Comparative Studies to Evaluate Relative in vitro Potency of Luteolin in Inducing Cell Cycle Arrest and Apoptosis in HaCaT and A375 Cells

Vazhapilly Cijo George,Rangasamy Ashok Kumar,Palamadai Krishnan Suresh,Sanjay Kumar,Devanga Ragupathi Naveen Kumar

doi:10.7314/apjcp.2013.14.2.631

Vazhapilly Cijo George, Rangasamy Ashok Kumar + Show 3 more

Open Access

https://doi.org/10.7314/apjcp.2013.14.2.631

Copy DOI

Abstract

Luteolin is a naturally occurring flavonoid present in many plants with diverse applications in pharmacology. Despite several studies elucidating its significant anti-cancer activity against various cancer cells, the mechanism of action in skin cancer is not well addressed. Hence, we investigated the effects of luteolin in HaCaT (human immortalized keratinocytes) and A375 (human melanoma) cells. The radical scavenging abilities of luteolin were determined spectrophotometrically, prior to a cytotoxic study (XTT assay). Inhibitory effects were assessed by colony formation assay. Further, the capability of luteolin to induce cell cycle arrest and apoptosis were demonstrated by flow cytometry and cellular DNA fragmentation ELISA, respectively. The results revealed that luteolin possesses considerable cytotoxicity against both HaCaT and A375 cells with IC50 values of 37.1 μM and 115.1 μM, respectively. Luteolin also inhibited colony formation and induced apoptosis in a dose and time-dependent manner by disturbing cellular integrity as evident from morphological evaluation by Wright- Giemsa staining. Accumulation of cells in G2/M (0.83-8.14%) phase for HaCaT cells and G0/G1 (60.4-72.6%) phase for A375 cells after 24 h treatment indicated cell cycle arresting potential of this flavonoid. These data suggest that luteolin inhibits cell proliferation and promotes cell cycle arrest and apoptosis in skin cancer cells with possible involvement of programmed cell death, providing a substantial basis for it to be developed into a potent chemopreventive template for skin cancer.

Highlights

Skin cancer accounts for one of the major causes of deaths throughout the world (Girschik et al, 2008; Lo et al, 2011)
The capability of luteolin to induce cell cycle arrest and apoptosis were demonstrated by flow cytometry and cellular DNA fragmentation ELISA, respectively
The results revealed that luteolin possesses considerable cytotoxicity against both HaCaT and A375 cells with IC50 values of 37.1 μM and 115.1 μM, respectively

Summary

Introduction

Skin cancer accounts for one of the major causes of deaths throughout the world (Girschik et al, 2008; Lo et al, 2011). Metastatic melanoma is the most deadly form of skin cancer, developed by the proliferation of transformed melanocytes from the basal region of epidermis. 123,590 new cases of melanoma is diagnosed in United States each year and 8790 people were expected to die which accounts for 65% of all skin cancer deaths (Brady et al, 2011). In India, the incidence of skin malignancies is low, constituting about 1-2% of all the diagnosed cancers (Adinarayan et al, 2011). Despite of this higher incidence rates, efficient/safer treatment still remains critical

Methods

Results

Conclusion