolated from the Saussurea lappa, has potent anticancer properties. In the present study, the effects of costunolide on cell viability, the cell cycle and apoptosis in SK-MES-1 human lung squamous carcinoma cells were investigated. Costunolide induced morphological changes and inhibited growth of SK-MES-1 cells growth. Flow cytometric analysis data demonstrated that costunolide significantly induced apoptosis of SK-MES-1 cells and induced cell cycle arrest at G1/S phase in a dose-dependent manner. Through upregulation in the expression of p53 and Bax, and downregulation in the expression of Bcl-2 and activation of caspase-3, costunolide-induced apoptosis was confirmed by western blot analysis. In addition, the significant loss of mitochondrial membrane potential indicated that costunolide may induce apoptosis via the mitochondria-dependent pathway in SK-MES-1 cells. These results highlight the potential effects of costunolide as an anti-cancer agent in a human lung squamous carcinoma cell line.

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References

Choi S, Im E, Kang H, Lee J, Kwak H, Bae Y . Inhibitory effects of costunolide on the telomerase activity in human breast carcinoma cells. Cancer Lett. 2005; 227(2):153-62. DOI: 10.1016/j.canlet.2005.01.011. View

Kretschmer N, Rinner B, Stuendl N, Kaltenegger H, Wolf E, Kunert O . Effect of costunolide and dehydrocostus lactone on cell cycle, apoptosis, and ABC transporter expression in human soft tissue sarcoma cells. Planta Med. 2012; 78(16):1749-56. DOI: 10.1055/s-0032-1315385. View

Ly J, Grubb D, Lawen A . The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis. 2003; 8(2):115-28. DOI: 10.1023/a:1022945107762. View

Saba N, Khuri F . Chemoprevention strategies for patients with lung cancer in the context of screening. Clin Lung Cancer. 2005; 7(2):92-9. DOI: 10.3816/CLC.2005.n.023. View

Hibasami H, Yamada Y, Moteki H, Katsuzaki H, Imai K, Yoshioka K . Sesquiterpenes (costunolide and zaluzanin D) isolated from laurel (Laurus nobilis L.) induce cell death and morphological change indicative of apoptotic chromatin condensation in leukemia HL-60 cells. Int J Mol Med. 2003; 12(2):147-51. View

Chou J, Lai S, Pan S, Jow G, Chern J, Guh J . Investigation of anticancer mechanism of thiadiazole-based compound in human non-small cell lung cancer A549 cells. Biochem Pharmacol. 2003; 66(1):115-24. DOI: 10.1016/s0006-2952(03)00254-5. View

Wedge D, Galindo J, Macias F . Fungicidal activity of natural and synthetic sesquiterpene lactone analogs. Phytochemistry. 2000; 53(7):747-57. DOI: 10.1016/s0031-9422(00)00008-x. View

Yang Y, Kim J, Lee K, Choi J . Costunolide induces apoptosis in platinum-resistant human ovarian cancer cells by generating reactive oxygen species. Gynecol Oncol. 2011; 123(3):588-96. DOI: 10.1016/j.ygyno.2011.08.031. View

Hsu J, Pan S, Ho Y, Hwang T, Kung F, Guh J . Costunolide induces apoptosis through nuclear calcium2+ overload and DNA damage response in human prostate cancer. J Urol. 2011; 185(5):1967-74. DOI: 10.1016/j.juro.2010.12.091. View

10.

Sakuragi N, Salah-Eldin A, Watari H, Itoh T, Inoue S, Moriuchi T . Bax, Bcl-2, and p53 expression in endometrial cancer. Gynecol Oncol. 2002; 86(3):288-96. DOI: 10.1006/gyno.2002.6742. View

11.

Gu J, Gills J, Park E, Mata-Greenwood E, Hawthorne M, Axelrod F . Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity. J Nat Prod. 2002; 65(4):532-6. DOI: 10.1021/np010545m. View

12.

Choi J, Lee K . Costunolide-induced apoptosis in human leukemia cells: involvement of c-jun N-terminal kinase activation. Biol Pharm Bull. 2009; 32(10):1803-8. DOI: 10.1248/bpb.32.1803. View

13.

Komiya T, Yamada Y, Moteki H, Katsuzaki H, Imai K, Hibasami H . Hot water soluble sesquiterpenes [anhydroperoxy-costunolide and 3-oxoeudesma-1,4(15),11(13)triene-12,6alpha-olide] isolated from laurel (Laurus nobilis L.) induce cell death and morphological change indicative of apoptotic chromatin condensation in.... Oncol Rep. 2003; 11(1):85-8. View

14.

Rasul A, Ding C, Li X, Khan M, Yi F, Ali M . Dracorhodin perchlorate inhibits PI3K/Akt and NF-κB activation, up-regulates the expression of p53, and enhances apoptosis. Apoptosis. 2012; 17(10):1104-19. DOI: 10.1007/s10495-012-0742-1. View

15.

Bergamo A, Gagliardi R, Scarcia V, Furlani A, Alessio E, Mestroni G . In vitro cell cycle arrest, in vivo action on solid metastasizing tumors, and host toxicity of the antimetastatic drug NAMI-A and cisplatin. J Pharmacol Exp Ther. 1999; 289(1):559-64. View

16.

Horwitz S . Taxol (paclitaxel): mechanisms of action. Ann Oncol. 1994; 5 Suppl 6:S3-6. View

17.

Choi Y, Cho S, Woo S, Yun Y, Jo J, Kim W . Saussurea lappa Clarke-Derived Costunolide Prevents TNF α -Induced Breast Cancer Cell Migration and Invasion by Inhibiting NF- κ B Activity. Evid Based Complement Alternat Med. 2013; 2013:936257. PMC: 3755433. DOI: 10.1155/2013/936257. View

18.

Frenzel A, Grespi F, Chmelewskij W, Villunger A . Bcl2 family proteins in carcinogenesis and the treatment of cancer. Apoptosis. 2009; 14(4):584-96. PMC: 3272401. DOI: 10.1007/s10495-008-0300-z. View

19.

Lin Y, Xu J, Liao H, Li L, Pan L . Piperine induces apoptosis of lung cancer A549 cells via p53-dependent mitochondrial signaling pathway. Tumour Biol. 2013; 35(4):3305-10. DOI: 10.1007/s13277-013-1433-4. View

20.

Kim S, Kang S, Kim H, Kim T . Potentiation of 1,25-dihydroxyvitamin D(3)-induced differentiation of human promyelocytic leukemia cells into monocytes by costunolide, a germacranolide sesquiterpene lactone. Biochem Pharmacol. 2002; 64(8):1233-42. DOI: 10.1016/s0006-2952(02)01292-3. View