Parthenolide Induces Autophagy In Cervical Cancer Through The Modulation Of Autophagy Dependant Signaling PI3K/AKT Pathways

Aiyavu CHINNAIYAN, Rajah Serfogi Government College(Autonomous), India

1 Department of Biochemistry,Rajah Serfogi Government College(Autonomous),Thanjavur- 613005, India.
2 Department of Biochemistry,Bharathidasan University,Tiruchirapalli - 620024, India

Purpose: Autophagy is a major degradative cellular process that involves the delivery of cytoplasmic cargo into lysosomes leading to the formation of autophagosomes. It prevents the spread of cancer by promoting the death of cancerous cells. In the present work, the parthenolide induced autophagy in cervical cancer HeLa cell line was investigated. Methods: MTT assay was performed to evaluate the cytotoxicity of parthenolide and to determine its IC 50 value. The auto fluorescent agent Monodansylcadaverine (MDC) was used as a marker to detect the autophagosome in HeLa cells. After 24hrs treatment with parthenolide, the cell morphology was examined and visualized using fluorescent microscopy. Results: The parthenolide treated cells exhibited green color. MTT assay showed a dramatic loss of viability of cancer cells treated with varying concentrations of parthenolide (0, 2, 4, 6, 8 and 10 µM). Parthenolide (IC50 = 6µM) significantly inhibited the anti-apoptotic Bcl-2 gene expression and simultaneously up regulated the proapoptotic gene Bax and Caspase-3 expressions. Furthermore, Parthenolide induced autophagy in cervical cancer cells through the formation of autophagosomes by activating PTEN gene expression. In addition, it inhibited PI3K/AKT signaling pathways through the expression of autophagy related genes viz. Atg-5, Beclin-1 via suppressing mTOR gene, which is a key regulator of autophagy and apoptosis. Conclusion: Parthenolide can exert anticancer effects by activating autophagy and by inducing apoptosis in HeLa cells through the upregulation of PTEN gene and inhibition of PI3K/AKT signaling. Our results suggest that parthenolide may have potential activity against cervical cancer cells.