Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer.
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.
University of Tennessee Health Science Centre, Memphis, TN, 38163, USA.
Mohammed
M
Sikander
University of Tennessee Health Science Centre, Memphis, TN, 38163, USA.
Bilal Bin
BB
Hafeez
University of Tennessee Health Science Centre, Memphis, TN, 38163, USA.
Shabnam
S
Malik
King Khaled University, College of Pharmacy, Box 188, Abha, 61441, Saudi Arabia.
Abdulrhman
A
Alsayari
South Dakota State University, Brookings, SD, 57007, USA.
Fathi T
FT
Halaweish
University of Tennessee Health Science Centre, Memphis, TN, 38163, USA.
Murali M
MM
Yallapu
University of Tennessee Health Science Centre, Memphis, TN, 38163, USA.
Subhash C
SC
Chauhan
University of Tennessee Health Science Centre, Memphis, TN, 38163, USA.
Meena
M
Jaggi
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000096:biosynthesis; D059807:S Phase Cell Cycle Checkpoints / Q000187:drug effects*; D014315:Triterpenes / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays
D009363:Neoplasm Proteins; D014315:Triterpenes; C038105:cucurbitacin D