Original Article

11, 13-Dehydro Lactone Moiety in Gynecologic Cancer Cells


Background: To study the anti-cancer effect of isoalantolactone, a sesquiterpene    lactoneisolated from the roots of Inula heleniumon human gynecologic cancer cells.

Methods: A structure-activity relationship experiment was designed to identify the functional moiety of isoalantolactone for its significant anti-cancer activity. Five gynecologic cancer cell lines were treated with isoalantolactone. Cell proliferation was determined by MTT assay in vitro and cell apoptosis by flow cytometry.

Results: We found isoalantolactone strongly inhibited the cell proliferationofHEC-1, HAC-2, HOC-21, and HeLa cells. Its inhibitory effect was comparable to that of well-known chemotherapeutic agents, cisplatin and taxol. Furthermore, isoalantolactone induced apoptosis in HeLa cells via caspase. On the contrary, its 11, 13-dihydro derivatives had much weaker anti-proliferative activities than the parent compound.

Conclusion: Isoalantolactone exhibited strong anti-proliferative activities and apoptosis-inducing effects on gynecologic cancer cells. The 11, 13-dehydro lactone moiety was critical for its anti-proliferative activity.

1. Siegel RL, Miller KD, Jemal A (2017). Can-cer Statistics, 2017. CA Cancer J Clin,67(1):7-30.
2. Ho JW, Leung YK, Chan CP (2002). Herbal medicine in the treatment of cancer. Curr Med Chem Anticancer Agent, 2(2):209-214.
3. Lee KH (2010). Discovery and development of natural product-derived chemothera-peutic agents based on a medicinal chem-istry approach. J Nat Prod,73(3):500-516.
4. McKinnon R, Binder M, Zupko I, et al (2014). Pharmacological insight into the anti-inflammatory activity of sesquiter-pene lactones from Neurolaena lobata (L.) R.Br. ex Cass. Phytomedi-cine,21(12):1695-701.
5. Ren Y, Yu J, Kinghorn AD (2016). Devel-opment of Anticancer Agents from Plant-Derived Sesquiterpene Lactones. Curr Med Chem,23(23):2397-2420.
6. Babaei G, Aliarab A, Abroon S, et al (2018). Application of sesquiterpene lactone: A new promising way for cancer therapy based on anticancer activity. Biomed Phar-macother,106:239-246.
7. Konishi T, Shimada Y, Nagao T, et al (2002). Antiproliferative sesquiterpene lac-tones from the roots of Inula helenium. Biol Pharm Bull,25(10):1370-2.
8. Weng Z, Gao H, Hu J, et al (2016). Isoalan-tolactone induces autophagic cell death in SKOV(3) human ovarian carcinoma cells via upregulation of PEA-15. Oncol Rep,35(2):833-40.
9. Liu H, Zhang G, Huang J, et al (2016). At-ractylenolide I modulates ovarian cancer cell-mediated immunosuppression by blocking MD-2/TLR4 complex-mediated MyD88/NF-κB signaling in vitro. J Transl Med,14(1):104.
10. van Haaften C, Boot A, Corver WE, et al (2015). Synergistic effects of the sesquit-erpene lactone, EPD, with cisplatin and paclitaxel in ovarian cancer cells. J Exp Clin Cancer Res, 34(1):38.
11. Cantrell CL, Abate L, Fronczek FR, et al (1999). Antimycobacterial eudesmanolides from Inula helenium and Rudbeckia sub-tomentosa. Planta Med, 65(4):351-5.
12. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell,144(5):646-74.
13. Hainaut P, Plymoth A (2013). Targeting the hallmarks of cancer: towards a rational approach to next-generation cancer ther-apy. Curr Opin Oncol,25(1):50-1.
14. Pal HC, Sehar I, Bhushan S, et al (2010). Ac-tivation of caspases and poly (ADP-ribose) polymerase cleavage to induce apoptosis in leukemia HL-60 cells by Inu-la racemosa. Toxicol In Vitro, 24(6):1599-609.
15. Khan M, Ding C, Rasul A, et al (2012). Iso-alantolactone induces reactive oxygen species mediated apoptosis in pancreatic carcinoma PANC-1 cells. Int J Biol Sci,8(4):533-47.
16. Rasul A, Di J, Millimouno FM, et al (2013). Reactive oxygen species mediate isoalan-tolactone-induced apoptosis in human prostate cancer cells. Molecules,18 (8):9382-96.
17. Seo JY, Park J, Kim HJ, et al (2009). Isoalan-tolactone from Inula helenium caused Nrf2-mediated induction of detoxifying enzymes. J Med Food,12(5):1038-45.
18. Di W, Khan M, Rasul A, et al (2014). Iso-alantolactone inhibits constitutive NF-kappaB activation and induces reactive oxygen species-mediated apoptosis in os-teosarcoma U2OS cells through mito-chondrial dysfunction. Oncol Rep,32(4):1585-93.
19. Fan Y, Weng Z, Gao H, et al (2015). Iso-alantolactone Enhances the Radiosensi-tivity of UMSCC-10A Cells via Specific Inhibition of Erk1/2 Phosphorylation. PLoS One,10(2): 0145790.
20. Chen W, Li P, Liu Y, et al (2018). Isoalanto-lactone induces apoptosis through ROS-mediated ER stress and inhibition of STAT3 in prostate cancer cells. J Exp Clin Cancer Res, 37(1): 309.
IssueVol 49 No 11 (2020) QRcode
SectionOriginal Article(s)
DOI https://doi.org/10.18502/ijph.v49i11.4726
Apoptosis; Gynecologic cancer Inulahelenium Isoalantolactone Proliferation

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
How to Cite
LIU Y, MENG Q, JING L, FENG L, ZHOU Z, NI Z. 11, 13-Dehydro Lactone Moiety in Gynecologic Cancer Cells. Iran J Public Health. 49(11):2103-2110.