Mechanistic insights on mogrosides as bifunctional regulators of metabolic reprogramming and immune modulation in tumor microenvironment
7 affiliations
- 1School of Health Sciences and Technology (SoHST), UPES, Dehradun, 248007 India
- 2Division of Biotechnology, CSIR-Institute of Himalayan Bioresource Technology, Palampur, India
- 3Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Campus, Ghaziabad, Uttar Pradesh India
- 4Chemistry and Bioprospecting Division, Forest Research Institute, Dehradun, 248006 India
- 5Department of Applied Physics, School of Science, Aalto University, Puumiehenkuja 2, FIN-02150 Espoo, Finland
- 6University Center for Research and Development, Chandigarh University, Mohali, Punjab India
- 7Nanomicroscopy Center, Aalto University, Puumiehenkuja 2, FIN-02150 Espoo, Finland
Abstract
Metabolic reprogramming and immune evasion are interconnected hallmarks of cancer that sustain tumor progression and therapeutic resistance. This review summarizes current mechanistic evidence supporting the therapeutic potential of mogrosides, derived from the fruits of Siraitia grosvenorii, as multi-functional agents with dual roles in regulating tumor metabolism and immune responses. Mechanistically, mogrosides are potent AMPK activators that attenuate the Warburg effect, suppress PI3K/AKT/mTOR signaling, and inhibit de novo lipogenesis. Also, mogrosides suppress lactate accumulation within the tumor microenvironment. In parallel, they modulate immune responses through inhibition of STAT3 and NF-κB signaling pathways, resulting in reduced pro-inflammatory cytokine production and decreased PD-L1 expression. Additionally, mogrosides interfere with oncogenic signaling cascades including JAK/STAT3 and MAPK/ERK that regulate proliferation and survival. They further suppress epithelial–mesenchymal transition and matrix metalloproteinase expression, limiting metastatic potential. By simultaneously targeting metabolic plasticity and immune suppression, mogrosides represent promising adjuvant candidates in cancer therapy; however, further clinical investigations are required to validate their translational potential.
Graphical abstract:
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00262-026-04478-w.
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BibTeX
@article{patial2026mechanistic,
title = {{Mechanistic insights on mogrosides as bifunctional regulators of metabolic reprogramming and immune modulation in tumor microenvironment}},
author = {Meghna Patial and Rohit Joshi and Jyoti Rajput and Vineet Kumar and Janne Ruokolainen and Kavindra Kumar Kesari and Dhruv Kumar},
journal = {Cancer Immunology, Immunotherapy : CII},
year = {2026},
month = jul,
doi = {10.1007/s00262-026-04478-w},
url = {https://doi.org/10.1007/s00262-026-04478-w},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Mechanistic insights on mogrosides as bifunctional regulators of metabolic reprogramming and immune modulation in tumor microenvironment
AU - Meghna Patial
AU - Rohit Joshi
AU - Jyoti Rajput
AU - Vineet Kumar
AU - Janne Ruokolainen
AU - Kavindra Kumar Kesari
AU - Dhruv Kumar
PY - 2026
DA - 2026/07/24
JO - Cancer Immunology, Immunotherapy : CII
DO - 10.1007/s00262-026-04478-w
UR - https://doi.org/10.1007/s00262-026-04478-w
AB - Metabolic reprogramming and immune evasion are interconnected hallmarks of cancer that sustain tumor progression and therapeutic resistance. This review summarizes current mechanistic evidence supporting the therapeutic potential of mogrosides, derived from the fruits of Siraitia grosvenorii, as multi-functional agents with dual roles in regulating tumor metabolism and immune responses. Mechanistically, mogrosides are potent AMPK activators that attenuate the Warburg effect, suppress PI3K/AKT/mTOR signaling, and inhibit de novo lipogenesis. Also, mogrosides suppress lactate accumulation within the tumor microenvironment. In parallel, they modulate immune responses through inhibition of STAT3 and NF-κB signaling pathways, resulting in reduced pro-inflammatory cytokine production and decreased PD-L1 expression. Additionally, mogrosides interfere with oncogenic signaling cascades including JAK/STAT3 and MAPK/ERK that regulate proliferation and survival. They further suppress epithelial–mesenchymal transition and matrix metalloproteinase expression, limiting metastatic potential. By simultaneously targeting metabolic plasticity and immune suppression, mogrosides represent promising adjuvant candidates in cancer therapy; however, further clinical investigations are required to validate their translational potential. Graphical abstract: Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00262-026-04478-w.
SN - 0340-7004
SN - 1432-0851
ER -