Molecular Biology Reports

, Volume 45, Issue 6, pp 2429–2439 | Cite as

Novel combination of tanshinone I and lenalidomide induces chemo-sensitivity in myeloma cells by modulating telomerase activity and expression of shelterin complex and its associated molecules

  • Raman Kumar
  • Nidhi Gupta
  • Himani
  • Alpana SharmaEmail author
Original Article


Shelterin complex and its associated molecules are imperative for proper functioning and maintenance of human telomeres. These molecules in association with human telomerase have been found altered in most cancers including multiple myeloma thereby proposed them as suitable therapeutic targets. Further, due to aggressive and recurring behavior of myeloma novel, efficacious and safe therapeutic agents for disease prevention are primary requirements for treatment of this disease. This maiden attempt evaluated the anti-proliferative properties of tanshinone I (TanI) alone or in combination with lenalidomide (Len) on myeloma cancer cell lines (RPMI8226 and U226). Further, after drug treatment levels of telomerase activity (TA) and molecular expression (mRNA & protein) of shelterin complex and its associated molecules have also been investigated. Results demonstrated that, TanI significantly inhibited proliferation of myeloma cells in dose and time dependent manner as observed through cytotoxicity assay. Additionally, induction of apoptosis by TanI and in combination with Len was observed in myeloma cells through propidium iodide (PI) staining, annexin V-FITC/PI staining, TUNEL and caspase-3/7 activity assays. Further, drug treatment significantly decreased (p < 0.01) TA and molecular expression of ACD, TERF2IP and TANK1 in comparison to vehicle control (0.1% DMSO) myeloma cells. Thus, this maiden in-vitro study provided initial evidences of therapeutic potential of TanI alone or in combination with chemotherapeutic agent Len as novel anticancer agents in myeloma cells which need further evaluation in future. Lastly, down-regulation of TA and decreased expression of these molecules underscores their potential as plausible therapeutic targets.


Myeloma Tanshinone I Lenalidomide Apoptosis Telomerase Shelterin complex 



Financial assistance to Mr. Raman Kumar as senior research fellow by Indian Council of Medical Research (ICMR), New Delhi, India is acknowledged.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Research involving human participants and/or animals

This article does not contain any study with human participants or animals performed by any of the authors.


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Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Department of BiochemistryAll India Institute of Medical Sciences (AIIMS)New DelhiIndia
  2. 2.Department of BiochemistryNDMC Medical College & Hindu Rao HospitalNew DelhiIndia

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