Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer

  • Sci Rep. 2016 Nov 8:6:36594. doi: 10.1038/srep36594.
Mohammed Sikander  1 ,  Bilal Bin Hafeez  1 ,  Shabnam Malik  1 ,  Abdulrhman Alsayari  2 ,  Fathi T Halaweish  3 ,  Murali M Yallapu  1 ,  Subhash C Chauhan  1 ,  Meena Jaggi  1
Affiliations
  • 1. University of Tennessee Health Science Centre, Memphis, TN, 38163, USA.
  • 2. King Khaled University, College of Pharmacy, Box 188, Abha, 61441, Saudi Arabia.
  • 3. South Dakota State University, Brookings, SD, 57007, USA.
PMID: 27824155 DOI: 10.1038/srep36594
Abstract

In this study, we for the first time, investigated the potential anti-cancer effects of a novel analogue of cucurbitacin (Cucurbitacin D) against cervical Cancer in vitro and in vivo. Cucurbitacin D inhibited viability and growth of cervical Cancer cells (CaSki and SiHa) in a dose-dependent manner. IC50 of Cucurbitacin D was recorded at 400 nM and 250 nM in CaSki and SiHa cells, respectively. Induction of Apoptosis was observed in Cucurbitacin D treated cervical Cancer cells as measured by enhanced Annexin V staining and cleavage in PARP protein. Cucurbitacin D treatment of cervical Cancer cells arrested the cell cycle in G1/S phase, inhibited constitutive expression of E6, Cyclin D1, CDK4, pRb, and Rb and induced the protein levels of p21 and p27. Cucurbitacin D also inhibited phosphorylation of STAT3 at Ser727 and Tyr705 residues as well as its downstream target genes c-Myc, and MMP9. Cucurbitacin D enhanced the expression of tumor suppressor MicroRNAs (miR-145, miRNA-143, and miRNA34a) in cervical Cancer cells. Cucurbitacin D treatment (1 mg/kg body weight) effectively inhibited growth of cervical Cancer cells derived orthotopic xenograft tumors in athymic nude mice. These results demonstrate the potential therapeutic efficacy of Cucurbitacin D against cervical Cancer.

Products