Swietenolide isolated from Swietenia macrophylla King in Hook seeds shows in vitro anti-colorectal cancer activity through inhibition of mouse double minute 2 (MDM2) homolog

Abstract

Swietenia macrophylla King in Hook (SM) is known to have several medicinal properties. Chloroform extracts of SM seeds (SMCE) as well as two isolated limonoids swietenine (1) and swietenolide (2) showed significant in vitro anti-CRC activity in human colon carcinoma (HCT116) cell line. 2 (IC₅₀ = 5.6 µM) was found to be two times more potent than 1 (IC₅₀ = 10 µM). Both compounds showed anti-CRC activity through inhibition of the Mouse Double Minute 2 homolog (MDM2) of the MDM2-p53 pathway. The Selectivity Index (S.I.) of isolated compounds 1 and 2 for cancer cells were about 6.6 and 12.8 fold respectively which was significantly better than the S.I. of the extract (S.I. ∼1.5).

Graphic Abstract

Keywords:

• Swietenia macrophylla King in Hook
• limonoid
• mouse double minute 2 homolog (MDM2)
• colorectal cancer
• swietenine
• swietenolide

Acknowledgements

Authors are thankful for fellowships (P.C.P. for SRF of NIPER-Kolkata; S.N., D.J., and S.D. for SRF of CSIR), CIF Division of CSIR-IICB for facilities, Mr. Santu Pal, Mr. Soumik Laha, Mr. Sandip Kundu and Dr. E. Padmanabhan of CIF Division for help during data collection and Dr. S. Swarnakar (CSIR-IICB) for useful discussion and suggestions.

Disclosure statement

The authors declare no conflicts of interest.

Dedication

The present work is dedicated to Dr. Snehasikta Swarnakar, Chief Scientist of CSIR-IICB on the occasion of her 60th birth anniversary.

Additional information

Funding

Institutional funding from CSIR-IICB, Kolkata is thankfully acknowledged.