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A bibenzyl from Dendrobium ellipsophyllum induces apoptosis in human lung cancer cells

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Abstract

Failure of current chemotherapeutic drugs leads to the recurrence of tumor pathology and mortality in lung cancer patients. This study aimed to evaluate the anticancer activity and related mechanisms of 4,5,4′-trihydroxy-3,3′-dimethoxybibenzyl (TDB), a bibenzyl extracted from Dendrobium ellipsophyllum Tang and Wang, in human lung cancer cells. Cytotoxicity of TDB (0–300 µM) in different types of human lung cancer cells (H460, H292 and H23) and human dermal papilla cells (DPCs) was evaluated via MTT viability assay. Selective anticancer activity of TDB against human lung cancer cells was demonstrated with a high IC50 (approximately > 300 µM) in DPCs, while IC50 in human lung cancer H460, H292 and H23 cells was approximately 100 ± 5.18, 100 ± 8.73 and 188.89 ± 8.30 µM, respectively. After treatment with 50 µM of TDB for 24 h, flow cytometry analysis revealed the significant increase of early and late apoptosis with absence of necrosis cell death in human lung cancer cells. The up-regulation of p53, a tumor-suppressor protein, was elucidated in human lung cancer cells treated with 10–50 µM of TDB. Alteration to down-stream signaling of p53 including activation of pro-apoptosis protein (Bcl-2-associated X protein; Bax), reduction of anti-apoptosis (B cell lymphoma 2; Bcl-2 and myeloid cell leukemia 1; Mcl-1) and suppression on protein kinase B (Akt) survival pathway were notified in TDB-treated lung cancer cells. The information obtained from this study strengthens the potential development of TDB as an anticancer compound with a favorable human safety profile and high efficacy.

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Funding

The work was supported by a Research Grant for New Scholar Ratchadaphiseksomphot Endowment Fund Chulalongkorn University. AH would like to thank scholarship of 60/40 Support for Tuition Fee from the Graduate School, Chulalongkorn University.

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Authors and Affiliations

  1. Department of Biochemistry and Microbiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Anirut Hlosrichok, Somruethai Sumkhemthong & Chatchai Chaotham

  2. Departments of Pharmacognosy and Pharmaceutical Botany, Chulalongkorn University, Bangkok, 10330, Thailand

    Boonchoo Sritularak

  3. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Pithi Chanvorachote

  4. Cell-based Drug and Health Products Development Research Unit, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Pithi Chanvorachote & Chatchai Chaotham

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  1. Anirut Hlosrichok
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Hlosrichok, A., Sumkhemthong, S., Sritularak, B. et al. A bibenzyl from Dendrobium ellipsophyllum induces apoptosis in human lung cancer cells. J Nat Med 72, 615–625 (2018). https://doi.org/10.1007/s11418-018-1186-x

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