Combination Treatment of Biochanin A and Atorvastatin Alters Mitochondrial Bioenergetics, Modulating Cell Metabolism and Inducing Cell Cycle Arrest in Pancreatic Cancer Cells

Vilas Desai; Satya Murthy Tadinada; Hoora Shaghaghi; Ross Summer; James C K Lai; Alok Bhushan

doi:10.21873/anticanres.17038

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Combination Treatment of Biochanin A and Atorvastatin Alters Mitochondrial Bioenergetics, Modulating Cell Metabolism and Inducing Cell Cycle Arrest in Pancreatic Cancer Cells

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Peer reviewed

Combination Treatment of Biochanin A and Atorvastatin Alters Mitochondrial Bioenergetics, Modulating Cell Metabolism and Inducing Cell Cycle Arrest in Pancreatic Cancer Cells

Vilas Desai, Satya Murthy Tadinada, Hoora Shaghaghi, Ross Summer, James C K Lai and Alok Bhushan

Anticancer research, Vol.44(6), pp.2307-2323

06/2024

DOI: 10.21873/anticanres.17038

PMID: 38821627

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Abstract

Pancreatic cancer is an aggressive type of cancer, with a dismally low survival rate of <5%. FDA-approved drugs like gemcitabine have shown little therapeutic success, prolonging survival by a mere six months. Isoflavones, such as biochanin A and daidzein, are known to exhibit anti-cancer activity, whereas statins reportedly have anti-proliferative effects. This study investigated the effects of combination treatment of biochanin A and atorvastatin on pancreatic cancer cells. Pancreatic cancer cells AsPC-1, PANC-1, and MIA PaCa-2 were procured from ATCC. The cell viability studies were carried out using MTT & cell count assays. Flow cytometry was used to study cell apoptosis whereas cell metabolism studies were carried out using the Seahorse Mito stress test and XF-PMP assay. The effects of treatment on cell signaling pathways & cell cycle associated proteins were investigated using western blot whereas invasiveness of cancer cells was evaluated using gelatin zymography. The combination treatment decreased the survival and enhanced pro-apoptotic responses compared to single treatments in the pancreatic cancer cells. In PANC-1 cells, the combination treatment decreased invasiveness, reduced expression of activated STAT3 and expression of critical mediators of cell cycle progression. Furthermore, the combination treatment induced a differential inhibition of respiratory complexes in the pancreatic cancer cells. The combination treatment of biochanin A and atorvastatin exerts enhanced anti-cancer effects, inducing apoptosis, down-regulating cell cycle associated proteins and invasiveness in pancreatic cancer cells and merits further investigation for new, improved treatments for pancreatic cancer.

Antineoplastic Combined Chemotherapy Protocols - pharmacology

Apoptosis - drug effects

Atorvastatin - pharmacology

Cell Cycle Checkpoints - drug effects

Cell Line, Tumor

Cell Proliferation - drug effects

Cell Survival - drug effects

Energy Metabolism - drug effects

Genistein - pharmacology

Humans

Mitochondria - drug effects

Mitochondria - metabolism

Pancreatic Neoplasms - drug therapy

Pancreatic Neoplasms - metabolism

Pancreatic Neoplasms - pathology

Signal Transduction - drug effects

Details

Title: Subtitle: Combination Treatment of Biochanin A and Atorvastatin Alters Mitochondrial Bioenergetics, Modulating Cell Metabolism and Inducing Cell Cycle Arrest in Pancreatic Cancer Cells
Creators: Vilas Desai - Thomas Jefferson University
Satya Murthy Tadinada - University of Iowa
Hoora Shaghaghi - Thomas Jefferson University
Ross Summer - Thomas Jefferson University
James C K Lai - Idaho State University
Alok Bhushan - Thomas Jefferson University
Resource Type: Journal article
Publication Details: Anticancer research, Vol.44(6), pp.2307-2323
DOI: 10.21873/anticanres.17038
PMID: 38821627
NLM abbreviation: Anticancer Res
ISSN: 0250-7005
eISSN: 1791-7530
Language: English
Date published: 06/2024
Academic Unit: Internal Medicine
Record Identifier: 9984966789202771

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