Orientin Induces G0/G1 Cell Cycle Arrest and Mitochondria Mediated Intrinsic Apoptosis in Human Colorectal Carcinoma HT29 Cells.

Thangaraj Thangaraj,Balasubramanian Balasubramanian,Natesan Natesan,Park Park,Manju Manju,Liu Liu

doi:10.3390/biom9090418

Abstract

Colorectal carcinoma is one of the utmost diagnosed cancer with a steep increase in mortality rate. The incidence has been increasing in developing countries like India due to a westernization life style. Flavonoids have been explored widely for its various pharmacological activity including antitumor activity. Orientin, an analogue of luteolin (citrus flavonoid) isolated from rooibos and tulsi leaves is also expected to deliver significant antitumor activity similar to that of luteolin. The present study anticipates exploring the antitumor activity of orientin against colorectal carcinoma cells (HT29). Orientin exhibited remarkable cytotoxicity and antiproliferative activity against HT29 cells, which is clearly evident from tetrazolium based cytotoxicity and lactate dehydrogenase release assays. Orientin induce G0/G1 cell cycle arrest and regulates cyclin and cyclin-dependent protein kinases in order to prevent the entry of the cell cycle to the S phase. Annexin V-FITC (V-Fluorescein Isothiocyanate) dual staining reveals the apoptotic induction ability of orientin. The Bcl-2 family proteins along with the inhibitor of apoptotic proteins were regulated and the tumor suppressor p-53 expression have been decreased. In conclusion, our results proposed that orientin could be a potent chemotherapeutic agent against colorectal cancer after ascertaining their molecular mechanisms.

Highlights

Colorectal cancer (CRC) is the third most recurrently diagnosed cancer and fourth most likely cause of cancer mortality worldwide with increasing incidence in recent years [1]
The present study investigates the influence of orientin on proliferation, cell cycle arrest and apoptosis in human CRC cells (HT29) and to explore the underlying mechanisms involved in the pharmacological actions of orientin
Orientin and irinotecan (CPT-11) treated and untreated control HT29 cells were studied for determining the inhibition of cell viability using the tetrazolium based cytotoxicity assay

Summary

Introduction

Colorectal cancer (CRC) is the third most recurrently diagnosed cancer and fourth most likely cause of cancer mortality worldwide with increasing incidence in recent years [1]. Numerous reports have highlighted the role of flavonoids in inducing apoptotic signaling pathways and thereby thwarting the progression of CRC. A meta-analysis reveals that, the increase in consumption of few dietary flavonoids highly correlated with a decreased risk of colon and rectal cancer [4]. Flavonoids such as quercetin, luteolin, kaempferol, apigenin, epigallocatechin, Biomolecules 2019, 9, 418; doi:10.3390/biom9090418 www.mdpi.com/journal/biomolecules

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