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Silencing E6/E7 Oncoproteins in SiHa Cells Treated with siRNAs and Oroxylum indicum Extracts Induced Apoptosis by

Noor Nabilah Talik Sisin1, Aaron Raphael Kong1, Hisham Atan Edinur1

  • 1School of Health Sciences, Universiti Sains Malaysia, 16150, Kota Bharu, Kelantan, Malaysia.

Applied Biochemistry and Biotechnology
|November 3, 2023
PubMed

Insights

Oroxylum indicum extract inhibits human papillomavirus (HPV) oncoproteins E6 and E7 in cervical cancer cells. This leads to the restoration of tumor suppressor proteins p53 and pRb, suggesting potential chemotherapeutic benefits.

Area of Science:

  • Molecular Biology
  • Oncology
  • Pharmacology

Background:

  • Human papillomavirus (HPV) oncoproteins E6 and E7 drive cervical cancer by suppressing tumor suppressor pathways.
  • Targeting p53 and pRb is crucial for blocking HPV-driven malignant transformation.

Purpose of the Study:

  • To investigate the anticancer effects of Oroxylum indicum (OI) methanol extract on SiHa cervical cancer cells.
  • To evaluate the impact of OI extract on apoptosis-related proteins, HPV oncoproteins, and tumor suppressor proteins.

Main Methods:

  • Western blot analysis to assess protein expression (Bcl-2, caspase-3, caspase-9, p53, pRb, E6, E7).
  • Real-time PCR (RT-PCR) to quantify E6/E7 mRNA levels.
  • Treatment with OI extract, gossypin flavonoid, and E6/E7 small interfering RNAs (siRNAs).

Main Results:

  • OI extract inhibited SiHa cell proliferation, increased caspase-3 and caspase-9, and decreased Bcl-2 expression.
  • OI extract suppressed E6/E7 oncoproteins, upregulating p53 and pRb.
  • Combined OI extract and gossypin restored p53 and pRb; OI extract in siRNA-transfected cells further reduced E6/E7 and increased p53/pRb.

Conclusions:

  • OI extract effectively blocks E6/E7-dependent degradation of p53 and pRb in HPV-infected cervical cancer cells.
  • OI extract demonstrates potential as a chemotherapeutic agent for cervical cancer with integrated HPV genomes.
Keywords:
Oroxylum indicumCervical cancerHPVp53pRb

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