Yehya AHS, Subramaniam AV, Asif M, Kaur G, Abdul Majid AMS, Oon CE. Anti-tumour activity and toxicological studies of combination treatment of Orthosiphon stamineus and gemcitabine on pancreatic xenograft model. World J Gastroenterol 2022; 28(32): 4620-4634 [PMID: 36157930 DOI: 10.3748/wjg.v28.i32.4620]
Corresponding Author of This Article
Chern Ein Oon, PhD, Associate Professor, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Chancellory II, Penang 11800, Malaysia. chern.oon@usm.my
Research Domain of This Article
Integrative & Complementary Medicine
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Aug 28, 2022; 28(32): 4620-4634 Published online Aug 28, 2022. doi: 10.3748/wjg.v28.i32.4620
Anti-tumour activity and toxicological studies of combination treatment of Orthosiphon stamineus and gemcitabine on pancreatic xenograft model
Ashwaq Hamid Salem Yehya, Ayappa V Subramaniam, Muhammad Asif, Gurjeet Kaur, Amin M S Abdul Majid, Chern Ein Oon
Ashwaq Hamid Salem Yehya, Ayappa V Subramaniam, Gurjeet Kaur, Chern Ein Oon, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Penang 11800, Malaysia
Ashwaq Hamid Salem Yehya, Cancer Research, Eman Biodiscoveries, Kedah 08000, Malaysia
Muhammad Asif, Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Punjab 63100, Pakistan
Amin M S Abdul Majid, Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, Australia 2601, Australia
Author contributions: Yehya AHS and Subramaniam AV carried out the experiments; Yehya AHS drafted the manuscript; Yehya AHS, Asif M, and Kaur G analysed the data; Abdul Majid AMS conceived and planned the experiments; Oon CE designed the experiments, derived the model, and supervised the project; All authors have read and approved the final manuscript.
Supported bythe NKEA Research Grant Scheme (NRGS) by the Ministry of Agriculture Malaysia, No. 304/CIPPM/650736/k123.
Institutional animal care and use committee statement: The animal study was approved and conducted under strict guidelines according to USM Animal Ethics Committee (Reference #: USM/Animal Ethics Approval/2016/(97) (746).
Conflict-of-interest statement: Amin Malik Shah Abdul Majid has a commercial interest in C5EOSEW5050ESA O.s extract of NuvastaticTM. All the other authors declare no financial and non-financial competing interests.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chern Ein Oon, PhD, Associate Professor, Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Chancellory II, Penang 11800, Malaysia. chern.oon@usm.my
Received: January 10, 2022 Peer-review started: January 10, 2022 First decision: April 16, 2022 Revised: April 26, 2022 Accepted: June 26, 2022 Article in press: June 26, 2022 Published online: August 28, 2022
ARTICLE HIGHLIGHTS
Research background
Gemcitabine is the cornerstone for pancreatic cancer but demonstrates adverse effects in patients. Orthosiphon stamineus (O.s) has been traditionally used to treat various diseases. C5OSEW5050ESA (NuvastaticTM) is a proprietary extract of O.s that completed a phase 2/3 clinical study for cancer fatigue in cancer patients with solid tumours receiving chemotherapy.
Research motivation
No study has reported the toxicity profile of C5OSEW5050ESA in a pancreatic tumour animal model either as a stand-alone or in combination with gemcitabine.
Research objectives
To determine the anti-tumour activity and potential toxicity of NuvastaticTM and gemcitabine combination on pancreatic xenograft model.
Research methods
Human pancreatic cancer cells were injected subcutaneously into athymic nude mice. C5EOSEW5050ESA (200 or 400 mg/kg per day) was administered orally, while gemcitabine (10 mg/kg/ 3 d) was given intraperitoneally either alone or in combination treatment. Histopathological analyses of key organs, tumour tissues, and incidence of lethality were determined.
Research results
C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment. A comparably greater response in a reduction in tumour growth via a reduction of Ki-67 protein expression, and a decrease in necrosis was also demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination compared to that of individual agents. No signs of organ toxicities were observed in any treatment group.
Research conclusions
The combination of C5EOSEW5050ESA with gemcitabine significantly reduced the pancreatic tumour growth in mice compared to a single treatment. This study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment to gemcitabine for pancreatic cancer.
Research perspectives
Findings from this study may provide the basis for product formulation and manufacturing of botanical drugs (NuvastaticTM) to be used as complementary medicine for the treatment of pancreatic cancer patients.
