Skip to main content

Advertisement

SpringerLink
Log in

In vitro cytotoxic activity of isolated compounds from Malaysian Calophyllum species

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

Cancer is a leading cause of death worldwide. In our continuing search for new anticancer agents, four Malaysian Calophyllum species, namely C. castaneum, C. teysmannii, C. canum, and C. sclerophyllum, had been phytochemically studied to give compounds 1–12. All the isolated compounds were evaluated for their antiproliferative activity against nasopharyngeal (SUNE1, TW01, CNE1, HK1) and breast (HCC38, MDA-MB-231, MDA-MB-468, SKBR3) cancer cell lines via methyl thiazolyl tetrazolium cell viability assay. Among the tested compounds, isodispar B (1) showed a promising dose-dependent and a broad spectrum of cytotoxic effects on all the tested cancer cell lines; in particular, potent inhibitory activities were observed on nasopharyngeal cancer cell lines (SUNE1, TW01, CNE1, HK1), with IC50 values ranging from 3.8 to 11.5 µM. In comparison with 5-fluorouracil as positive control, compound 1 was found to exhibit at least sixfold much higher activity than the standard drug used against the nasopharyngeal cell lines. Compound 1 was later found to induce apoptotic cell death in nasopharyngeal cancer cells, as evidenced by ‘Cell Death Detection’ ELISAPLUS kit, and exhibited good cancer-specific cytotoxicity when tested with noncancerous NP460 cells. Meanwhile, compounds 2–12 displayed moderate to weak activities against the tested cancer cell lines. The findings have highlighted the therapeutic potential of compound 1 against nasopharyngeal cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  • Bayma JC, Arruda MSP, Neto MS (1998) A prenylatedxanthone from the bark of Symphonia globulifera. Phytochemistry 49:1159–1160

    Article  CAS  Google Scholar 

  • Bedoya LM, Beltrán M, Sancho R, Olmedo DA, Sánchez-Palomino S, Olmo E, López-Pérez JL, Muñoz E, Feliciano AS, Alcamí J (2005) 4-Phenylcoumarins as HIV transcription inhibitors. Bioorg Med Chem Lett 15:4447–4450

    Article  CAS  PubMed  Google Scholar 

  • Brahmachari G, Jash SK (2014) Naturally occurring calanolides: an update on their anti-HIV potential and total syntheses. Recent Pat Biotechnol 8:3–16

    Article  CAS  PubMed  Google Scholar 

  • Cragg GM, Newman DJ (2003) Plants as a source of anti-cancer and anti-HIV agents. Ann Appl Biol 143:127–133

    Article  CAS  Google Scholar 

  • Csupor-Löffler B, Hajdú Z, Zupkó I, Molnár J, Forgo P, Vasas A, Kele Z, Hohmann J (2011) Antiproliferative constituents of the roots of Conyza canadiensis. Planta Med 77:1183–1188

    Article  PubMed  Google Scholar 

  • Cuesta-Rubio O, Oubada A, Bello A, Maes L, Cos P, Monzote L (2015) Antimicrobial assessment of resins from Calophyllum Antillanum and Calophyllum Inophyllum. Phytother Res 29:1991–1994

    Article  CAS  PubMed  Google Scholar 

  • Dharmaratne HRW, Napagoda MT, Tennakoon SB (2009) Xanthones from roots of Calophyllum thwaitesii and their bioactivity. Nat Prod Res A: Struct Synth 23:539–545

    Article  CAS  Google Scholar 

  • Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • GLOBOCAN (2012) Cancer incidence and mortality worldwide: IARC CancerBase No. 11. http://globocan.iarc.fr. Accessed 16 July 2015

  • Guilet D, Séraphin D, Rondeau D, Richomme P, Bruneton J (2001) Cytotoxic coumarins from Calophyllum dispar. Phytochemistry 58:571–575

    Article  CAS  PubMed  Google Scholar 

  • Hay AE, Hélesbeux JJ, Duval O, Labaïed M, Grellier P, Richomme P (2004) Antimalarial xanthones from Calophyllum caledonicum and Garcinia vieillardii. Life Sci 75:3077–3085

    Article  CAS  PubMed  Google Scholar 

  • Ito C, Itoigawa M, Furukawa H, Tokuda H, Okuda Y, Mukainaka T, Okuda M, Nishino H (1999) Anti-tumor-promoting effects of 8-substituted 7-methoxycoumarins on Epstein-Barr virus activation assay. Cancer Lett 138:87–92

    Article  CAS  PubMed  Google Scholar 

  • Jain SC, Singh B, Jain R (2001) Antimicrobial activity of triterpenoids from Heliotropium ellipticum. Fitoterapia 72:666–668

    Article  CAS  PubMed  Google Scholar 

  • Kouam SF, Yapna DB, Krohn K, Ngadjui BT, Ngoupayo J, Choudhary MI, Schulz B (2007) Antimicrobial prenylatedanthracene derivatives from the leaves of Harungana madagascariensis. J Nat Prod 70:600–603

    Article  CAS  PubMed  Google Scholar 

  • Lim CK, Subramaniam H, Say YH, Jong VY, Khaledi H, Chee CF (2015) A new chromanone acid from the stem bark of Calophyllum teysmannii. Nat Prod Res 29:1970–1977

    Article  CAS  PubMed  Google Scholar 

  • Lim CK, Tho LY, Lim CH, Lim YM, Shah SAA, Weber JFF (2011) Synthesis and SAR study of prenylatedxanthone analogues as HeLa and MDA-MB-231 cancer cell inhibitors. Lett Drug Des Disc 8:523–528

    Article  CAS  Google Scholar 

  • Lin CM, Huang ST, Lee FW, Kuo HS, Lin MH (2006) 6-Acyl-4-aryl/alkyl-5,7-dihydroxycoumarins as anti-inflammatory agents. Bioorg Med Chem 14:4402–4409

    Article  CAS  PubMed  Google Scholar 

  • López-Pérez JL, Olmedo DA, Olmo E, Vásquez Y, Solís PN, Gupta MP, Feliciano AS (2005) Cytotoxic 4-phenylcoumarins from the leaves of Marila pluricostata. J Nat Prod 68:369–373

    Article  PubMed  Google Scholar 

  • Low SY, Tan BS, Choo HL, Tiong KH, Khoo AS, Leong CO (2012) Suppression of BCL-2 synergizes cisplatin sensitivity in nasopharyngeal carcinoma cells. Cancer Lett 314:166–175

    Article  CAS  PubMed  Google Scholar 

  • Mah SH, Ee GCL, Teh SS, Sukari MA (2015) Calophyllum inophyllum and Calophyllum soulattri source of anti-proliferative xanthones and their structure–activity relationships. Nat Prod Res 29:98–101

    Article  CAS  PubMed  Google Scholar 

  • Mai CW, Pakirisamy P, Tay EF, Subramaniam S, Shamsuddin ZH, Pichika MR (2009) Nasopharyngeal carcinoma cell proliferation and apoptosis induced by the standardised ethanolic extracts of Mucuna bracteata. Malays J Chem 11:143–148

    Google Scholar 

  • Mai CW, Yaeghoobi M, Abd-Rahman N, Kang YB, Pichika MR (2014) Chalcones with electron-withdrawing and electron-donating substituents: anticancer activity against TRAIL resistant cancer cells, structure-activity relationship analysis and regulation of apoptotic proteins. Eur J Med Chem 77C:378–387

    Article  Google Scholar 

  • Morel C, Séraphin D, Teyrouz A, Larcher G, Bouchara JP, Litaudon M, Richomme P, Bruneton J (2002) New and antifungal xanthones from Calophyllum caledonicum. Planta Med 68:41–44

    Article  PubMed  Google Scholar 

  • Oliveira MC, Lemos LMS, de Oliveira RG, Dall’Oglio EL, de Sousa Júnior PT, de Oliveira Martins DT (2014) Evaluation of toxicity of Calophyllum brasiliense stem bark extract by in vivo and in vitro assays. J Ethnopharmacol 155:30–38

    Article  PubMed  Google Scholar 

  • Pedro M, Cerqueira F, Sousa ME, Nascimentoa MSJ, Pinto M (2002) Xanthones as inhibitors of growth of human cancer cell lines and their effects on the proliferation of human lymphocytes in vitro. Bioorg Med Chem 10:3725–3730

    Article  CAS  PubMed  Google Scholar 

  • Plattner RD, Spencer GF, Weisleder D, Kleiman R (1974) Chromanone acids in Calophyllum brasiliense seed oil. Phytochemistry 13:2597–2602

    Article  CAS  Google Scholar 

  • Reutrakul V, Chanakul W, Pohmakotr M, Jaipetch T, Yoosook C, Kasisit J, Napaswat C, Santisuk T, Prabpai S, Kongsaeree P, Tuchinda P (2006) Anti-HIV-1 constituents from leaves and twigs of Cratoxylum arborescens. Planta Med 72:1433–1435

    Article  CAS  PubMed  Google Scholar 

  • Sandjo LP, Foster AJ, Rheinheimer J, Anke H, Opatz T, Thines E (2012) Coumarin derivatives from Pedilanthus tithymaloides as inhibitors of conidial germination in Magnaporthe oryzae. Tetrahedron Lett 53:2153–2156

    Article  CAS  Google Scholar 

  • Saraste A, Pulkki K (2000) Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 45:528–537

    Article  CAS  PubMed  Google Scholar 

  • Shen T, Zhang L, Wang YY, Fan PH, Wang XN, Lin ZM, Lou HX (2012) Steroids from Commiphora mukul display antiproliferative effect against human prostate cancer PC3 cells via induction of apoptosis. Bioorg Med Chem Lett 22:4801–4806

    Article  CAS  PubMed  Google Scholar 

  • Sousa GF, Duarte LP, Alcantara AFC, Silva GDF, Vieira-Filho SA, Silva RR, Oliveira DM, Takahashi JA (2012) New triterpenes from Maytenus robusta: structural elucidation based on NMR experimental data and theoretical calculations. Molecules 17:13439–13456

    Article  CAS  PubMed  Google Scholar 

  • Taher M, Attoumani N, Susanti D, Ichwan SJA, Ahmad F (2010) Antioxidant activity of leaves of Calophyllum rubiginosum. Am J Appl Sci 7:1305–1309

    Article  CAS  Google Scholar 

  • Tan BS, Kang O, Mai CW, Tiong KH, Khoo AS, Pichika MR, Bradshaw TD, Leong CO (2013) 6-Shogaol inhibits breast and colon cancer cell proliferation through activation of peroxisomal proliferator activated receptor gamma (PPARgamma). Cancer Lett 336:127–139

    Article  CAS  PubMed  Google Scholar 

  • Viswanathan MB, Ananthi JDJ, Kumar PS (2012) Antimicrobial activity of bioactive compounds and leaf extracts in Jatropha tanjorensis. Fitoterapia 83:1153–1159

    Article  CAS  PubMed  Google Scholar 

  • Wu YP, Zhao W, Xia ZY, Kong GH, Lu XP, Hu QF, Gao XM (2013) Three new xanthones from the stems of Garcinia oligantha and their anti-TMV activity. Phytochem Lett 6:629–632

    Article  CAS  Google Scholar 

  • Ziegler U, Groscurth P (2004) Morphological features of cell death. News Physiol Sci 19:124–128

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the UTAR Research Fund (Project No. IPSR/RMC/UTARRF/2013-C2/L09). The authors would also like to thank Mr. Tinjan Anak Kuda for authentication of the plant material, and the Cancer and Stem Cell Research Centre of International Medical University (IMU) for technical supports.

Author information

Authors and Affiliations

  1. Faculty of Science, Universiti Tunku Abdul Rahman, Jalan Universiti, Bandar Barat, Kampar, Perak, Malaysia

    Chan Kiang Lim, Subramaniam Hemaroopini, Shu Ying Gan, Siew Mian Loo & Jo Ring Low

  2. Centre for Applied Sciences, Faculty of Applied Sciences, Universiti Teknologi MARA, Jalan Meranek, Kota Samarahan, Sarawak, Malaysia

    Vivien Yi Mian Jong

  3. School of Medicine, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia

    Hsien Chuen Soo

  4. Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia

    Chee Onn Leong

  5. Department of Pharmaceutical Chemistry, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia

    Chun Wai Mai & Chin Fei Chee

Authors
  1. Chan Kiang Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Subramaniam Hemaroopini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Shu Ying Gan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Siew Mian Loo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jo Ring Low
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Vivien Yi Mian Jong
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hsien Chuen Soo
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chee Onn Leong
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Chun Wai Mai
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Chin Fei Chee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chan Kiang Lim.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interests.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lim, C.K., Hemaroopini, S., Gan, S.Y. et al. In vitro cytotoxic activity of isolated compounds from Malaysian Calophyllum species. Med Chem Res 25, 1686–1694 (2016). https://doi.org/10.1007/s00044-016-1606-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-016-1606-y

Keywords

Search

Navigation