Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer

Mohammed Sikander, Bilal Hafeez, Shabnam Malik, Abdulrhman Alsayari, Fathi T. Halaweish, Murali Yallapu, Subhash Chauhan, Meena Jaggi

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Article number36594
JournalScientific Reports
Volume6
DOIs
StatePublished - Nov 8 2016

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Uterine Cervical Neoplasms
Neoplasms
MicroRNAs
Nude Mice
Cucurbitacins
cucurbitacin D
Retinoblastoma Protein
myc Genes
Annexin A5
Cyclin D1
G1 Phase
Growth
S Phase
Heterografts
Inhibitory Concentration 50
Cell Cycle
Body Weight
Phosphorylation
Apoptosis
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • General

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Cucurbitacin D exhibits potent anti-cancer activity in cervical cancer. / Sikander, Mohammed; Hafeez, Bilal; Malik, Shabnam; Alsayari, Abdulrhman; Halaweish, Fathi T.; Yallapu, Murali; Chauhan, Subhash; Jaggi, Meena.

In: Scientific Reports, Vol. 6, 36594, 08.11.2016.

Research output: Contribution to journalArticle

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