Download PDF
CC BY-NC-ND 4.0 · Planta Medica International Open 2022; 9(01): e54-e59
DOI: 10.1055/a-1699-8748
Original Papers

Libocedroquinone: A Promising Anticancer Lead against Lung Cancer from Calocedrus Decurrens

Santhi Subramanyan
1   Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
2   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
,
Varsha Karunakaran
1   Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
2   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
,
Selvakumar Deepika
1   Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
,
Anuja Joseph Gracy
1   Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
2   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
,
Veluthoor Sheeba
3   CoreValleys Herbal Technologies, Kozhikode, India
,
Karchesy Joseph
4   Wood Science and Engineering, Oregon State University, Corvallis, OR, USA
,
Kaustabh Kumar Maiti
1   Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
2   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
,
Ramavarma Luxmi Varma
1   Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
2   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
,
Kokkuvayil Vasu Radhakrishnan
1   Chemical Sciences and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, India
2   Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh, India
› Author Affiliations
› Further Information
   Permissions and Reprints

Abstract

A focus on evaluating anticancer potency of various extracts of the heartwood of Calocedrus decurrens against human lung adenocarcinoma (A549) cell line was performed using in vitro MTT assay. The hexane extract displayed excellent cytotoxic effect, and the phytochemical investigation of the hexane and acetone extracts resulted in the isolation of five major compounds. The structure of the compounds was established as libocedrol (1), thymoquinone (2), libocedroquinone (3), diethylphthalate (4), and (1 R, 2 R, 4 R)-p-menthane-1,2,4-triol (5). Compounds 4 and 5 are reported for the first time from the Calocedrus genus. Compounds 1–3 were evaluated for their cytotoxicity against the lung cancer cell line along with a healthy control. Compound 3 was more potent than other compounds against the A549 cell line with an IC50 of 4.8 µM at 24 h. Moreover, compound 3 exhibited less toxicity with the normal lung fibroblast cell line WI-38. This is the first anticancer study of the species Calocedrus decurrens.

Key words

Calocedrus decurrens - Cupressaceae - libocedroquinone - cytotoxicity - lung cancer

Supplementary Material



Publication History

Received: 08 July 2021
Received: 08 October 2021

Accepted: 09 November 2021

Article published online:
07 February 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 Ibrahim TA, El-Hela AA, El-Hefnawy HM, Al-Taweel AM, Perveen S. Chemical composition and antimicrobial activities of essential oils of some coniferous plants cultivated in Egypt. Iran J Pharm Res 2017; 16: 328-337
    PubMedGoogle Scholar
  • 2 Simpson MG. Evolution and diversity of woody and seed plants. Plant Syst 2010; 129-162
    CrossrefPubMedGoogle Scholar
  • 3 Farjon A. A Monograph of Cupressaceae and Sciadopitys. Richmond, Surrey, UK: Royal Botanic Gardens Press, Kew; 2005
    Google Scholar
  • 4 Long PK, Trang NTP, Averyanov LV, Loc PK. Molecular characterization of Calocedrus rupestris Aver., H.T. Nguyen & L. K. Phan, 2008 (Cupressaceae) based on ITS1 partial sequence. Genet Mol Res 2011; 10: 3702-3711
    CrossrefPubMedGoogle Scholar
  • 5 Yen PL, Wu CL, Chang ST, Huang SL, Chang HT. Antioxidative lignans from phytochemical extract of Calocedrus formosana florin. BioResources 2012; 7: 4122-4131
    CrossrefPubMedGoogle Scholar
  • 6 Chang HT, Cheng YH, Wu CL, Chang ST, Chang TT, Su YC. Antifungal activity of essential oil and its constituents from Calocedrus macrolepis var. formosana Florin leaf against plant pathogenic fungi. Bioresour Technol 2008; 99: 6266-6270
    CrossrefPubMedGoogle Scholar
  • 7 Hsien CL, Tseng MH, Pan RN, Chang JY, Kuo CC, Lee TH, Kuo YH. Labdanecaryophyllic acid, a novel cytotoxic C35 terpenoid from Calocedrus macrolepis var. formosana. Tetrahedron Lett 2011; 52: 515-517
    CrossrefPubMedGoogle Scholar
  • 8 Wu XD, Wang SY, Wang L, He J, Li GT, Ding LF, Gong X, Dong LB, Song LD, Li Y, Zhao QS. Labdane diterpenoids and lignans from Calocedrus macrolepis. Fitoterapia 2013; 85: 154-160
    CrossrefPubMedGoogle Scholar
  • 9 Tsai CC, Chen CJ, Tseng HW, Hua KF, Tsai RY, Lai MH, Chao LK, Chen ST. Cytomic screening of immuno-modulating activity compounds from Calocedrus formosana. Comb Chem High Throughput Screen 2008; 11: 834-842
    CrossrefPubMedGoogle Scholar
  • 10 Hsu KP, Tu SH, Su YC, Ho CL. Chemical composition and antimicrobial activity against food-borne pathogens of Calocedrus formosana heartwood essential oil. Nat Prod Commun 2021; 16: 1-8
    PubMedGoogle Scholar
  • 11 Chiang YM, Liu HK, Lo JM, Chien SC, Chan Y, Lee TH, Su J-K, Kuo Y-H. Cytotoxic constituents of the leaves of Calocedrus formosana. J Chinese Chem Soc 2003; 50: 161-166
    CrossrefPubMedGoogle Scholar
  • 12 Fang JM, Hsu KC, Cheng YS. Lignans from leaves of Calocedrus formosana. Phytochemistry 1989; 28: 3553-3555
    CrossrefPubMedGoogle Scholar
  • 13 Chao KP, Hua KF, Hsu HY, Su YC, Chang ST. Anti-inflammatory activity of sugiol, a diterpene isolated from Calocedrus formosana bark. Planta Med 2005; 71: 300-305
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Zavarin E, Anderson AB. Extractive components from Incense-cedar heartwood (Libocedrus decurrens Torrey) I. Occurrence of carvacrol, hydrothymoquinone, and thymoquinone. J Org Chem 1955; 20: 82-88
    CrossrefPubMedGoogle Scholar
  • 15 Zavarin E, Anderson AB. Extractive components from Incense-cedar heartwood (Libocedrus decurrens Torrey) II. Occurence and synthesis of p-methoxythymol and p-methoxycarvacrol, two new phenolic compounds. J Org Chem 1955; 20: 443-447
    CrossrefPubMedGoogle Scholar
  • 16 Zavarin E, Anderson AB. Extractive components from Incense-cedar heartwood (Libocedrus decurrens Torrey). III. Occurence of libocedrol, a new phenolic ether, and its p-methoxythymol addition complex. J Org Chem 1955; 20: 788-796
    CrossrefPubMedGoogle Scholar
  • 17 Veluthoor S, Li S, Kelsey RG, Dolan MC, Panella NA, Karchesy J. Two new diterpene phenols from Calocedrus decurrans. Nat Prod Commun 2010; 5: 519-522
    PubMedGoogle Scholar
  • 18 Von Rudloff E. The leaf oil terpene composition of Incense cedar and coast redwood. Can J Chem 1981; 59: 285-287
    CrossrefPubMedGoogle Scholar
  • 19 Veluthoor S, Kelsey RG, González Hernández MP, Panella N, Dolan M, Karchesy J. Composition of the heartwood essential oil of Incense cedar (Calocedrus decurrens Torr.). Holzforsch Int J Biol Chem Phys Technol Wood 2011; 65: 333-336
    PubMedGoogle Scholar
  • 20 Garcia G, Tissandie L, Filippi JJ, Tomi F. New pinane derivatives found in essential oils of Calocedrus decurrens. Molecules 2017; 22: 921
    CrossrefPubMedGoogle Scholar
  • 21 Manter DK, Kelsey RG, Karchesy JJ. Antimicrobial activity of extractable conifer heartwood compounds toward Phytophthora ramorum. J Chem Ecol 2007; 33: 2133-2147
    CrossrefPubMedGoogle Scholar
  • 22 Anderson AB, Schcffer TC, Duncan CG. The chemistry of decay resistance and its decrease with heartwood ageing in Incense cedar. Holzforsch Int J Biol Chem Phys Technol Wood 1963; 17: 1-5
    PubMedGoogle Scholar
  • 23 Dolan MC, Dietrich G, Panella NA, Montenieri JA, Karchesy JJ. Biocidal activity of three wood essential oils against Ixodes scapularis (Acari: Ixodidae), Xenopsylla cheopis (Siphonaptera: Pulicidae), and Aedes aegypti (Diptera: Culicidae). J Econ Entomol 2007; 100: 622-625
    CrossrefPubMedGoogle Scholar
  • 24 Moerman DE. Native American Ethnobotany. Oregon: Timber Press; 1998
    Google Scholar
  • 25 Ivankovic S, Stojkovic R, Jukic M, Milos M, Milos M, Jurin M. The antitumor activity of thymoquinone and thymohydroquinone in vitro and in vivo. Exp Oncol 2006; 28: 220-224
    PubMedGoogle Scholar
  • 26 Xuan TD, Chung IM, Khanh TD, Tawata S. Identification of phytotoxic substances from early growth of barnyard grass (Echinochloa crusgalli) root exudates. J Chem Ecol 2006; 32: 895-906
    CrossrefPubMedGoogle Scholar
  • 27 Mahmoud AA, Ahmed AA. α-Pinene-type monoterpenes and other constituents from Artemisia suksdorfii. Phytochemistry 2006; 67: 2103-2109
    CrossrefPubMedGoogle Scholar
  • 28 Hammami S, Elshamy AI, Mokni REl, Snene A, Iseki K, Dhaouadi H, Okamoto Y, Suenaga M, Noji M, Umeyama A, Asakawa Y. Chemical constituents of the aerial parts of Daucus carota subsp. hispidus growing in Tunisia. Nat Prod Commun 2019; 14: 1-6
    PubMedGoogle Scholar
  • 29 Majdalawieh AF, Fayyad MW, Nasrallah GK. Anticancer properties and mechanisms of action of thymoquinone, the major active ingredient of Nigella sativa. Crit Rev Food Sci Nutr 2017; 57: 3911-3928
    CrossrefPubMedGoogle Scholar
  • 30 Ahmad A, Mishra RK, Vyawahare A, Kumar A, Rehman MU, Qamar W, Khan AQ, Khan R. Thymoquinone (2-Isoprpyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: chemistry and biological effects. Saudi Pharm J 2019; 27: 1113-1126
    CrossrefPubMedGoogle Scholar
  • 31 Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells. J Cell Physiol 2019; 234: 10421-10431
    CrossrefPubMedGoogle Scholar
  • 32 Imran M, Rauf A, Khan IA, Shahbaz M, Qaisrani TB, Fatmawati S, Abu-Izneid T, Imran A, Rahman KU, Gondal TA. Thymoquinone: a novel strategy to combat cancer: a review. Biomed Pharmacother 2018; 106: 390-402
    CrossrefPubMedGoogle Scholar
  • 33 Yang J, Kuang XR, Lv PT, Yan XX. Thymoquinone inhibits proliferation and invasion of human nonsmall-cell lung cancer cells via ERK pathway. Tumor Biol 2015; 36: 259-269
    CrossrefPubMedGoogle Scholar
  • 34 Banerjee S, Azmi AS, Padhye S, Singh MW, Baruah JB, Philip PA, Sarkar FH, Mohammad RM. Structure-activity studies on therapeutic potential of thymoquinone analogs in pancreatic cancer. Pharm Res 2010; 27: 1146-1158
    CrossrefPubMedGoogle Scholar
  • 35 Joseph MM, Aravind SR, Varghese S, Mini S, Sreelekha TT. PST-Gold nanoparticle as an effective anticancer agent with immunomodulatory properties. Colloids Surfaces B Biointerfaces 2013; 104: 32-39
    CrossrefPubMedGoogle Scholar
  • 36 Joseph MM, Aravind SR, George SK, Raveendran Pillai K, Mini S, Sreelekha TT. Galactoxyloglucan-modified nanocarriers of doxorubicin for improved tumor-targeted drug delivery with minimal toxicity. J Biomed Nanotechnol 2014; 10: 3253-3268
    CrossrefPubMedGoogle Scholar