The Anti-Proliferative Activity of Anisosciadone: A New Guaiane Sesquiterpene from Anisosciadium lanatum

Author(s): Ahmed A. Mahmoud*, Wael M. El-Sayed*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 19 , Issue 9 , 2019

Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Background: The increase in cancer rate and the development of resistant tumors require a continuous search for new anticancer agents.

Aims: This study aimed to analyze and identify the chemical constituents of Anisosciadium lanatum, and to investigate the antiproliferative activity of the identified constituents against various human cell lines (HepG2, MCF7, HT29, A549, and PC3) along with the possible molecular mechanisms involved.

Methods: The structure of the isolated compounds was determined by spectroscopic techniques including HRFABMS, GC-MS, IR, and 400 MHz 1D and 2D NMR analyses (1H, 13C NMR, DEPT, 1H-1H COSY, HMQC, HMBC and NOESY). The antiproliferative activity and IC50 value of the isolated compounds were measured and compared to doxorubicin.

Results: A new guaiane sesquiterpene containing a rare epoxide structural element, 10β,11β−epoxy−1α,4β,5β,7αΗ- guaiane-9-one, anisosciadone (1), and stigmasterol (2) have been isolated from the plant. Anisosciadone (1) showed a significant antiproliferative activity against liver, colon, and lung cells only, while stigmasterol (2) had a significant activity against liver, colon, and breast cells. Both 1 and 2 caused no cytotoxicity to normal fibroblasts. Anisosciadone elevated the expression and activity of Caspase 3 as well as p53 expression without affecting Caspase 9 in HepG2 cells. It also caused ~ 50% downregulation in cdk1 expression.

Conclusion: Taken together, anisosciadone was specific in action against cancer cells and induced apoptosis in liver cells. It also has a unique feature by elevating the expression and activity of Caspase 3 without affecting the initiator Caspase 9. Therefore, anisosciadone deserves more investigation as a targeted therapy for cancer.

Keywords: Apiaceae, apoptosis, EGFR, p53, Caspases, CDK1.

Sarkhail, P. Traditional uses, phytochemistry and pharmacological properties of the genus Peucedanum: A review. J. Ethnopharmacol., 2014, 156, 235-270.
Sayed-Ahmad, B.; Talou, T.; Saad, Z.; Hijazi, A.; Meraha, O. The Apiaceae: Ethnomedicinal family as source for industrial uses. Ind. Crops Prod., 2017, 109, 661-671.
Jeyabalan, J.; Aqil, F.; Soper, L.; David, J.; Schultz, D.J.; Ramesh, C.; Gupta, R.C. Potent chemopreventive/antioxidant activity detected in common spices of the Apiaceae family. Nutr. Cancer, 2015, 67, 1201-1207.
Martins, N.; Barros, L.; Santos-Buelga, C.; Ferreira, I.C.F.R. Antioxidant potential of two Apiaceae plant extracts: A comparative study focused on the phenolic composition. Ind. Crops Prod., 2016, 79, 188-194.
Amiri, M.S.; Joharchi, M.R. Ethnobotanical knowledge of Apiaceae family in Iran: A review. Avicenna J. Phytomed., 2016, 6, 621-635.
Saleem, F.; Sarkar, D.; Ankolekar, C.; Shetty, K. Phenolic bioactives and associated antioxidant and anti-hyperglycemic functions of select species of Apiaceae family targeting for type 2 diabetes relevant nutraceuticals. Ind. Crops Prod., 2017, 107, 518-525.
Maulidiani, A.; Faridah, K.; Alfi, S.; Khozirah, L.; Nordin, H. Chemical characterization and antioxidant activity of three medicinal Apiaceae species. Ind. Crops Prod., 2014, 55, 238-247.
El-Sayed, W.M.; Hussin, W.A.; Mahmoud, A.A.; AlFredan, M.A. Antimutagenic activities of Anisosciadium lanatum extracts could predict the anticancer potential in different cell lines. Int. J. Pharm. Pharm. Res, 2017, 9, 197-206.
Chaturvedula, V.S.P.; Prakash, I. Isolation of stigmasterol and β-sitosterol from the dichloromethane extract of Rubus suavissimus. Int. J. Curr. Pham. Res, 2012, 1, 239-242.
Denizot, F.; Lang, R. Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability. J. Immunol. Methods, 1986, 89, 271-277.
Ismail, M.A.; Youssef, M.M.; Arafa, R.K.; Al-Shihry, S.S.; El-Sayed, W.M. Synthesis and antiproliferative activity of monocationic arylthiophene derivatives. Eur. J. Med. Chem., 2016, 126, 789-798.
Nishiya, K.; Kimura, T.; Takeya, K.; Itokawa, H. Ssesquiterpenoids and iridoid glycosides from Valeriana fauriei. Phytochemistry, 1992, 31, 3511-3514.
Wang, H-X.; Liu, C-M.; Liu, Q.; Gao, K. Three types of sesquiterpenes from rhizomes of Atractylodes lancea. Phytochemistry, 2008, 69, 2088-2094.
Hanahan, D.; Weinberg, R.A. The hallmarks of cancer. Cell, 2000, 100, 57-70.
Mariaule, G.; Belmont, P. Cyclin-dependent kinase inhibitors as marketed anticancer drugs: Where are we now? A short survey. Molecules, 2014, 19, 14366-14382.
Hochegger, H.; Dejsuphong, D.; Sonoda, E.; Saberi, A.; Rajendra, E.; Kirk, J.; Hunt, T.; Takeda, S. An essential role for Cdk1 in S phase control is revealed via chemical genetics in vertebrate cells. J. Cell Biol., 2007, 178, 257-268.
Bai, J.; Li, Y.; Zhang, G. Cell cycle regulation and anticancer drug discovery. Cancer Biol. Med., 2017, 14, 348-362.
Levine, A.J. p53, the cellular gatekeeper for growth and division. Cell, 1997, 88, 323-331.
Folkman, J. Tumor suppression by p53 is mediated in part by the antiangiogenic activity of endostatin and tumstatin. Sci. STKE, 2006, 354, 35.
Teodoro, J.G.; Evans, S.K.; Green, M.R. Inhibition of tumor angiogenesis by p53: A new role for the guardian of the genome. J. Mol. Med., 2007, 85, 1175-1186.
Schuler, M.; Bossy-Wetzel, E.; Goldstein, J.C.; Fitzgerald, P.; Green, D.R. p53 Induces apoptosis by caspase activation through mitochondrial cytochrome c release. J. Biol. Chem., 2000, 275, 7337-7342.
Ueno, M.; Kakinuma, Y.; Yuhki, K.; Murakoshi, N.; Iemitsu, M.; Miyauchi, T.; Yamaguchi, I. Doxorubicin induces apoptosis by activation of caspase-3 in cultured cardiomyocytes in vitro and rat cardiac ventricles in vivo. J. Pharmacol. Sci., 2006, 101, 151-158.
Shirley, S.H.; Rundhaug, J.E.; Tian, J.; Cullinan-Ammann, N.; Lambertz, I.; Conti, C.J.; Fuchs-Young, R. Transcriptional regulation of estrogen receptor-A by p53 in human breast cancer cells. Cancer Res., 2009, 69, 3405-3414.
Rathos, M.J.; Khanwalkar, H.; Joshi, K.; Manohar, S.M.; Joshi, K.S. Potentiation of in vitro and in vivo antitumor efficacy of doxorubicin by cyclin-dependent kinase inhibitor P276-00 in human non-small cell lung cancer cells. BMC Cancer, 2013, 13, 1-10.
Sharifi, S.; Barar, J.; Hejazi, M.S.; Samadi, N. Doxorubicin changes Bax /Bcl-xL ratio, caspase-8 and 9 in breast cancer cells. Adv. Pharm. Bull., 2015, 5, 351-359.
Soussi, T.; Beroud, C. Assessing TP53 status in human tumours to evaluate clinical outcome. Nat. Rev. Cancer, 2001, 1, 233-240.
Mayer, E.L. Targeting breast cancer with CDK inhibitors. Curr. Oncol. Rep., 2015, 17, 20-24.
Hill, R.; Rabb, M.; Madureira, P.A.; Clements, D.; Gujar, S.A.; Waisman, D.M.; Giacomantonio, C.A.; Lee, P.W. Gemcitabine-mediated tumour regression and p53-dependent gene expression: Implications for colon and pancreatic cancer therapy. Cell Death Dis., 2013, 4, 1-12.
Paul, M.K.; Mukhopadhyay, A.K. Tyrosine kinase-role and significance in cancer. Int. J. Med. Sci., 2004, 1, 101-115.

Rights & PermissionsPrintExport Cite as

Article Details

Year: 2019
Published on: 22 October, 2019
Page: [1114 - 1119]
Pages: 6
DOI: 10.2174/1871520619666190308112732
Price: $65

Article Metrics

PDF: 35
PRC: 1