Recent Update of Natural Compounds as HIF-1α Inhibitors in Colorectal Carcinoma

Pratibha Pandey,1,2 Sorabh Lakhanpal,3 Danish Mahmood,4 Lalji Baldaniya,5 Han Na Kang,6 Sungho Hwang,7 Sojin Kang,7 Min Choi,7 Seungjoon Moon,7 Shivam Pandey,8 Kamlesh Chaudhary,9 Fahad Khan,10 Bonglee Kim6,7 1Centre for Research Impact & Outcome, Chitkara University Institute of Engineering and Technology, Chitkara University, Rajpura, Punjab, 140401, India; 2Chitkara Centre for Research and Development, Chitkara University, Baddi, Himanchal Pradesh, 174103, India; 3School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India; 4Department of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraydah, 51452, Saudi Arabia; 5Marwadi University Research Center, Department of Pharmaceutical Sciences, Faculty of Health Sciences, Marwadi University, Rajkot, Gujarat, 360003, India; 6KM Convergence Research Division, Korea Institute of Oriental Medicine, Daejeon, Republic of Korea; 7Department of Pathology, College of Korean Medicine, Kyung Hee University, Hoegidong Dongdaemungu, Seoul, 05253, Republic of Korea; 8School of Applied and Life Sciences, Uttaranchal University, Dehradun, Uttarakhand, 248007, India; 9Department of Neurology, National Institute of Medical Sciences, NIMS University Rajasthan, Jaipur, Rajasthan, India; 10Center for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, IndiaCorrespondence: Fahad Khan; Bonglee Kim, Email [email protected]; [email protected]: Hypoxia-inducible factor (HIF)-1 is a transcription factor that regulates the expression of target genes associated with oxygen homeostasis under hypoxic conditions, thereby contributing to tumor development and progression. Accumulating evidence has demonstrated that HIF-1α mediates different biological processes, including tumor angiogenesis, metastasis, metabolism, and immune evasion. Thus, overexpression of HIF-1α is strongly associated with poor prognosis in cancer patients. Natural compounds are important sources of anticancer drugs and studies have emphasized the decisive role of these mediators in modulating HIF-1α. Therefore, the pharmacological targeting of HIF-1α has emerged as a novel cancer therapeutic approach in recent years. The novelty of this review is that it summarizes natural products targeting HIF-1α in colorectal cancer that have not been presented earlier. We studied research publications related to the HIF-1α domain in cancer from 2010 to 2024. However, our main focus was to identify a better targeted approach for colorectal carcinoma management. Our review described HIF-1α role in tumor progression, summarizes the natural compounds employed as HIF-1α inhibitors, and discusses their potential in the development of natural compounds as HIF-1α inhibitors for colorectal cancer treatment.Keywords: HIF-1α, colorectal cancer, natural compounds, inhibitors, hypoxia