Raptinal ameliorates 1,2-dimethylhydrazine-induced colon cancer through p53/Bcl2/Bax/caspase-3-mediated apoptotic events in vitro and in vivo.

Abstract

OBJECTIVES:

Colon carcinoma stands as the most familiar malignancy throughout across the globe. Raptinal induce apoptosis through the alteration of cellular events. Thus, in the present investigation, the anticancer activity of raptinal counter to 1,2-dimethylhydrazine (DMH) persuaded colon carcinoma has been evaluated through both in vivo and in vitro systems.

MATERIALS AND METHODS:

The pharmacophore analysis demonstrated the binding efficacy of raptinal with the apoptotic proteins. The chemotherapeutic activity of raptinal was examined through HT-29 human colorectal cancer (CRC) cell line as well as DMH persuaded CRC in the rat model. The cytotoxicity analysis, flow cytometry, and DAPI analysis have been carried out on HT-29 cell line through in vitro assessment. The colon carcinoma has been induced through DMH administration and subsequently Dextran sulfate sodium treatment in male Wistar rats. After 18 weeks of raptinal treatment, the colon tissues have been investigated for aberrant crypt foci (ACF) count, antioxidant status, histology, immunohistochemical assessment, and apoptotic analysis.

RESULTS:

The raptinal therapy on HT-29 cells demonstrated a substantial % of early apoptosis followed by G0 and G1 phase arrest, which subsequently led to apoptosis. Furthermore, it inhibits ACF development with improved colonic abrasions and structural integrity of colonic mucosa with increased levels of antioxidants, proapoptotic biomarkers including p53, caspase-3, Bax and downstream effects of Bcl-2, tumor necrosis factor (TNF)-α, and interleukin (IL)-6 mutation.

CONCLUSIONS:

These findings indicate the raptinal effectively reduces colon cancer by inducing apoptosis through p53/Bcl2/Bax/caspase-3 pathway and suppressing IL-6, TNF-mediated chronic inflammation in the colon cancer microenvironment.

• Authors: Yongting Lan, Yang Yang, Abhijit Das, Barshana Bhattacharya, Souvik Roy
• Journal: Indian journal of pharmacology (Indian J Pharmacol) 2023 Mar-Apr Vol. 55 Issue 2 Pg. 97-107 ISSN: 1998-3751 [Electronic] India
• PMID: 37313935 (Publication Type: Journal Article)

Chemical References

• raptinal
• 1,2-Dimethylhydrazine
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Caspase 3
• Antioxidants

Topics

• Humans
• Male
• Animals
• Rats
• Rats, Wistar
• 1,2-Dimethylhydrazine (toxicity)
• Tumor Suppressor Protein p53
• bcl-2-Associated X Protein
• Caspase 3
• Colonic Neoplasms (chemically induced, drug therapy)
• Antioxidants
• Carcinoma
• Tumor Microenvironment