Polymolecular botanical drug of Orthosiphon stamineus extract (C5OSEW5050ESA) as a complementary therapy to overcome gemcitabine resistance in pancreatic cancer cells

Ashwaq H S Yehya; Muhammad Asif; Amin M S Abdul Majid; Chern E Oon

doi:10.1016/j.jtcme.2022.10.002

Polymolecular botanical drug of Orthosiphon stamineus extract (C5OSEW5050ESA) as a complementary therapy to overcome gemcitabine resistance in pancreatic cancer cells

J Tradit Complement Med. 2022 Oct 14;13(1):39-50. doi: 10.1016/j.jtcme.2022.10.002. eCollection 2023 Jan.

Authors

Ashwaq H S Yehya^{1

2}, Muhammad Asif³, Amin M S Abdul Majid⁴, Chern E Oon²

Affiliations

¹ Vatche and Tamar Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, 90095, USA.
² Institute for Research in Molecular Medicine (INFORMM), Unversiti Sains Malaysia, Penang, 11800, Malaysia.
³ Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, 63100, Pakistan.
⁴ ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australian National University, 0200, Australia.

Abstract

Background and aim: Gemcitabine remains the cornerstone of pancreatic cancer treatment, despite exhibiting a modest effect on patient survival due to the development of drug resistance. Nuvastatic™ polymolecular botanical drug Orthosiphon stamineus (O. stamineus) is a folklore Asian herbal medicine that is used for the treatment of a variety of ailments. However, little is known about the mechanism of actions of the Nuvastatic™ polymolecular botanical drug of O. stamineus as a complementary therapy in resistant pancreatic cancer. It is postulated that the proprietary O. stamineus extract formulation (ID: C5EOSEW5050ESA) in Nuvastatic™ may sensitise resistant pancreatic cancer cells to gemcitabine. This study was conducted to assess the cytotoxic activity and synergistic effects of C5EOSEW5050ESA in gemcitabine-resistant pancreatic cancer cells.

Experimental procedure: The effects of C5EOSEW5050ESA treatment on cell viability, multidrug-resistant genes, epithelial-mesenchymal transition, cellular senescence, cell death, and Notch signalling pathway were evaluated in gemcitabine-resistant Panc-1 cells.

Results and conclusion: C5EOSEW5050ESA sensitised gemcitabine resistant cells towards C5EOSEW5050ESA-gemcitabine combination treatment by reducing the expression of multidrug-resistant genes and epithelial-mesenchymal transition markers in gemcitabine-resistant cells compared to the control group, possibly through the inhibition of Notch signalling. This study provides valuable insight into using C5EOSEW5050ESA as a potential complementary treatment for resistant pancreatic cancer.