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The potential effect of Schisandrin-B combination with panitumumab in wild-type and mutant colorectal cancer cell lines: Role of apoptosis and autophagy.
Sana-Eldine, Asmaa O; Abdelgawad, Hanan M; Kotb, Nahla S; Shehata, Nagwa I.
Afiliação
  • Sana-Eldine AO; Egyptian Drug Authority, Giza, Egypt.
  • Abdelgawad HM; Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
  • Kotb NS; Biochemistry Department, Faculty of postgraduate studies for advanced Biotechnology and life sciences, Beni-Suef University, Beni-Suef, Egypt.
  • Shehata NI; Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
J Biochem Mol Toxicol ; 37(5): e23324, 2023 May.
Article em En | MEDLINE | ID: mdl-36808796
Panitumumab is an approved monoclonal antibody for the treatment of colorectal cancer (CRC); however, mutations in EGFR signaling pathway resulted in poor response. Schisandrin-B (Sch-B) is a phytochemical that was suggested to protect against inflammation, oxidative stress, and cell proliferation. The present study aimed to investigate the potential effect of Sch-B on panitumumab-induced cytotoxicity in wild-type Caco-2, and mutant HCT-116 and HT-29 CRC cell lines, and the possible underlying mechanisms. CRC cell lines were treated with panitumumab, Sch-B, and their combination. The cytotoxic effect of drugs was determined by MTT assay. The apoptotic potential was assessed in-vitro by DNA fragmentation and caspase-3 activity. Additionally, autophagy was investigated via microscopic detection of autophagosomes and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) measurement of Beclin-1, Rubicon, LC3-II, and Bcl-2 expression. The drug pair enhanced panitumumab cytotoxicity in all CRC cell lines where IC50 of panitumumab was decreased in Caco-2 cell line. Apoptosis was induced through caspase-3 activation, DNA fragmentation, and Bcl-2 downregulation. Caco-2 cell line treated with panitumumab showed stained acidic vesicular organelles, contrariwise, all cell lines treated with Sch-B or the drug pair displayed green fluorescence indicating the lack of autophagosomes. qRT-PCR revealed the downregulation of LC3-II in all CRC cell lines, Rubicon in mutant cell lines, and Beclin-1 in HT-29 cell line only. Sch-B at 6.5 µM promoted panitumumab-induced apoptotic cell death, in-vitro, via caspase-3 activation and Bcl-2 downregulation, rather than autophagic cell death. This novel combination therapy against CRC, allows the reduction of panitumumab dose to guard against its adverse effects.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Apoptose Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Neoplasias Colorretais / Apoptose Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article